Oncology Research 25(6) Abstracts

Return to Oncology Research>

Oncology Research, Vol. 25, pp. 853-861, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14759582767486
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


miR-326 Inhibits Gastric Cancer Cell Growth Through Downregulating NOB1

Sheqing Ji, Bin Zhang, Ye Kong, Fei Ma, and Yawei Hua

Department of General Surgery, Henan Cancer Hospital, Zhengzhou University Cancer Hospital, Zhengzhou, Henan, P.R. China

MicroRNAs (miRNAs) play a crucial role in the development and progression of human cancers, including gastric cancer (GC). The discovery of miRNAs may provide a new and powerful tool for studying the mechanism, diagnosis, and treatment of GC. In this study, we aimed to investigate the role of miR-326 in the development and progression of GC. Quantitative PCR (qPCR) was used to measure the expression level of miR-326 in GC tissues and cell lines. We found that miR-326 was significantly downregulated during GC. In addition, overexpression of miR-326 inhibited GC cell proliferation. Fluorescence-activated cell sorting (FACS) further showed that miR-326 significantly induced GC cell G2/M arrest. Subsequent dual-luciferase reporter assay identified one of the proto-oncogene NOB1 as a direct target of miR-326, and NOB1 can save growth inhibition caused by miR-326. We also confirmed that the growth inhibition caused by miR-326 is associated with AKT pathway activation. Taken together, our results indicate that miR-326 could serve as a potential diagnostic biomarker and therapeutic option for GC in the near future.

Key words: Gastric cancer (GC); miR-326; NOB1; Proliferation; Cell cycle; AKT

Address correspondence to Sheqing Ji, Department of General Surgery, Henan Cancer Hospital, Zhengzhou University Cancer Hospital, No. 127 Dongming Road, Zhengzhou 450003, Henan, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 863-871, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14772315906527
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


CLIC1 Induces Drug Resistance in Human Choriocarcinoma Through Positive Regulation of MRP1

Jinhui Wu and Dongshuang Wang

Department of Obstetrics and Gynecology, People’s Hospital of YuchengYucheng City, Shangdong Province, P.R. China

Chemotherapy is typically used to treat choriocarcinoma. However, a small proportion of this malignancy develops resistance to common chemotherapeutic drugs such as methotrexate (MTX) and floxuridine (FUDR). This study aimed to investigate the role and potential mechanisms of chloride intracellular channel protein 1 (CLIC1) in the development of chemoresistance in choriocarcinoma JeG3 cells. Two chemoresistant sublines were induced from their parental cell line JeG3 through intermittent exposure to MTX (named JeG3/MTX) or FUDR (named JeG3/FUDR). It was found that expression of CLIC1 was significantly higher in the chemoresistant sublines JeG3/MTX and JeG3/FUDR than in their parental cell line JeG3. Knockdown of CLIC1 by specific siRNA significantly increased cell sensitivity to MTX and FUDR in vitro and in vivo. Moreover, the high expression of CLIC1 in chemoresistant sublines was associated with upregulation of multidrug resistance-associated protein 1 (MRP1). Knockdown of CLIC1 decreased the expression of MRP1 accordingly. While reexpression of CLIC1 in the parental cell JeG3 increased its resistance to MTX and FUDR, depletion of MRP1 significantly blunted CLIC1 reexpression-mediated acquirement of chemoresistance in JeG3 cells. In conclusion, our results suggest that CLIC1 may serve as a critical mediator of chemoresistance in human choriocarcinoma JeG3 cells. The CLIC1-mediated chemoresistance is achieved through positive regulation of MRP1. Depletion of either CLIC1 or its downstream MRP1 may be a promising therapeutic strategy concerning reversing the chemoresistance in human choriocarcinoma JeG3 cells.

Key words: Chloride intracellular channel protein 1 (CLIC1); Multidrug resistance-associated protein 1 (MRP1); ChoriocarcinomaChemoresistance; JeG3 cells

Address correspondence to Jinhui Wu, Department of Obstetrics and Gynecology, People’s Hospital of Yucheng, 753 Kaituo Road, Yucheng City, Shangdong Province 251200, P.R. China. Tel: +86-0534-7221712; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 873-878, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14783701102564
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


Silencing of A-Kinase Anchor Protein 4 (AKAP4) Inhibits Proliferation and Progression of Thyroid Cancer

Jiakai Han,1 Wei Gao,1 Dongyue Su, and Yang Liu

Department of Endocrinology, Huaihe Hospital of Henan University, Kaifeng, Henan Province, P.R. China

A-kinase anchor protein 4 (AKAP4), a member of the A-kinase anchor family of proteins, plays a role in tumor development and progression. However, its expression pattern and function in human thyroid cancer remain obscure. Here we examined AKAP4 expression in thyroid cancer cell lines as well as the effects of AKAP4 on the proliferation and metastasis of thyroid cancer cells. We also explored the molecular mechanism by which AKAP4 mediates the metastatic potential of thyroid cancer cells. Our results revealed that the transcript and protein levels of AKAP4 were significantly upregulated in thyroid cancer cell lines. In vitro experiments showed that knockdown of AKAP4 significantly inhibited the proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) process in thyroid cancer cells. Additionally, knockdown of AKAP4 greatly decreased the protein expression of Shh as well as SmoPtc, and Gli-1 in ACT-1 cells. Finally, the in vivo nude mice model confirmed that knockdown of AKAP4 attenuated tumor growth. In conclusion, our findings demonstrated that knockdown of AKAP4 inhibited proliferation and metastasis, likely through suppressing the Shhsignaling pathway, in thyroid cancer cells. Thus, AKAP4 may act as a potential therapeutic target for human thyroid cancer.

Key words: A-kinase anchor protein 4 (AKAP4); Thyroid cancer; Invasion; Epithelial–mesenchymal transition (EMT)

1These authors provided equal contribution to this work.
Address correspondence to Jiakai Han, Department of Endocrinology, Huaihe Hospital of Henan University, No. 115 of Ximen Street, Kaifeng 475000, Henan Province, P.R. China. Tel: +86-0371-2390651; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 879-886, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14785415155643
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


Silencing of LIM and SH3 Protein 1 (LASP-1) Inhibits Thyroid Cancer Cell Proliferation and Invasion

Wei Gao1 and Jiakai Han1

Department of Endocrinology, Huaihe Hospital of Henan University, Kaifeng, Henan Province, P.R. China

LIM and SH3 protein 1 (LASP-1) is a specific focal adhesion protein that was first identified in breast cancer and then reported to be involved in cell proliferation and migration. Many studies have demonstrated the essential role of LASP-1 in cancer progression. However, there have been no studies on the association of LASP-1 with thyroid cancer. In this study, we investigated the expression pattern and biological function of LASP-1 in thyroid cancer. We found that LASP-1 was highly expressed in thyroid cancer tissues and cell lines. LASP-1 silencing had antiproliferative and anti-invasive effects on thyroid cancer cells. Moreover, tumor xenograft experiments showed that LASP-1 silencing suppressed thyroid cancer cell growth in vivo. We also demonstrated that LASP-1 silencing decreased the protein expression of p-PI3K and p-Akt. In conclusion, these findings suggest LASP-1 to be an oncogene and a potential therapeutic target in thyroid cancer.

Key words: LIM and SH3 protein 1 (LASP-1); Proliferation; Migration; Invasion; Thyroid cancer

1These authors provided equal contribution to this work.
Address correspondence to Wei Gao, Department of Endocrinology, Huaihe Hospital of Henan University, No. 8 Baobei Road, Kaifeng 475000, Henan Province, P.R. China. Tel: +86-0371-23906519; Fax: +86-0371-23906519; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 887-895, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14817158982636
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


Knockdown of DDX5 Inhibits the Proliferation and Tumorigenesis in Esophageal Cancer

Zhenchuan Ma,* Jie Feng,† Yurui Guo,‡ Ranran Kong,* Yuefeng Ma,* Liangzhang Sun,* Xiaoping Yang,* Bin Zhou,* Shaomin Li,* Wei Zhang,* Jiantao Jiang,* Jin Zhang,* Zhe Qiao,* Yao Cheng,* Danjie Zha,* and Shiyuan Liu*

*Department of Thoracic Surgery, The Second Affiliated Hospital of Medical School, Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China
†Department of Nephrology, The First Affiliated Hospital of Medical School, Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China
‡Department of Anesthesia, The Second Affiliated Hospital of Medical School, Xi'an Jiaotong University, Xi'an, Shaanxi, P.R. China

DEAD (Asp-Glu-Ala-Asp) box protein 5 (DDX5), a prototypical member of the DEAD/H-box protein family, has been involved in several human malignancies. However, the expression and biological role of DDX5 in esophageal cancer (EC) remain largely unknown. In this study, we examined the role of DDX5 in regulating EC cell proliferation and tumorigenesis and explored its possible molecular mechanism. We found that DDX5 was overexpressed in human EC cell lines. In addition, knockdown of DDX5 significantly inhibited the proliferation of EC cells in vitro and the growth of EC xenografts in vivo. Knockdown of DDX5 also suppressed the migration/invasion and epithelial-to-mesenchymal transition (EMT) phenotype in EC cells. Furthermore, we observed that knockdown of DDX5 inhibited the expression of β-catenin, c-Myc, and cyclin D1 in EC cells. In conclusion, our findings provide the first evidence that siRNA-DDX5 inhibited the proliferation and invasion of EC cells through suppressing the Wnt/β-catenin signaling pathway. Therefore, DDX5 may be a novel potential therapeutic target for the prevention and treatment of EC.

Key words: DEAD (Asp-Glu-Ala-Asp) box protein 5 (DDX5); Esophageal cancer (EC); Proliferation; Invasion

Address correspondence to Ranran Kong, Department of Thoracic Surgery, The Second Affiliated Hospital of Medical School, Xi’an Jiaotong University, 157 West Wu Road, Xi’an, Shaanxi 710004, P.R. China. Tel: +86-029-87679556; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 897-912, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14816352324532
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


Crude Flavonoid Extract of Medicinal Herb Zingibar officinale Inhibits Proliferation and Induces Apoptosis in Hepatocellular Carcinoma Cells

Ayman I. Elkady,*† Osama A. Abu-Zinadah,* and Rania Abd El Hamid Hussein‡§

*Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
†Zoology Department, Faculty of Science, Alexandria University, Alexandria, Egypt
‡Department of Clinical Nutrition, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia
§Gamal Abd El Nasser Hospital, Alexandria, Egypt

There is an urgent need to improve the clinical management of hepatocellular carcinoma (HCC), one of the most common causes of global cancer-related deaths. Zingibar officinale is a medicinal herb used throughout history for both culinary and medicinal purposes. It has antioxidant, anticarcinogenic, and free radical scavenging properties. Previously, we proved that the crude flavonoid extract of Z. officinale (CFEZO) inhibited growth and induced apoptosis in several cancer cell lines. However, the effect of the CFEZO on an HCC cell line has not yet been evaluated. In this study, we explored the anticancer activity of CFEZO against an HCC cell line, HepG2. CFEZO significantly inhibited proliferation and induced apoptosis in HepG2 cells. Typical apoptotic morphological and biochemical changes, including cell shrinkage and detachment, nuclear condensation and fragmentation, DNA degradation, and comet tail formation, were observed after treatments with CFEZO. The apoptogenic activity of CFEZO involved induction of ROS, depletion of GSH, disruption of the mitochondrial membrane potential, activation of caspase 3/9, and an increase in the Bax/Bcl-2 ratio. CFEZO treatments induced upregulation of p53 and p21 expression and downregulation of cyclin D1 and cyclin-dependent kinase-4 expression, which were accompanied by G2/M phase arrest. These findings suggest that CFEZO provides a useful foundation for studying and developing novel chemotherapeutic agents for the treatment of HCC.

Key words: Hepatocellular carcinoma (HCC); Apoptosis; Reactive oxygen species (ROS); Glutathione (GSH); Mitochondrial potential

Address correspondence to Ayman I. Elkady, Department of Biological Sciences, Faculty of Sciences, King Abdulaziz University, Jeddah 21589, Saudi Arabia. Tel: +966-0530676470; Fax: +966-2-6952290; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 913-921, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14792098307036
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


Knockdown of Long Noncoding RNA CCAT2 Inhibits Cellular Proliferation, Invasion, and Epithelial–Mesenchymal Transition in Glioma Cells

Jing Zeng,*1 Tianping Du,1 Yafeng Song,Yan Gao,Fuyan Li,Ruimin Wu,Yijia Chen,Wei Li,Hong Zhou,Yi Yang,and Zhijun Pei

*Department of Infection Control, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei Province, P.R. China
†Department of Neurosurgery, Renmin Hospital, Hubei University of Medicine, Shiyan, Hubei Province, P.R. China
‡Department of PET Center and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei Province, P.R. China

Long noncoding RNA (lncRNA) colon cancer-associated transcript 2 (CCAT2) has been demonstrated to play an important role in diverse tumorigenesis. However, the biological function of lncRNAs in glioma is still unknown. In this study, we found that lncRNA CCAT2 was overexpressed in glioma tissues and cell lines and associated with tumor grade and size. Furthermore, patients with high levels of lncRNA CCAT2 had poorer survival than those with lower levels of lncRNACCAT2. Knocking down lncRNA CCAT2 expression significantly suppressed the glioma cell growth, migration, and invasion, as well as induced early apoptosis of glioma cells in vitro. Moreover, lncRNA CCAT2 regulated epithelial–mesenchymal transition (EMT)-associated gene expression. In conclusion, lncRNA CCAT2 plays an important role in glioma tumorigenesis and progression and may act as a potential biomarker for therapeutic strategy and prognostic prediction.

Key words: Long noncoding RNAs (lncRNAs); Colon cancer-associated transcript 2 (CCAT2); Glioma; Proliferation; Invasion; Epithelial–mesenchymal transition (EMT)

1These authors provided equal contribution to this work.
Address correspondence to Zhijun Pei, Department of PET Center and Institute of Anesthesiology and Pain, Taihe Hospital, Hubei University of Medicine, 32 South Renmin Road, Shiyan City, Hubei Province 442000, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 923-930, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14798241682647
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


Overexpression of Protease Serine 8 Inhibits Glioma Cell Proliferation, Migration, and Invasion via Suppressing the Akt/mTOR Signaling Pathway

Hu-yin Yang, Da-zhao Fang, Lian-shu Ding, Xiao-bo Hui, and Dai Liu

Department of Neurosurgery, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, P.R. China

Protease serine 8 (PRSS8), a serine peptidase, has a widespread expression in normal epidermal cells. Recently, many researchers demonstrated downregulation of PRSS8 in cancer tissues as well as its tumor suppressor role in cancer development. However, the biological functions of PRSS8 in glioma remain unclear. In the current study, we demonstrated a decreased expression of PRSS8 in glioma tissues and cell lines. PRSS8 upregulation inhibited glioma cell proliferation, migration, and invasion. In addition, xenograft experiments showed that PRSS8 overexpression suppressed glioma cell growth in vivo. We also found that upregulated PRSS8 reduced the protein expression levels of p-Akt and p-mTOR in glioma cells. Taken together, our study demonstrated that overexpression of PRSS8 inhibited glioma cell proliferation, migration, and invasion via suppressing the Akt/mTOR signaling pathway. Therefore, PRSS8 may act as a novel therapeutic target for glioma.

Key words: Protease serine 8 (PRSS8); Proliferation; Migration; Invasion; Glioma

Address correspondence to Dai Liu, Department of Neurosurgery, Huai’an First People’s Hospital, Nanjing Medical University, 6 Beijing Road West, Huai’an, 223300 Jiangsu, P.R. China. Tel: +86-0517-84922412; Fax: +86-0517-84922412; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 931-937, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14772424117423
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


Knockdown of Serine Threonine Tyrosine Kinase 1 (STYK1) Inhibits the Migration and Tumorigenesis in Glioma Cells

Jianping Zhou,* Fan Wang,Bingli Liu,Lin Yang,* Xueying Wang,* and Yu Liu*

*Department of Pediatrics, The Second Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an, P.R. China
†Department of Obstetrics and Gynecology, Shaanxi Provincial People’s Hospital, Xi’an, P.R. China
‡Department of General Surgery, The Second Affiliated Hospital, Medical College of Xi’an Jiaotong University, Xi’an, P.R. China

Pediatric glioma is a devastating brain tumor. Serine threonine tyrosine kinase 1 (STYK1) is a member of the protein tyrosine kinase family and plays a significant role in the formation of several malignant tumors. However, the expression pattern and role of STYK1 in glioma are not yet clear. The aim of this study was to investigate the role and molecular mechanism of STYK1 in glioma. The results showed that STYK1 was highly expressed in glioma cell lines. We also found that knockdown of STYK1 inhibited cell proliferation, migration, and invasion in vitro as well as tumorigenesis in vivo. Furthermore, knockdown of STYK1 significantly decreased the expression levels of phosphorylation of PI3K and Akt in glioma cells. Taken together, our data suggest that STYK1 plays an important role in the development and progression of glioma. Therefore, STYK1 may represent a novel therapeutic target for the treatment of glioma.

Key words: Serine threonine tyrosine kinase 1 (STYK1); Glioma; Invasion; PI3K/Akt pathway

Address correspondence to Jianping Zhou, Department of Pediatrics, The Second Affiliated Hospital, Medical College of Xi’an Jiaotong University, 157 Xiwulu Road, Xi’an 710004, P.R. China. Tel: +86-029-87679541; Fax: +86-029-87276092; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 939-946, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14809827856524
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


Histone Acetyltransferase 1 Promotes Cell Proliferation and Induces Cisplatin Resistance in Hepatocellular Carcinoma

Xin Jin,* Shenghua Tian,† and Pingping Li‡

*Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China
†Department of Endocrinology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China
‡Department of Endocrine and Vascular Surgery, Taihe Hospital, Hubei Medical College, Shiyan, Hubei, P.R. China

Hepatocellular carcinoma (HCC) is one of the most common malignant diseases in the world. Mutations, overexpression, and improper recruitment of HATs can lead to tumorigenesis. HAT1 is the first histone acetyltransferase identified and is related with developing HCC, but the mechanism is still unclear. Interestingly, we found that HAT1 was upregulated in HCC patient specimens and showed that its upregulation facilitates HCC cell growth in vitro and in vivo. Moreover, we demonstrated that HAT1 promoted glycolysis in HCC cells and knockdown of HAT1 sensitized HCC cells to apoptotic death induced by cisplatin. Our results suggest that HAT1 might act as an oncogenic protein promoting cell proliferation and inducing cisplatin resistance in HCC, and targeting HAT1 represents a viable strategy for effective treatment of advanced HCC.

Key words: Hepatocellular carcinoma (HCC); Histone acetyltransferase 1 (HAT1); Cell proliferation; Warburg effect; Cisplatin; Drug resistance

Address correspondence to Xin Jin, Department of Digestive Surgical Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1227 Jiefang Road, Wuhan, Hubei 430022, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 947-957, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14791732531006
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


MicroRNA-181b Inhibits Cellular Proliferation and Invasion of Glioma Cells via Targeting Sal-Like Protein 4

Yu Zhou, Yong Peng, Min Liu, and Yugang Jiang

Department of Neurosurgery, Second Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China

MicroRNAs (miRs), a class of noncoding RNAs that are 18–25 nucleotides in length, are able to suppress gene expression by targeting complementary regions of mRNAs and inhibiting protein translation. Recently, miR-181b was found to play a suppressive role in glioma, but the regulatory mechanism of miR-181b in the malignant phenotypes of glioma cells remains largely unclear. In this study, we found that miR-181b was significantly downregulated in glioma tissues when compared with normal brain tissues, and decreased miR-181b levels were significantly associated with high-grade pathology and a poor prognosis for patients with glioma. Moreover, miR-181b was downregulated in glioma cell lines (U87, SHG44, U373, and U251) compared to normal astrocytes. Overexpression of miR-181b significantly decreased the proliferation, migration, and invasion of glioma U251 cells. Sal-like protein 4 (SALL4) was identified as a novel target gene of miR-181b in U251 cells. The expression of SALL4 was significantly upregulated in glioma tissues and cell lines, and an inverse correlation was observed between the miR-181b and SALL4 expression levels in glioma. Further investigation showed that the protein expression of SALL4 was negatively regulated by miR-181b in U251 cells. Knockdown of SALL4 significantly inhibited the proliferation, migration, and invasion of U251 cells, while overexpression of SALL4 effectively reversed the suppressive effects of miR-181b on these malignant phenotypes of U251 cells. In conclusion, our study demonstrates that miR-181b has a suppressive effect on the malignant phenotypes of glioma cells, at least partly, by directly targeting SALL4. Therefore, the miR-181b/SALL4 axis may become a potential therapeutic target for glioma.

Key words: Glioma; MicroRNAs (miRs); Sal-like protein 4 (SALL4); Proliferation; Migration; Invasion

Address correspondence to Yugang Jiang, M.D., Department of Neurosurgery, Second Xiangya Hospital of Central South University, 139 Renmin Road, Changsha, Hunan 410013, P.R. China. Tel: +86-731-85295110; Fax: +86-731-85295110; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 959-965, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14803482769179
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


Overexpression of Forkhead Box L1 (FOXL1) Inhibits the Proliferation and Invasion of Breast Cancer Cells

Jiateng Zhong,*† Haijun Wang,* Jian Yu,‡ Jinghang Zhang,‡ and Hui Wang†§

*Department of Pathology, Xinxiang Medical University, Xinxiang, P.R. China
†Collaborative Innovation Center of Molecular Diagnosis and Laboratory Medicine in Henan Province, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, P.R. China
‡Department of Pathology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang, P.R. China
§Research Center for Immunology, School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, P.R. China

Forkhead box L1 (FOXL1) is a member of the Forkhead box (FOX) superfamily and was reported to be dysregulated in various types of cancers. However, its expression pattern and underlying cellular function in breast cancer remain largely unexplored. Thus, the aim of this study was to detect FOXL1 expression in breast cancer and to analyze its role in the progression of breast cancer. Our results demonstrated that FOXL1 expression at both the mRNA and protein levels was downregulated in breast cancer tissues and cell lines. Ectopic FOXL1 suppressed breast cancer cell proliferation, migration, and invasion in vitro. Furthermore, overexpression of FOXL1 significantly attenuated tumor growth in breast xenograft models in vivo. Finally, overexpression of FOXL1 significantly downregulated the protein expression levels of β-catenin, c-Myc, and cyclin D1 in MDAMB-231 cells. Taken together, the present study demonstrated that FOXL1 inhibited the proliferation, invasion, and migration of breast cancer in vitro and breast tumor growth in vivo through deactivating the Wnt/β-catenin signaling pathway. Thus, these findings suggest that FOXL1 may be a potential novel target for breast cancer therapy.

Key words: Forkhead box L1 (FOXL1); Breast cancer; Proliferation; Invasion

Address correspondence to Hui Wang, Research Center for Immunology, School of Basic Medical Sciences, Xinxiang Medical University, No. 601 Jinhui Road, Xinxiang 453003, P.R. China. Fax: +86-0373-3029248; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 967-974, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14803476672380
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


miR-107 Promotes Proliferation and Inhibits Apoptosis of Colon Cancer Cells by Targeting Prostate Apoptosis Response-4 (Par4)

Fen Liu,*† Shaojun Liu,* Feiyan Ai,*† Decai Zhang,*† Zhiming Xiao,* Xinmin Nie,‡ and Yunfeng Fu§

*Department of Gastroenterology, The Third Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China
†Hunan Key Laboratory of Nonresolving Inflammation and Cancer, Changsha, Hunan, P.R. China
‡ Clinical Laboratory of The Third Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China
§The Third Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China

Colorectal cancer (CRC) is one of the most common malignancies in the world, with a high incidence and a high mortality. However, the pathogenesis of CRC carcinogenesis is still unexplored. In this study, we investigated the role of miR-107 in the regulation of CRC cell proliferation and apoptosis. First, the expression of miR-107 was observed to be aberrantly increased in human CRC tumor tissues and cell lines when compared to the colonic control tissues and colon epithelial cells. Further study showed that the proliferative and apoptotic capacities of human CRC SW480 and LoVo cells were aberrantly regulated by miR-107. The proliferation of SW480 and LoVo cells was remarkably enhanced by the miR-107 mimic but suppressed by the miR-107 inhibitor when compared to the negative control. On the contrary, the apoptotic rate of both SW480 and LoVo cells was significantly inhibited by miR-107 overexpression but increased by miR-107 inhibition. In addition, we identified prostate apoptosis response-4 (Par4) as a direct target of miR-107 with a potential binding site on the 3′-UTR of mRNA, as evaluated by bioinformatics prediction and luciferase reporter assay. Par4 expression levels were significantly inhibited by the miR-107 mimic but upregulated by the miR-107 inhibitor in both SW480 and LoVo cells. Compared to the control, the increase in Par4 expression significantly inhibited the induction role of miR-107 in the proliferation of SW480 and LoVo cells, and the apoptotic rate of cells repressed by the miR-107 mimic was also reversed by Par4 overexpression. In summary, our results demonstrated that miR-107 exerts a positive role in the survival of CRC cells by directly targeting Par4. This might reveal a novel understanding about human CRC pathogenesis.

Key words: miR-107; Prostate apoptosis response-4 (Par4); Colorectal cancer (CRC); Proliferation; Apoptosis

Address correspondence to Xinmin Nie, The Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha 410013, Hunan Province, P.R. China. Tel: +86-0731-88638888; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Yunfeng Fu, The Third Xiangya Hospital of Central South University, No. 138 Tongzipo Road, Yuelu District, Changsha 410013, Hunan Province, P.R. China. Tel: +86-0731-88638888; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 975-988, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14791726591124
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


MicroRNA-98 Plays a Suppressive Role in Non-Small Cell Lung Cancer Through Inhibition of SALL4 Protein Expression

Wenliang Liu,* Peng Xiao,† Han Wu,* Li Wang,* Demiao Kong,* and Fenglei Yu*

*Department of Thoracic Surgery, Second Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China
†Department of Thoracic Surgery, Third Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China

MicroRNAs (miRs) have been demonstrated to be significantly associated with the development and progression of non-small cell lung cancer (NSCLC). However, the underlying mechanism of miR-98 in mediating the malignant phenotypes of NSCLC cells remains obscure. In this study, we found that miR-98 was significantly downregulated in NSCLC tissues compared to nontumor lung tissues. Downregulation of miR-98 was significantly associated with poor differentiation and advanced clinical stage. Restoration of miR-98 expression significantly decreased the proliferation, migration, and invasion of NSCLC A549 and H1229 cells. SALL4 was identified as a target gene of miR-98, and the protein expression of SALL4 was negatively regulated by miR-98 in NSCLC A549 and H1229 cells. Overexpression of SALL4 promoted A549 and H1229 cell proliferation, migration, and invasion and reversed the suppressive effects of miR-98 on the malignant phenotypes of A549 and H1229 cells. Moreover, SALL4 was found to be significantly upregulated in NSCLC tissues compared to the nontumor lung tissues. We then observed an inverse correlation between the miR-98 and SALL4 levels in NSCLC tissues. In vivo study revealed that miR-98 overexpression suppressed NSCLC growth. In summary, we demonstrate that miR-98 acts as a tumor suppressor in NSCLC cells by inhibiting the protein expression of its target gene SALL4. Therefore, our study highlights the importance of the miR-98/SALL4 axis in NSCLC.

Key words: MicroRNAs (miRs); Non-small cell lung cancer (NSCLC); Tumor suppressor; SALL4

Address correspondence to Wenliang Liu, M.D., Associate Professor, Department of Thoracic Surgery, Second Xiangya Hospital of Central South University, 139 Renmin Middle Road, Changsha 410011, Hunan, P.R. China. Tel: +86-731-85295104; Fax: +86-731-85295104; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 989-999, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14813867762123
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


MicroRNA-373 Promotes Growth and Cellular Invasion in Osteosarcoma Cells by Activation of the PI3K/AKT–Rac1–JNK Pathway: The Potential Role in Spinal Osteosarcoma

Yufeng Liu,* Zhengliang Cheng,† Feng Pan,‡ and Weigang Yan§

*Spinal Surgery Dept1, Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province, Zhengzhou, P.R. China
†The First Department of Orthopedics, Ankang Hospital of Traditional Chinese Medicine, Ankang, P.R. China
‡Department of Acupuncture and Physiotherapy, Maternal and Child Health Care of ZaozhuangZaozhuang, P.R. China
§Spinal Surgery Dept4, Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province, Luoyang, P.R. China

Spinal osteosarcoma (OS) has been proven to be more difficult to treat owing to potently malignant metastasis. The present study aimed to explore the functional role of microRNA (miR)-373 in cell growth and invasion of OS cells, as well as its underlying mechanism. The expression of miR-373 was analyzed in spinal OS tissues and cell lines. MG-63 cells were transfected with the miR-373 mimic or inhibitor and/or treated with the phosphoinositide 3-kinase (PI3K) (LY294002) inhibitor or Ras-related C3 botulinum toxin substrate 1 (Rac) guanosine triphosphate (GTPase) (NSC23766) inhibitor, and then the impact of miR-373 aberrant expression on cell growth and invasion was measured, along with the impact of overexpressing miR-373 on the expression of p53 and PI3K/AKT pathway-related proteins. We found that miR-373 was specifically upregulated in spinal OS tissues p < 0.01) and OS cell lines ( p < 0.01 or p < 0.001). Moreover, miR-373 expression was significantly associated with TNM stage p = 0.035) and tumor size ( p = 0.002). Overexpression of miR-373 promoted MG-63 cell viability, migration, invasion, and colony formation (all p < 0.05), while silencing of miR-373 and LY294002 exerted the opposite effects. Additionally, miR-373 overexpression downregulated p53 as well as its downstream targeted genes and orderly activated the PI3K/AKT–Rac1–JNK signaling pathway. In conclusion, miR-373 promotes growth and cellular invasion in OS cells by activating the PI3K/AKT–Rac1–JNK pathway. Therefore, miR-373 might be a candidate for molecular targeted therapy of spinal OS.

Key words: MicroRNA-373 (miR-373); Metastasis; Spinal osteosarcoma (OS); p53; PI3K/AKT–Rac1–JNK pathway

Address correspondence to Weigang Yan, Spinal Surgery Dept4, Luoyang Orthopedic Hospital of Henan Province, Orthopedic Hospital of Henan Province, No. 82 Qiming South Road, Luoyang 471002, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1001-1008, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14796039599926
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


Overexpression of RAS-Association Domain Family 6 (RASSF6) Inhibits Proliferation and Tumorigenesis in Hepatocellular Carcinoma Cells

Nan Zhu,1 Mahui Si,1 Ning Yang, Yingying Jing, Yong Fu, Xijun Zhao, Zhipeng Lin, and Guangshun Yang

Hepatic Surgery Department, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, P.R. China

Ras-association domain family 6 (RASSF6), a member of the RASSF family, is frequently downregulated in various types of cancer. However, the roles of RASSF6 in human hepatocellular carcinoma (HCC) are still unclear. In this study, we investigated the biological functions and related molecular mechanisms in HCC. Our results found that RASSF6 is expressed in low amounts in HCC tissues and cell lines. Overexpression of RASSF6 obviously inhibited the proliferation, invasion, and EMT process in HCC cells. Furthermore, overexpression of RASFF6 greatly downregulated the protein levels of phosphorylated focal adhesion kinase (FAK), MMP-2, and MMP-9 in HepG2 cells. Last, overexpression of RASFF6 significantly attenuated tumor growth in Balb/c nude mice. In conclusion, the present study revealed that RASFF6 can inhibit the proliferation, invasion, and migration of HCC cells both in vivo and in vitro. These inhibitory effects are through suppressing FAK phosphorylation, leading to decreased MMP-2/9 expression. RASFF6 is therefore a potential therapeutic target for treating HCC.

Key words: Ras-association domain family 6 (RASSF6); Hepatocellular carcinoma (HCC); Invasion; Focal adhesion kinase (FAK) pathway

1These authors provided equal contribution to this work.
Address correspondence to Guangshun Yang, Hepatic Surgery Department, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, No. 225 Changhai Road, Shanghai 200438, P.R. China. Tel: +86-021-65564166; Fax: +86-021-65562400; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1009-1019, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14813859905646
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


miRNA-214 Inhibits Cellular Proliferation and Migration in Glioma Cells Targeting Caspase 1 Involved in Pyroptosis

Zhenfeng Jiang,*1 Lifen Yao,†1 Hongge Ma,† Panpan Xu,† Zhiyan Li,† Mian Guo,‡ Jianhang Chen,* Hongbo Bao,§ Shupei Qiao,¶ Yufang Zhao,¶ Jia Shen,# Minwei Zhu,* Carolyn Meyers,** Guizhen Ma,†† Chuncheng Xie,* Li Liu,* Haiyang Wang,* Wang Zhang,* Qi Dong,† Hong Shen,* and Zhiguo Lin*

*Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China
†Department of Neurology, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China
‡Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, P.R. China
§Department of Neurosurgery, Harbin Medical University Cancer Hospital, Harbin, P.R. China
¶Bio-X Center, School of Life Science and Technology, Harbin Institute of Technology, Harbin, P.R. China
#Orthopedic Hospital Research Center, University of California, Los Angeles, CA, USA
**Department of Pathology and Laboratory Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA
††Department of Operating Room, The First Affiliated Hospital of Harbin Medical University, Harbin, P.R. China

Pyroptosis is a type of proinflammatory programmed cell death mediated by caspase 1 activity and occurs in several types of eukaryotic tumor cells, including gliomas. MicroRNAs (miRNAs), small endogenous noncoding RNAs, have been demonstrated to be advantageous in glioma therapy. However, the question of whether miRNAs regulate pyroptosis in glioma remains unknown. The current study found that caspase 1 expression was substantially increased in both glioma tissues and glioma cell lines, U87 and T98G, while miR-214 expression was significantly downregulated. Luciferase reporter assay recognized caspase 1 as a target gene of miR-214. These findings demonstrate that miR-214 could inhibit cell proliferation and migration through the regulation of pyroptosis intermediated by caspase 1 in glioma U87 and T98G cells and may suggest a novel therapeutic for the intervention of glioma.

Key words: miR-214; Pyroptosis; Caspase 1; Glioma

1These authors provided equal contribution to this work as first authors.
Address correspondence to Lifen Yao, Department of Neurology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, Heilongjiang Province 150001, P.R. China. Tel: +86-451-85555803; Fax: +86-451-53670428; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Zhiguo Lin, Department of Neurosurgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, Heilongjiang Province 150001, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1021-1026, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14821477992177
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


Silencing Transmembrane Protein 45B (TNEM45B) Inhibits Proliferation, Invasion, and Tumorigenesis in Osteosarcoma Cells

Yan Li,1 Wei Guo,1 Shen Liu, Bin Zhang, Bing-Bing Yu, Bo Yang, Shun-Li Kan, and Shi-Qing Feng

Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, P.R. China

Transmembrane protein 45B (TMEM45B) is a member of the TMEM family of proteins and has been reported to be expressed abnormally in different kinds of human tumors. However, the biological function of TMEM45B in osteosarcoma remains unclear. The objective of this study was to investigate the role of TMEM45B in regulating the biological behavior of osteosarcoma cells. Our results demonstrated that the expression of TMEM45B at both the protein and mRNA levels was dramatically upregulated in human osteosarcoma cell lines. Knockdown of TMEM45B significantly suppressed the proliferation, migration, and invasion of U2OS cells in vitro. Mechanistically, knockdown of TMEM45B sharply downregulated the expression level of β-catenin, cyclin D1, and c-Myc in U2OS cells. Finally, knockdown of TMEM45B attenuated tumor growth in transplanted U2OS-derived tumors in nude mice. Taken together, our results demonstrated that TMEM45B plays an important role in regulating the proliferation, migration, and invasion of osteosarcoma cells and that its effects on proliferation and invasion were mediated partially through the Wnt/β-catenin signaling pathway. These observations support our belief that TMEM45B may serve as an oncogene in the development and progression of osteosarcoma.

Key words: Transmembrane protein 45B (TMEM45B); Osteosarcoma; Invasion; Wnt/β-catenin pathway

1These authors provided equal contribution to this work.
Address correspondence to Shi-Qing Feng, Department of Orthopedics, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, P.R. China. Tel: +86-022-60361301; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 1027-1037, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14822800040451
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved


Long Noncoding RNA GAS5 Suppresses Tumorigenesis by Inhibiting miR-23a Expression in Non-Small Cell Lung Cancer

Yongcheng Mei,* Jinchun Si,† Yun Wang,‡ Zhuangshi Huang,§ Haiwen Zhu,* Shijun Feng,* Xuezhi Wu,* and Liwen Wu*

*Department of Cardiothoracic and Vascular Surgery, Zhumadian Central Hospital, Zhumadian, P.R. China
†Department of Surgery, Shangqiu Medical College, Shangqiu, P.R. China
‡Department of Respiratory, Zhumadian Central Hospital, Zhumadian, P.R. China
§Department of Thoracic Surgery, The Second Hospital Affiliated to Zhengzhou University, Zhengzhou, P.R. China

Previous studies reported that elevated expression of long noncoding RNA (lncRNA) GAS5 led to the arrest of non-small cell lung cancer (NSCLC) cell growth and a promotion of apoptosis both in vitro and in vivo. However, its underlying molecular mechanism in NSCLC is still unclear. In the present study, we noted that GAS5 was downregulated in NSCLC tissues and cells and was negatively correlated with miR-23a expression. Luciferase reporter assay and qRT-PCR analysis demonstrated that GAS5 directly interacted with miR-23a and reversely regulated its expression. miR-23a overexpression markedly promoted NSCLC cell proliferation and invasion, while GAS5 overexpression dramatically inhibited NSCLC cell proliferation and invasion and promoted apoptosis. Functional analysis indicated that miR-23a overexpression significantly abolished GAS5 overexpression-induced inhibition of proliferation and invasion, as well as promotion of apoptosis in NSCLC cells. Moreover, xenograft experiments further revealed that upregulation of GAS5 notably impaired the growth of transplanted tumors by suppressing miR-23a in nude mice. These results suggested that overexpression of lncRNAGAS5 inhibits tumorigenesis of NSCLC by inhibiting miR-23a in vitro and in vivo, providing a potential therapeutic strategy for patients with NSCLC.

Key words: Long noncoding RNA (lncRNA); GAS5; Proliferation; Invasion; Apoptosis; miR-23a; Non-small cell lung cancer (NSCLC)

Address correspondence to Yongcheng Mei, Department of Cardiothoracic and Vascular Surgery, Zhumadian Central Hospital, 747 Zhonghua Road, Zhumadian 463000, P.R. China. Tel: +86-13783961828; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it