Oncology Research 26(4) Abstracts

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Oncology Research, Vol. 26, pp. 519-528, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15000757094686
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


miR-103 Functions as a Tumor Suppressor by Directly Targeting Programmed Cell Death 10 in NSCLC

Dong Yang, Jian-Jun Wang, Jin-Song Li, and Qian-Yu Xu

Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, P.R. China

Non-small cell lung cancer (NSCLC) accounts for about 85% of all lung cancer cases. Absence of miR-103 has recently been identified to be associated with metastatic capacity of primary lung tumors. However, the exact role of miR-103 in NSCLC and the molecular mechanism are unclear. In the present study, we showed that miR-103 expression was reduced in NSCLC tissues and cells. miR-103 expression was negatively correlated with tumor size and stage. The overall survival was longer in patients with higher miR-103 level than in those with lower miR-103 expression. miR-103 inhibited cell proliferation in A549 cells, decreased tumor weight and volume, and prolonged survival of tumor-implanted nude mice. miR-103 increased apoptotic cell death in A549 cells. Furthermore, miR-103 decreased the invasion and migration abilities in A549 cells, as evidenced by Transwell and wound healing results. Downregulation of miR-103 significantly reduced the level of programmed cell death 10 (PDCD10). We found a significant decrease in the relative luciferase activity of the reporter gene in A549 cells cotransfected with the miR-103 mimic and pGL3-PDCD10 WT 3′-UTR, but not pGL3-PDCD10 mut 3′-UTR. We showed that overexpression of PDCD10 significantly inhibited miR-103-induced inhibition of cell proliferation, increased apoptosis, and decreased invasion and migration in A549 cells. Moreover, we found that PDCD10 expression was increased in NSCLC tissues and cells. PDCD10 expression was positively correlated with tumor size and stage. Overexpression of PDCD10 increased cell proliferation and inhibited apoptosis in A549 cells. The data demonstrated that dysregulation of the miR-103/ PDCD10 signal may be a novel therapeutic target for the treatment of NSCLC.

Key words: MicroRNA-103 (miR-103); Programmed cell death 10 (PDCD10); Non-small cell lung cancer (NSCLC); Proliferation; Apoptosis

Address correspondence to Jian-Jun Wang, Department of Thoracic Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 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. 26, pp. 529-536, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14972679378357
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


MicroRNA-539 Inhibits the Epithelial–Mesenchymal Transition of Esophageal Cancer Cells by Twist-Related Protein 1-Mediated Modulation of Melanoma-Associated Antigen A4

Zhili Cao,*1 Xiang Zheng,†1 Lei Cao,* and Naixin Liang*

*Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, P.R. China
†Department of Cardiothoracic Surgery, People’s Hospital of Beijing Daxing District, Beijing, P.R. China

MicroRNAs (miRs) play key roles in cancers, yet the potential molecular mechanisms of miR-539 on esophageal squamous cell carcinoma (ESCC) are not well understood. Utilizing informatics screening, Twist-related protein 1 (TWIST1) was hypothesized to be a possible target gene of miR-539. Since the melanoma-associated antigen (MAGE) A4 is reported to be upregulated by TWIST1, this study aimed to examine the biological functions and mechanism involving TWIST1 and MAGE4 of miR-539 in ESCC. miR-539 mimics or scrambled miRs were transfected into human ESCC TE3 cells to interfere with the expression of miR-539. Then qRT-PCR and Western blot analyses were performed to determine the expression levels of epithelial–mesenchymal transition (EMT)-related factors at mRNA and protein levels. The association between miR-539 and TWIST1 as well as TWIST1 and MAGEA4 was evaluated. The connection of miR-539 and TWIST1–MAGEA4 during the EMT progress of ESCC was also explored. Our data demonstrated that miR-539 inhibited the EMT of TE3 cells by downregulating TWIST1, and TWIST1 was a target of miR-539. Moreover, MAGEA4 was positively correlated with TWIST1, and its knockdown inhibited EMT in TE3 cells. Collectively, miR-539 could inhibit EMT in TE3 cells through TWIST1-mediated regulation of MAGEA4. All these findings suggested that miR-539 may be involved in the progression of ESCC and could be a new therapeutic target for this disease.

Key words: Esophageal cancer; miR-539; TWIST1–MAGEA4; Epithelial–mesenchymal transition (EMT)

1These authors provided equal contribution to this work.
Address correspondence to Naixin Liang, Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, No. 1 ShuaifuyuanDongcheng District, Beijing 100730, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 537-546, 2018
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DOI: https://doi.org/10.3727/096504017X
15009792179602
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


Long Noncoding RNA Urothelial Carcinoma-Associated 1 Promotes the Proliferation and Metastasis of Human Lung Tumor Cells by Regulating MicroRNA-144

Dagang Li,* Huizong Li,† Yuping Yang,* and Le Kang*

*Department of Respiratory Medicine, East Medical District of Linyi People’s Hospital, Linyi, Shandong, P.R. China
†Internal Medicine Ward III, Mengyin Hospital of Traditional Chinese Medicine, Mengyin, Shandong, P.R. China

Long noncoding RNA urothelial carcinoma-associated 1 (lncRNA UCA1) has gained more attention in recent years due to its oncogenic roles in various cancers. MicroRNA-144 (miR-144) participates in the regulation of the growth of many cancer cells. This study investigated the interaction between lncRNA UCA1 and miR-144 in lung cancer cells. The potential downstream protein of miR-144 was also assessed. Our results found that lncRNA UCA1 was highly expressed in human lung cancer A549, H517, H4006, H1299, and H1650 cells compared to normal embryonic lung WI-38 and HEL-1 cells. Knockdown of lncRNA UCA1 significantly inhibited lung cancer A549 cell viability, migration, invasion, and cell cycle progression, but promoted cell apoptosis. Besides, we found that lncRNA UCA1 was bound to miR-144. miR-144 participated in the regulation effects of lncRNA UCA1 on A549 cell viability, migration, invasion, cell cycle transition, and cell apoptosis. In addition, Pre-B-cell leukemia homeobox 3 (PBX3) was found to be a direct target gene of miR-144. Overexpression of PBX3 promoted A549 cell proliferation and metastasis. Suppression of PBX3 had an opposite effect.

Key words: Lung cancer; Long noncoding RNA urothelial carcinoma-associated 1 (lncRNA UCA1); MicroRNA-144 (miRNA-144); Pre-B-cell leukemia homeobox 3 (PBX3); Cell proliferation; Cell metastasis

Address correspondence to Le Kang, Department of Respiratory Medicine, East Medical District of Linyi People’s Hospital, No. 233 Fenghuang Street, Hedong District, Linyi, Shandong 276000, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 547-556, 2018
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DOI: https://doi.org/10.3727/096504017X
15016337254605
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


miR-449a Suppresses LDHA-Mediated Glycolysis to Enhance the Sensitivity of Non-Small Cell Lung Cancer Cells to Ionizing Radiation

Liang Li,*1 Huijuan Liu,*1 Lianjiang Du,† Pan Xi,* Qian Wang,* Yanqin Li,‡ and Di Liu§

*Department of Radiotherapy, Shaanxi Provincial Tumor Hospital, Xi’an, P.R. China
†Department of Oncology, Ankang City Central Hospital, Ankang, P.R. China
‡School of Public Health, Xi’an Jiaotong University Health Science Center, Xi’an, P.R. China
§Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China

MicroRNA dysregulation contributes to malignant progression, dissemination, and profound treatment resistance in multiple cancers. miR-449a is recognized as a tumor suppresser. However, the roles of miR-449a in lung cancer initiation and progression are largely unknown. Our study aims to investigate the roles and underlying mechanism of miR-449a in modulating sensitivity to ionizing radiation (IR) in non-small cell lung cancer (NSCLC). Lung cancer cells were transfected with miR-449a mimics or negative control and exposed to IR; the levels of target protein, glycolysis, cell viability, apoptosis, and DNA damage were examined. miR-449a was suppressed in lung cancer tissues and cancer cells (A549 and H1299). IR exposure significantly increased the expression of miR-449a in A549 cells at doses ranging from 4 to 8 Gy at 24 h, whereas no significant change in miR-449a was found in H1299 cells after IR. When A549 cells were exposed to IR at a dose of 8 Gy, the miR-449a level only had an acute increase within 12 h. miR-449a restoration dramatically suppressed IR-induced cell apoptosis and DNA damage in both A549 and H1299 cells. Bioinformatics analysis indicated that lactate dehydrogenase A (LDHA) was a potential target of miR-449a. miR-449a mimic transfection substantially suppressed the LDHA expression and production of lactate catalyzed by LDHA as well as glucose uptake. We confirmed that miR-449a could bind to the 3′-UTR of LDHA mRNA using luciferase reporter assay. LDHA siRNA-transfected cells showed enhanced cell apoptosis and DNA damage in response to IR exposure. miR-449a upregulation enhanced IR sensitivity of lung cancer cells by suppressing LDHA and the subsequent glycolysis.

Key words: Non-small cell lung cancer (NSCLC); Ionizing radiation (IR); miR-449a; Lactate dehydrogenase A (LDHA); Glycolysis

1These authors provided equal contribution to this work.
Address correspondence to Di Liu, Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, No. 157 West 5th Road, Xi’an, Shaanxi 710004, P.R. China. Tel: 86-29-87679513; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 557-563, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15000784459799
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


MicroRNA-374a Promotes Hepatocellular Carcinoma Cell Proliferation by Targeting Mitogen-Inducible Gene 6 (MIG-6)

Hui Li,*1 Huicheng Chen,†1 Haibin Wang,‡ Yilong Dong,† Min Yin,† Liang Zhang,§ and Jia Wei*

*Department of Liver and Infectious Diseases, Liver Disease Research Center, The Second People’s Hospital of Yunnan Province, Kunming, P.R. China
†School of Medicine, Yunnan University, Kunming, P.R. China
‡The Second Department of Liver Diseases, The Third People’s Hospital of Kunming City, Kunming, P.R. China
§Liver Disease Research Center, The Second People’s Hospital of Yunnan Province, Kunming, P.R. China

Hepatocellular carcinoma (HCC) is a disease with poor prognosis rates and ineffective therapeutic options. Previous studies have reported the involvement of mitogen-inducible gene 6 (MIG-6) as a negative regulator in tumor formation. MicroRNAs (miRNAs) play crucial roles in the development of different types of cancer. However, the underlying mechanisms of miRNAs in HCC are poorly understood. This study was aimed to investigate the role of miR-374a in HCC and its role in the regulation of expression of MIG-6. The results showed that MIG-6 overexpression significantly inhibited cell viability of HepG2 cells after 4 days posttransfection. Moreover, MIG-6 was a direct target of miR-374a, and the expression of MIG-6 was remarkably downregulated by the overexpression of miR-374a in HepG2 cells. Furthermore, we found that overexpression of miR-374a promoted cell viability; however, the protective effect was abolished by MIG-6 overexpression. In addition, overexpression of miR-374a activated the EGFR and AKT/ERK signaling pathways by regulation of MIG-6. Our findings suggest that miR-374a could promote cell viability by targeting MIG-6 and activating the EGFR and AKT/ERK signaling pathways. These data provide a promising therapeutic strategy for HCC treatment.

Key words: MicroRNA-374a; Mitogen-inducible gene 6 (MIG-6); Hepatocellular carcinoma (HCC); Cell viability; EGFR/AKT/ERK pathways

1These authors provided equal contribution to this work.
Address correspondence to Jia Wei, Department of Liver and Infectious Diseases, Liver Disease Research Center, The Second People’s Hospital of Yunnan Province, No. 176 Qingnian Road, Kunming 650021, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 565-572, 2018
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DOI: https://doi.org/10.3727/096504017X
15044461944385
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


Overexpression of Glypican 5 (GPC5) Inhibits Prostate Cancer Cell Proliferation and Invasion via Suppressing Sp1-Mediated EMT and Activation of Wnt/β-Catenin Signaling

Yu Sun,1 Kai Xu,1 Miao He, Guilian Fan, and Hongming Lu

Department of Pathology, General Hospital of Daqing Oil Field, Daqing, P.R. China

Glypican 5 (GPC5) belongs to the family of heparan sulfate proteoglycans (HSPGs). It was initially known as a regulator of growth factors and morphogens. Recently, there have been reports on its correlation with the tumorigenic process in the development of some cancers. However, little is known about its precise role in prostate cancer (PCa). In the present study, we explored the expression pattern and biological functions of GPC5 in PCa cells. Our results showed that GPC5 was lowly expressed in PCa cell lines. Upregulation of GPC5 significantly inhibited PCa cell proliferation and invasion in vitro as well as attenuated tumor growth in vivo. We also found that overexpression of GPC5 inhibited the epithelial–mesenchymal transition (EMT) and Wnt/β-catenin signaling activation, which was mediated by Sp1. Taken together, we suggest GPC5 as a tumor suppressor in PCa and provide promising therapeutic strategies for PCa.

Key words: Glypican 5 (GPC5); Prostate cancer (PCa); Proliferation; Invasion; Epithelial–mesenchymal transition (EMT)

1These authors provided equal contribution to this work.
Address correspondence to Yu Sun, Department of Pathology, General Hospital of Daqing Oil Field, No. 9 Middle Kang Street, Saertu District, Daqing 163001, Heilongjiang Province, P.R. China. Tel: +86-0459-5886408; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 573-579, 2018
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DOI: https://doi.org/10.3727/096504017X
14954923820137
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


Downregulation of SRC Kinase Signaling Inhibitor 1 (SRCIN1) Expression by MicroRNA-32 Promotes Proliferation and Epithelial–Mesenchymal Transition in Human Liver Cancer Cells

Ren Chen,1 Jin-Yao Liao,1 Jing Huang,1 Wen-Li Chen, Xiao-Jun Ma, and Xiao-Dan Luo

Department of Infectious Diseases, Guangdong Academy of Medical Sciences, Guangdong General Hospital, Guangzhou, P.R. China

MicroRNAs play an important role in regulating gene expression by binding to the 3¢-UTR of target mRNAs. In this study, we have made an attempt to assess the molecular mechanisms by which miR-32 suppresses the expression of SRCIN1, thereby leading to promotion of proliferation and epithelial–mesenchymal transition of human liver cancer cells. Human liver cancer cell line HepG2 was transfected with miR-32 mimics and its control. The HepG2 cells were assessed for miR-32 expression. The transfected cells were then studied for SRCIN1 expression by luciferase assay, effect of transfection on cell proliferation, and epithelial–mesenchymal transition. SRCIN1 expression was downregulated in the human liver cancer cell line HepG2. Overexpression of SRCIN1 inhibited the proliferation of human liver HepG2 cancer cells and blocked epithelial–mesenchymal transition. It was observed that SRCIN1 expression was regulated by miR-32 in human liver cancer cells. Overexpression of miR-32 promoted cell proliferation and epithelial–mesenchymal transition of human liver cancer HepG2 cells. Our data demonstrated that SRCIN1 functions as a tumor suppressor in human liver cancers. Additionally, SRCIN1 functions to inhibit the proliferation and epithelial–mesenchymal transition of human liver cancer HepG2 cells. miRNA-32 was a direct target of SRCIN1. Overexpression of miR-32 promoted cell proliferation and epithelial–mesenchymal transition of human liver cancer HepG2 cells.

Key words: SRC kinase signaling inhibitor 1 (SRCIN1); miR-32; Epithelial–mesenchymal transition (EMT); Hepatocellular carcinoma (HCC)

1These authors provided equal contribution to this work.
Address correspondence to Ren Chen, Department of Infectious Diseases, Guangdong Academy of Medical Sciences, Guangdong General Hospital, No. 106 Zhongshan 2nd Road, Guangzhou 510080, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 581-591, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14953948675403
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


Knockdown of Long Noncoding RNA (lncRNA) Metastasis-Associated Lung Adenocarcinoma Transcript 1 (MALAT1) Inhibits Proliferation, Migration, and Invasion and Promotes Apoptosis by Targeting miR-124 in Retinoblastoma

Shujun Liu,*1 Guigang Yan,*1 Junfu Zhang,† and Lianzhi Yu‡

*Department of Ophthalmology, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, Shandong, P.R. China
†Department of Ophthalmology, Weifang People’s Hospital, Weifang, Shandong, P.R. China
‡Department of Physical Examination, Yantai Yuhuangding Hospital Affiliated to Qingdao University, Yantai, Shandong, P.R. China

Evidence suggests that the long noncoding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is upregulated in cancer tissues, and its elevated expression is associated with hyperproliferation. However, the underlying mechanisms regarding the role of MALAT1 in retinoblastoma (RB) remain unclear. This study aimed to explore the functional role of MALAT1 in RB by targeting miR-124. The results showed that the expression of MALAT1 was significantly higher in the Y79 cell line than in the ARPE-19 cell line (p < 0.01). Moreover, MALAT1 silence inhibited cell viability, migration, and invasion and promoted apoptosis in Y79 cells (p < 0.05, p < 0.01, or p < 0.001). miR-124 was upregulated by MALAT1 silence and hence was identified as a target of MALAT1 (p < 0.05 or p < 0.001). In addition, miR-124 suppression inhibited cell apoptosis and remarkably abolished the inhibitory effects of MALAT1 silence on cell viability, migration, and invasion (p < 0.05, p < 0.01, or p < 0.001). In addition, Slug was a target of miR-124 and regulated cell viability, migration, invasion, and apoptosis in Y79 cells (p < 0.05, p < 0.01, or p < 0.001). Further, Slug silence abolished miR-124 suppression-induced inactivation of the ERK/MAPK and Wnt/β-catenin pathways. Taken together, our data highlight the pivotal role of MALAT1 in RB. Moreover, the present study elucidated the MALAT1–miR-124–ERK/MAPK and Wnt/b-catenin signaling pathways in RB, which might provide a new approach for the treatment of RB.

Key words: Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1); Retinoblastoma (RB); miR-124; ERK/MAPK pathway; Wnt/b-catenin pathway

1These authors are co-first authors.
Address correspondence to Junfu Zhang, Department of Ophthalmology, Weifang People’s Hospital, No. 151 Guangwen Street, Kuiwen District, Weifang 261041, Shandong, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 593-604, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14920318811712
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


MicroRNA-520b Functions as a Tumor Suppressor in Colorectal Cancer by Inhibiting Defective in Cullin Neddylation 1 Domain Containing 1 (DCUN1D1)

Jing Xiao,* Guang Li,† Jingyu Zhou,‡ Shalong Wang,‡ Dongcai Liu,‡ Guoshun Shu,‡ Jianping Zhou,‡ and Feng Ren‡

*Minimally Invasive Surgery Center, The Second Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China
†Department of Gastrointestinal Surgery, People’s Hospital of Linyi City, Linyi, Shandong, P.R. China
‡Department of Gerontological Surgery, The Second Xiangya Hospital of Central South University, Changsha, Hunan, P.R. China

MicroRNAs (miRs), a class of small noncoding RNAs, are important regulators for gene expression through directly binding to the 3′-untranslated region (3′-UTR) of their target mRNA. Recently, downregulation of miR-520b has been observed in several common human cancers. However, the exact role of miR-520b in colorectal cancer (CRC) has not previously been studied. In this study, our data showed that miR-520b was significantly downregulated in CRC and cell lines when compared with adjacent normal tissues and a normal intestinal epithelial cell line. Low expression of miR-520b was notably associated with the malignant progress and a shorter survival time for CRC patients. Restoration of miR-520b inhibited cell proliferation, migration, invasion, and epithelial–mesenchymal transition (EMT) in CRC cells. Defective in cullin neddylation 1 domain containing 1 (DCUN1D1) was then identified as a novel target gene of miR-520b in CRC cells. The expression of DCUN1D1 was significantly increased in CRC, with a negative correlation to miR-520b expression in CRC tissues. Moreover, a high expression of DCUN1D1 was significantly associated with the malignant progress and a poor prognosis for CRC patients. Furthermore, overexpression of DCUN1D1 rescued the miR-520b-mediated malignant phenotypes and EMT in CRC cells. The data demonstrate that miR-520b functions as a tumor suppressor in CRC through targeting DCUN1D1, suggesting that miR-520b may become a potential therapeutic target for the treatment of CRC.

Key words: Colorectal cancer (CRC); MicroRNA; Epithelial–mesenchymal transition (EMT); Defective in cullin neddylation 1 domain containing 1 (DCUN1D1); Tumor suppressor

Address corresponding to Professor Feng Ren, Department of Gerontological Surgery, The Second Xiangya Hospital of Central South University, 139 Renmin Road, Changsha, Hunan 410001, P.R. China. Tel: +86-731-85295888; Fax: +86-731-85295888; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 605-616, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15009778205068
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


Activation of Vimentin Is Critical to Promote a Metastatic Potential of Cholangiocarcinoma Cells

Waraporn Saentaweesuk,*†‡ Norie Araki,‡ Kulthida Vaeteewoottacharn,*† Atit Silsirivanit,*†‡ Wunchana Seubwai,†§ Chutima Talabnin,¶ Kanha Muisuk,§ Banchob Sripa,†# Sopit Wongkham,*† Seiji Okada,** and Chaisiri Wongkham*†

*Department of Biochemistry, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
†Cholangiocarcinoma Research Institute, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
‡Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, Kumamoto, Japan
§Department of Forensic Medicine, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
¶School of Biochemistry, Institute of Science, Suranaree University of Technology, Nakhon Ratchasima, Thailand
#Department of Pathology, Faculty of Medicine, Khon Kaen University, Khon Kaen, Thailand
**Division of Hematopoiesis, Center of AIDS Research, Kumamoto University, Kumamoto, Japan

Cholangiocarcinoma (CCA) is a highly metastatic tumor, and the majority of patients with CCA have a short survival time because there are no available effective treatments. Hence, a better understanding regarding CCA metastasis may provide an opportunity to improve the strategies for treatment. A comparison study between the highly metastatic cells and their parental cells is an approach to uncover the molecular mechanisms underlying the metastatic process. In the present study, a lung metastatic CCA cell line, KKU-214L5, was established by the in vivo selection of the tail vein-injected mouse model. KKU-214L5 cells possessed mesenchymal spindle-like morphology with higher migration and invasion abilities in vitro than the parental cells (KKU-214). KKU-214L5 also exhibited extremely aggressive lung colonization in the tail vein-injected metastatic model. Epithelial–mesenchymal transition (EMT) was clearly observed in KKU-214L5 cells. Significant downregulation of epithelial markers (ZO-1 and claudin-1), with unique upregulation of E-cadherin and mesenchymal markers (vimentin, β-catenin, and slug), was observed in KKU-214L5. Increasing MMP-2 and MMP-9 activities and CD147 expression reflected the high invasion activity in KKU-214L5 cells. Suppression of vimentin using siRNA significantly decreased the migration and invasion capabilities of KKU-214L5 to almost the basal levels of the parental cells without any change on the expression levels of other EMT markers and the activities of MMPs. These results suggest that vimentin activation is essential to potentiate the metastatic characters of CCA cells, and suppression of vimentin expression could be a potential strategy to improve the treatment of CCA, a highly metastatic cancer.

Key words: Bile duct cancer; Epithelial–mesenchymal transition (EMT); Metastasis; Metalloproteinases (MMPs)

Address correspondence to Associate Professor Chaisiri Wongkham, Department of Biochemistry, Faculty of Medicine, Khon Kaen University, 123 Mitraparb Road, MuangKhon Kaen 40002, Thailand. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Associate Professor NorieAraki, Department of Tumor Genetics and Biology, Graduate School of Medical Sciences, Kumamoto University, 1-1-1 Honjo, Kumamoto 860-8556, Japan. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 617-624, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15043589260618
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Knockdown of Gab1 Inhibits Cellular Proliferation, Migration, and Invasion in Human Oral Squamous Carcinoma Cells

Luyong Xu, Jie Li, Zheng Kuang, Yan Kuang, and Hong Wu

Department of Stomatology, Rizhao People’s Hospital, Jining Medical University, Rizhao, P.R. China

Grb2-associated binder 1 (Gab1) is often aberrant in cancerous cells and tissues, whose alteration is responsible for aggressive phenotypes. In this study, we examined the Gab1 expression in human oral squamous cell carcinoma (OSCC) tissues and investigated the cellular and molecular effect of Gab1 on migration, invasion, and cell growth of the OSCC cell lines SCC15 and SCC25. We found that Gab1 was overexpressed in OSCC tissues and cells, which is related to the protein levels of various molecules associated with cellular proliferation, migration, and invasion. Functional assays identified that Gab1 overexpression promoted cell proliferation and invasion of OSCC cells and inhibited cell apoptosis in the SCC15 and SCC25 cell lines. On the other hand, Gab1 silencing affected the proliferation and invasion of OSCC cells and induced cell apoptosis. Western blot assay identified that Gab1 overexpression suppressed the expression of Cdc20 homolog 1 (Cdh1) and then promoted cell invasion in OSCC cells. Furthermore, Gab1-mediated Cdh1 downregulation was significantly reversed when the cells were subjected to an inhibitor of p-Akt. In conclusion, these results suggested that Gab1 induced malignant progression of OSCC cells probably via activation of the Akt/Cdh1 signaling pathway. Thus, Gab1 may be a potential therapeutic target in the treatment of OSCC patients.

Key words: Grb2-associated binder 1 (Gab1); Cdc20 homolog 1 (Cdh1); Malignance; Oral squamous cell carcinoma (OSCC)

Address correspondence to Luyong Xu, Department of Stomatology, Rizhao People’s Hospital, Jining Medical University, Taian Road 126, Rizhao 276826, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 625-635, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14953948675395
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Long Noncoding RNA CAMTA1 Promotes Proliferation and Mobility of the Human Breast Cancer Cell Line MDA-MB-231 via Targeting miR-20b

Pengwei Lu, Yuanting Gu, Lin Li, Fang Wang, Xue Yang, and Yunqing Yang

Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China

Breast cancer is a serious threat to women’s physical and psychological health. Long noncoding RNA CAMTA1 (lncCAMTA1) was believed to be related with tumor progression, but its role in breast cancer is not clear. The human breast cancer cell line MDA-MB-231 was used to investigate the effect of lncCAMTA1 on cell viability, migration/invasion, and apoptosis. The expression of lncCAMTA1, miR-20b, and VEGF in MDAMB-231 were measured after corresponding transfections. Binding effects between lncCAMTA1 and miR-20b, miR-20b, and VEGF 3′-UTR were measured. The effects of miR-20b and VEGF on breast cancer cells were also assessed after transfections. The phosphorylation levels of the MAPK/ERK and JAK/STAT3 pathways were determined to assess the effect of VEGF. The results showed that lncCAMTA1 expression promoted cell viability and migration/invasion, while knockdown of lncCAMTA1 promoted cell apoptosis via binding with miR-20b. lncCAMTA1 negatively regulated miR-20b expression. VEGF was a target of miR-20b, leading to the modification of the phosphorylation levels of MAPK, ERK, JAK, STAT1, and STAT3. Our findings suggested that lncCAMTA1 might promote proliferation and mobility of human breast cancer cells via binding with miR-20b. VEGF was a direct target of miR-20b and regulated activation of the MAPK/ERK and JAK/STAT3 signaling pathways. Therefore lncCAMTA1 has potential as a novel cancer diagnostic marker and as a putative novel therapeutic target for breast cancer treatment.

Key words: Long noncoding RNA CAMTA1 (lncCAMTA1); MicroRNA-20b (miR-20b); Vascular endothelial growth factor (VEGF); Janus kinase/stat (JAK/STAT) signaling pathway; Mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK)

Address correspondence to Yuanting Gu, Department of Breast Surgery, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Zhengzhou 450052, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 637-644, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15112639918174
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


miR-767-3p Inhibits Growth and Migration of Lung Adenocarcinoma Cells by Regulating CLDN18

Yi Long Wan,* Han Jue Dai,† Wei Liu,‡ and Hai Tao Ma*

*Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China
†Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China
‡Department of Cardiology, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu, P.R. China

Claudin18 (CLDN18) is necessary for intercellular junctions and is reported to be involved in cell migration and metastasis, making it like an oncogene in various cancer types. However, the biological function and regulatory mechanisms of CLDN18 in lung adenocarcinoma are not yet clear. In this study, we found downregulation of miR-767-3p and upregulation of CLDN18 in lung adenocarcinoma tissue and cell lines. In addition, there was a negative correlation between the expression of miR-767-3p and CLDN18 in lung adenocarcinoma. Double luciferase reporter gene analysis showed that miR-767-3p modulates the expression of CLDN18 by binding its 3′-untranslated regions (3′-UTR). Knockdown of CLDN18 results in a decrease in the growth, migration, and invasion of lung adenocarcinoma cells. Although overexpression of miR-767-3p inhibits lung adenocarcinoma cell growth and migration, these effects can be rescued by reexpressing CLDN18. In summary, the data suggest that miR-767-3p inhibits tumor cell proliferation, migration, and invasion by targeting CLDN18, providing a promising therapeutic target for lung adenocarcinoma.

Key words: miR-767-3p; Lung adenocarcinoma; Claudin 18 (CLDN18); Migration; Invasion

Address correspondence to Dr. Hai Tao Ma, Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, 188 Shizi Street, Suzhou, Jiangsu 215006, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 645-653, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15031557924141
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


Baicalein Inhibits the Proliferation of Cervical Cancer Cells Through the GSK3β-Dependent Pathway

Xiaoling Wu,*1 Zhiqin Yang,†1 Huimin Dang,‡ Huixia Peng,* and Zhijun Dai§

*Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China
†Department of Traditional Chinese Medicine, Yan’an People’s Hospital, Yan’an, P.R. China
‡Department of Integrated Traditional Chinese and Western Medicine, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China
§Department of Oncology, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, P.R. China

Baicalein, a flavonoid derived from the root of Scutellaria baicalensis, has been reported to possess multiple pharmacological activities, such as anticancer and anti-inflammatory properties. This study investigated the effect of baicalein in cervical cancer cells. Cell growth curve and MTT assay were performed and revealed that baicalein inhibited the proliferation of SiHa and HeLa cells in a dose-dependent manner. We further found that baicalein arrested the cell cycle of SiHaand HeLa cells at the G0/G1
phase by suppressing the expression of cyclin D1 through the downregulation of phosphorylated protein kinase B (p-AKT) and phosphorylated glycogen synthase kinase 3β (p-GSK3β) according to FACS assays and Western blotting. Moreover, when CHIR-99021, a GSK3β inhibitor, was added to baicalein-treated SiHa cells, the expression of cyclin D1 was recovered, and cell proliferation was promoted. In conclusion, these data indicated that baicaleinsuspended the cell cycle at the G0/G1 phase via the downregulation of cyclin D1 through the AKT–GSK3β signaling pathway and further inhibited the proliferation of SiHa and HeLa cervical cancer cells.

Key words: Baicalein; Cyclin D1; Glycogen synthase kinase 3β (GSK3β); Cervical cancer; Proliferation

1These authors provided equal contribution to this work.
Address correspondence to Huixia Peng, Department of Obstetrics and Gynecology, The Second Affiliated Hospital of Xi’an Jiaotong University, 157 Xiwu Road, Xi’an, Shaanxi 710004, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 655-664, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15119525209765
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.


Proteasome Inhibitor MG132 Enhances Cisplatin-Induced Apoptosis in Osteosarcoma Cells and Inhibits Tumor Growth

Farui Sun,* Yuanjin Zhang,* Lijun Xu,* Songbai Li,* Xiang Chen,* Ling Zhang,* Yifan Wu,† and Jun Li*

*Department of Orthopedics, Huangshi Central Hospital, Affiliated Hospital of Hubei Polytechnic University, Edong Healthcare Group, Huangshi, Hubei, P.R. China
†International Education College, Hebei Finance University, Baoding, Hebei, P.R. China

Although cisplatin has been shown to be an integral part of chemotherapy regimen in osteosarcoma (OS) treatment, toxicity issues and chemoresistance have hindered therapeutic development for OS. Exploring novel combination therapy methods is needed to circumvent the limitations of cisplatin alone. The proteasome inhibitor MG132 has shown antitumor effects in many solid tumors. However, little is known about its effects in combination with cisplatin in OS cells. In this study, we examined the effects of MG132 in combination with cisplatin in human OS cells (MG-63 and HOS). MG132 and cisplatin were applied to OS cells, respectively or jointly. The results demonstrated that MG132 markedly inhibited cell viability in a dose- and time-dependent manner, whereas viability of osteoblast cells was not affected, suggesting a selective toxicity of MG132 to cancerous cells. Mechanistically, MG132 arrested cells in the G2/M phase in association with increased p21waf1
and induced cell apoptosis, which was accompanied by cleaved PARP. In addition to its apoptotic effect alone, MG132 significantly enhanced cisplatin-induced apoptosis in OS cells. Furthermore, cell viability of the combined application of 10 μM MG132 and 5 μg/ml cisplatin was markedly inhibited compared to that of the individual application. These events were accompanied by the downregulation of NF-κB, mitochondrial antiapoptotic protein Bcl-xL, and PI3K/Akt, which play a key role in cell survival. Finally, combination treatment of MG132 and cisplatin showed more antiproliferative effect than the single treatment in OS xenograft models. In summary, we concluded that MG132 interacted synergistically with cisplatin, which raised the possibility that combining the two drugs may represent a novel strategy in OS.

Key words: MG132; Osteosarcoma (OS); Cisplatin; Synergistic efficacy; Cell viability; Apoptosis

Address correspondence to Jun Li, Department of Orthopedics, Huangshi Central Hospital, Hubei Polytechnic University, 141 Tianjin Road, Huangshi, 435000 Hubei Province, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it