Oncology Research 25(3) Abstracts

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Oncology Research, Vol. 25, pp. 305-316, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14734149559061
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

ABCB5–ZEB1 Axis Promotes Invasion and Metastasis in Breast Cancer Cells

Juntao Yao,*† Xuan Yao,‡ Tao Tian,* Xiao Fu,* Wenjuan Wang,* Suoni Li,§ Tingting Shi,* Aili Suo,* Zhiping Ruan,* Hui Guo,* Kejun Nan,* and Xiongwei Huo

*Department of Oncology, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China
†The Integrated Department of TCM and Western Medicine, Shaanxi Provincial Tumor Hospital, Xi’an, Shaanxi, P.R. China
‡Department of Thoracic Surgery, The Center Hospital of Xi’an, Shaanxi, P.R. China
§Department of Oncology, Shaanxi Provincial Tumor Hospital, Xi’an, Shaanxi, P.R. China
¶Department of General Surgery, First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China

ABCB5 belongs to the ATP-binding cassette (ABC) superfamily, which is recognized for playing a role in the failure of chemotherapy. ABCB5 has also been found to be overexpressed at the transcriptional level in a number of cancer subtypes, including breast cancer. However, the exact mechanism ABCB5 uses on cancer cell metastasis is still unclear. In the present study, we demonstrate that ABCB5 expression was increased in metastatic tissues when compared with nonmetastatic tissues. ABCB5 can significantly enhance metastasis and epithelial–mesenchymal transition (EMT), while knockdown of ABCB5 inhibited these processes. Microarray analysis indicated that ZEB1 may function as a downstream factor of ABCB5. Furthermore, the expression of ZEB1 in tissues is positively relevant to ABCB5 in breast cancer. Knocking down ZEB1 inhibits ABCB5 ectopic expression-induced migration and invasion, as well as EMT. Taken together, these results helped to realize the oncogene functions of ABCB5 in breast cancer cells and provided a new direction in treating breast cancer.

Key words: ABCB5; Breast cancer; Epithelial–mesenchymal transition (EMT); ZEB1

Address correspondence to Kejun Nan, Department of Oncology, First Affiliated Hospital of Xi’an Jiaotong University, No. 28 Xianning West Road, Xi’an, Shaanxi 710049, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Xiongwei Huo, Department of General Surgery, First Affiliated Hospital of Xi’an Jiaotong University, No. 28 Xianning West Road, Xi’an, Shaanxi 710049, 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. 317-329, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14734735156265
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Silencing of ATP4B of ATPase H+/K+ Transporting Beta Subunit by Intragenic Epigenetic Alteration in Human Gastric Cancer Cells

Shuye Lin,*† Bonan Lin,* Xiaoyue Wang,* Yuanming Pan,‡ Qing Xu,* Jin-Shen He,* Wanghua Gong,§ Rui Xing,‡ Yuqi He,¶ Lihua Guo,* Youyong Lu,‡ Ji Ming Wang,† and Jiaqiang Huang*†

*College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, Beijing, P.R. China
†Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, Frederick, MD, USA
‡Laboratory of Molecular Oncology, Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education), Peking University Cancer Hospital/Institute, Beijing, P.R. China
§Basic Research Program, Leidos Biomedical Research, Inc., Frederick, MD, USA
¶Department of Gastroenterology, PLA Army General Hospital, Beijing, P.R. China

The ATPase H+/K+ Transporting Beta Subunit (ATP4B) encodes the β subunit of the gastric H+, K+-ATPase, which controls gastric acid secretion and is therefore a target for acid reduction. Downregulation of ATP4B was recently observed in human gastric cancer (GC) without known mechanisms. In the present study, we demonstrated that ATP4B expression was decreased in human GC tissues and cell lines associated with DNAhypermethylation and histone hypoacetylation of histone H3 lysine 9 at its intragenic region close to the transcriptional start site. The expression of ATP4B was restored in GC cell lines by treatment with the DNA methyltransferase inhibitor, 5-aza-2ʹ-deoxycytidine (5-AZA), or histone deacetylase inhibitor, trichostatin A (TSA), with further enhancement by combined treatment with both drugs. In contrast, 5-AZA had no effect on ATP4B expression in human hepatocellular carcinoma (HCC) and pancreatic cancer cell lines, in which ATP4B was silenced and accompanied by intragenic methylation. Chromatin immunoprecipitation (ChIP) showed that, in BGC823 GC cells, histone H3 lysine 9 acetylation (H3K9ac) was enhanced in the intragenic region of ATP4B upon TSA treatment, whereas 5-AZA showed a minimal effect. Additionally, ATP4B expression enhanced the inhibitory effects of chemotherapeutic mediation docetaxel on GC cell growth. Thus, as opposed to HCC and pancreatic cancer cells, the silencing of ATP4B in GC cells is attributable to the interplay between intragenic DNA methylation and histone acetylation of ATP4B, the restoration of which is associated with a favorable anticancer effect of docetaxel. These results have implications for targeting epigenetic alteration at the intragenic region of ATP4B in GC cells to benefit diagnosis and treatment of GC.

Key words: ATP4B; Gastric cancer (GC); Intragenic DNA methylation; Histone modification; Biomarker

Address correspondence to Dr. Jiaqiang Huang, College of Life Sciences and Bioengineering, School of Science, Beijing Jiaotong University, 3 Shangyuan CunHaidian District, Beijing 100044, P.R. China. Tel: +86-10-51684348; Fax: +86-10-51683887; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 331-340, 2017
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DOI: https://doi.org/10.3727/096504016X
14736286083065
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Knockdown of Ras-Related Protein 25 (Rab25) Inhibits the In Vitro Cytotoxicity and In Vivo Antitumor Activity of Human Glioblastoma Multiforme Cells

Bingqian Ding,1 Bei Cui,1 Ming Gao, Zhenjiang Li, Chenyang Xu, Shaokang Fan, and Weiya He

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

Ras-related protein 25 (Rab25) is a member of the Rab family, and it has been reported to play an important role in tumorigenesis. However, its direct involvement in human glioblastoma multiforme (GBM) is still unclear. The aim of the current study was to investigate the potential role of Rab25 in the growth, proliferation, invasion, and migration of human GBM. Our results showed that Rab25 expression was significantly higher in human GBM cell lines compared with a normal astrocyte cell line. In vitro functional studies revealed that knockdown of Rab25 reduced cell proliferation and inhibited invasion and migration of GBM cells. In vivo experiments showed that knockdown of Rab25 attenuated the tumor growth in nude mice. Finally, knockdown of Rab25 significantly inhibited the phosphorylation levels of PI3K and AKT in GBM cells. Taken together, these findings indicate that Rab25 may act as a tumor promoter in human GBM and that approaches to target Rab25 may provide a novel strategy to treat this disease.

Key words: Ras-related protein 25 (Rab25); Glioblastoma multiforme (GBM); Migration; Invasion

1These authors provided equal contribution to this work.
Address correspondence to Weiya He, Department of Neurology, Huaihe Hospital of Henan University, Baobei Road No. 8, Kaifeng 475000, P.R. China. Tel: +86-0371-23906530; Fax: +86-0371-23906058; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 341-353, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14737243054982
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Isolation and Characterization of Fast-Migrating Human Glioma Cells in the Progression of Malignant Gliomas

Vivian Adamski,* Anne Dorothée Schmitt,* Charlotte Flüh,* Michael Synowitz,* Kirsten Hattermann,†1 and Janka Held-Feindt*1

*Department of Neurosurgery, University Medical Center, Schleswig-Holstein UKSH, Campus Kiel, Kiel, Germany
†Department of Anatomy, University of Kiel, Kiel, Germany

Gliomas are the most common primary brain tumors. The most malignant form, the glioblastoma multiforme (GBM; WHO IV), is characterized by an invasive phenotype, which enables the tumor cells to infiltrate into adjacent brain tissue. When investigating GBM migration and invasion properties in vitro, in most cases GBM cell lines were analyzed. Comprehensive investigations focusing on progression-dependent characteristics of migration processes using fresh human glioma samples of different malignancy grades do not exist. Thus, we isolated fast-migrating tumor cells from fresh human glioma samples of different malignancy grades (astrocytomas WHO grade II, grade III, GBM, and GBM recurrences) and characterized them with regard to the transcription of genes involved in the migration and invasion, tumor progression, epithelial-to-mesenchymal transition, and stemness. In addition, we transferred our results to GBM cell lines and glioma stem-like cells and examined the influence of temozolomide on the expression of the above-mentioned genes in relation to migratory potential. Our results indicate that “evolutionary-like” expression alterations occur during glioma progression when comparing slow- and fast-migrating cells of fresh human gliomas. Furthermore, a close relation between migratory and stemness properties seems to be most likely. Variations in gene expression were also identified in GBM cell lines, not only when comparing fast- and slow-migrating cells but also regarding temozolomide-treated and untreated cells. Moreover, these differences coincided with the expression of stem cell markers and their migratory potential. Expression of migration-related genes in fast-migrating glioma cells is not only regulated in a progression-dependent manner, but these cells are also characterized by specific stem cell-like features.

Key words: Migration; Invasion; Epithelial-to-mesenchymal transition (EMT); Stemness; Gliomas; Progression

1These authors provided equal contribution to this work.
Address correspondence to Prof. Dr. Janka Held-Feindt, Ph.D., M.D., Department of Neurosurgery, University Medical Center, Schleswig-Holstein UKSH, Campus Kiel, Arnold-Heller-Str.3, Building 41, 24105 Kiel, Germany. Tel: +49(0)431-500-23679; Fax: +49(0)431-500-23678; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 355-364, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14738114257367
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

miR-218 Inhibits Proliferation, Migration, and EMT of Gastric Cancer Cells by Targeting WASF3

Guojun Wang, Yang Fu, Guanghui Liu, Yanwei Ye, and Xiefu Zhang

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

MicroRNAs (miRNAs) play an important role in carcinogenesis. miR-218 is one of the most known miRNAs and has been demonstrated to inhibit progression in gastric cancer. However, the underlying molecular mechanism is not established. In this study, qRT-PCR and Western blot indicated that miR-218 was downregulated in gastric cancer cell lines SGC7901 and BGC823 compared to that in normal gastric epithelial cell line GES-1. MTT and wound scratch assays suggested that overexpression of miR-218 markedly suppressed cell proliferation, migration, and EMT of gastric cancer cells. Furthermore, we proved that WASF3 was a direct target of miR-218 by luciferase reporter assay, and restoration of WASF3 expression impairs miR-218-induced inhibition of proliferation, migration, and EMT in gastric cancer cells SGC7901. In summary, our results demonstrated that miR-218 functions as one of the tumor-suppressive miRNAs and inhibits gastric cancer tumorigenesis by targeting WASF3. miR-218 may serve as a potential therapeutic target for the treatment of gastric cancer.

Key words: miR-218; Proliferation; Migration; Epithelial–mesenchymal transition (EMT); WASF3; Gastric cancer (GC)

Address correspondence to Guojun Wang, Department of Gastrointestinal Surgery, The First Affiliated Hospital of Zhengzhou University, East Jianshe Road 1, Zhengzhou 450052, P.R. China. Tel: +86-0371-67967137; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 365-372, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14738135889976
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Reduced Expression of Jumonji AT-Rich Interactive Domain 2 (JARID2) in Glioma Inhibits Tumor Growth In Vitro and In Vivo

Zhenjiang Li,*1 Chenyang Xu,*1 Ming Gao,* Bingqian Ding,* Xinting Wei,† and Nan Ji‡

*Department of Neurology, Huaihe Hospital of Henan University, Kaifeng, P.R. China
†Department of Neurosurgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China
‡Department of Neurosurgery, Tiantan Hospital, Capital Medical University, Beijing, P.R. China

Jumonji AT-rich interactive domain 2 (JARID2) is a member of the Jumonji family of proteins and has been proposed as an oncogene in several types of human cancer. However, the role of JARID2 in human glioma has not yet been understood. The present study was designed to determine the roles of JARID2 in the proliferation and migration in human glioma cells and the growth of glioma cells in nude mice. Our data indicate that JARID2 is upregulated in human glioma tissues and cell lines. Knockdown of JARID2 obviously inhibits the proliferation of U87MG cells and tumor growth in vivo. Furthermore, knockdown of JARID2 inhibits migration and invasion as well as the epithelial–mesenchymal transition (EMT) process in U87MG cells. Mechanistically, knockdown of JARID2 reduces the phosphorylation levels of PI3K and Akt in U87MG cells. In summary, our study is the first one in our knowledge to indicate that JARID2 plays an important role in glioma development and progression. Therefore, JARID2 may serve as a potential therapeutic target for the treatment of glioma.

Key words: Jumonji AT-rich interactive domain 2 (JARID2); Glioma; Proliferation; Invasion

1These authors provided equal contribution to this work.
Address correspondence to Bingqian Ding, Department of Neurology, Huaihe Hospital of Henan University, Baobei Road No. 8, Kaifeng 475000, P.R. China. Tel: +86-0371-23906530; Fax: +86-0371-23906516; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  


Oncology Research, Vol. 25, pp. 373-380, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14741486659473
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Long Noncoding RNA CPS1-IT1 Suppresses Cell Proliferation and Metastasis in Human Lung Cancer

Zhao Xiaoguang,*1,2 Liu Meirong,†1 Zhang Jingjing,‡ Zhang Ruishen,§ Zhang Qing,¶ and Tan Xiaofeng†2

*Department of Neurosurgery, CPLA Bethune International Peace Hospital, Shijiazhuang, Hebei, P.R. China
†College of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei, P.R. China
‡Department of Chest Surgery, The Chest Hospital of Hebei Province, Shijiazhuang, Hebei, P.R. China
§Hospital of China Railway Electric Bureau Group, First Engineering Company, Shijiazhuang, Hebei, P.R. China
¶Department of Neurology, The Chest Hospital of Hebei Province, Shijiazhuang, Hebei, P.R. China

The long noncoding CPS1 intronic transcript 1 (lncRNA CPS1-IT1) is a recently identified tumor suppressor in the lncRNA family of proteins. Whether this lncRNA plays any functional role in solid tumors remains largely unknown. The present study aimed to investigate the role of lncRNA CPS1-IT1 in human lung cancer. Expression of lncRNA CPS1-IT1 was initially assessed in human lung cancer and in a series of lung cancer cell lines. The effects of CPS1-IT1 overexpression on cell proliferation, migration, and invasion were examined in lung cancer cell lines A549 and 95D. It was found that lncRNA CPS1-IT1 was significantly lower in cancerous tissues than in noncancerous tissues. lncRNA CPS1-IT1 was differentially expressed in lung cancer cell lines and expressed the least in two highly invasive cell lines, A549 and 95D. Overexpression of CPS1-IT1 slowed down cell proliferation by 35.7% in A549 cells and 30.8% in 95D cells on the fifth day. Cell migration was inhibited by 59% in A549 cells and 48% in 95D cells, and cell invasion was suppressed by 60% in both cell lines after overexpression of CPS1-IT1. While cell apoptosis was induced, CPS1-IT1 overexpression promoted the activities of caspase 3 and caspase 9 without affecting that of caspase 8. These observations were suggestive of the tumor-suppressive role of lncRNA CPS1-IT1 in lung cancer. Our data suggest that CPS1-IT1 may be used as a biomarker for early diagnosis and therapeutic targets against lncRNA and may be promising in the treatment of lung cancer.

Key words: Long noncoding RNA (lncRNA); CPS1-IT1; Lung cancer; Proliferation; Metastasis

1These authors provided equal contribution to this work as co-first authors.
2These authors provided equal contribution to this work as co-corresponding authors.
Address correspondence to Xiaofeng Tan, Department of General Internal Medicine, Tianjin Hospital, No. 406 Jiefang South Road, Tianjin 300211, P.R. China. Tel: +86-022-28332713; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Xiaoguang Zhao, Department of Neurosurgery, CPLA Bethune International Peace Hospital, Shijiazhuang, Hebei, P.R. China. Tel: +86-0311-87998224; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 381-388, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14741511303522
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Knockdown of Tripartite-59 (TRIM59) Inhibits Cellular Proliferation and Migration in Human Cervical Cancer Cells

Gulijiahan Aierken,1 Ayinuer Seyiti,1 Mayinuer Alifu, and Gulina Kuerban

Department of Gynecology, The Affiliated Tumor Hospital of Xinjiang Medical University, Urumqi, Xinjiang, P.R. China

The tripartite motif (TRIM) family of proteins is a class of highly conservative proteins that have been implicated in multiple processes. TRIM59, one member of the TRIM family, has now received recognition as a key regulator in the development and progression of human diseases. However, its role in human tumorigenesis has remained largely unknown. In this study, the effects of TRIM59 expression on cell proliferation and migration were investigated in human cervical cancer cells. The expression of TRIM59 in clinical cervical cancer tissues and cervical cancer cells was initially determined by RT-PCR and Western blot. Specific shRNA against TRIM59 was then employed to knock down the expression of TRIM59 in cervical cancer lines HeLa and SiHa. The effects of TRIM59 knockdown on cell proliferation was assessed by MTT assay and colony formation assay. Transwell assay was conducted to reveal cell migration and invasion abilities before and after TRIM59 knockdown. Our results showed that the expression of TRIM59 was significantly elevated in cervical cancers. Knockdown of TRIM59 significantly inhibited cell proliferation and colony formation as well as cell migration and invasion abilities in cervical cancer HeLa and SiHa cells. Cell cycle progression analysis showed that TRIM59-depleted cells preferred to accumulate in the S phase. These data suggest that TRIM59 is a potential target that promotes the progression of cervical cancer.

Key words: TRIM59; Proliferation; Migration; Invasion; Cervical cancer

1These authors provided equal contribution to this work.
Address correspondence to Gulina Kuerban, M.D., Department of Gynaecology, The Affiliated Tumor Hospital of Xinjiang Medical University, 789 Suzhou Road, Urumqi 830011, Xinjiang, P.R. China. Tel: +86-0991-7968027; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 389-395, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14743324568129
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Knockdown of Serine–Arginine Protein Kinase 1 Inhibits the Growth and Migration in Renal Cell Carcinoma Cells

Xingtao Han,*† Jinjian Yang,* Zhankui Jia,* Pengtao Wei,† Han Zhang,† Wenwei Lv,† Jiantao Sun,† and Qingxiang Huo

*Department of Urology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China
†Department of Urology, Luoyang Central Hospital affiliated to Zhengzhou University, Luoyang, P.R. China

The pre-mRNA splicing regulator serine–arginine protein kinase 1 (SRPK1), a member of the SR kinase family, plays an essential role in cancer development and various pathophysiological processes. However, its expression pattern and functions in renal cell carcinoma (RCC) remain unknown. Therefore, the aim of this study was to assess the role of SRPK1 in RCC. Our data showed that SRPK1 was significantly upregulated in human RCC tissues and cell lines. SRPK1 interference significantly inhibited the proliferation of RCC cells and inhibited tumor growth in vivo. In addition, SRPK1 interference also suppressed migration and invasion in RCC cells. A mechanistic study showed that SRPK1 interference inhibited the phosphorylation of PI3K and Akt in RCC cells. In conclusion, our findings suggest that SRPK1 interference inhibits the growth and invasion of RCC cells through suppressing the PI3K/Akt signaling pathway. Thus, SRPK1 might be a therapeutic target for the treatment of RCC.

Key words: Serine–arginine protein kinase 1 (SRPK1); Renal cell carcinoma (RCC); Invasion; PI3K/Akt pathway

Address correspondence to Jinjian Yang, Department of Urology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe Road, Erqi District, Zhengzhou 450052, P.R. China. Tel: +86-0371-67967221; Fax: +86-0371-67967221; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 397-405, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14743337535446
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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MicroRNA-33b Inhibits the Proliferation and Migration of Osteosarcoma Cells via Targeting Hypoxia-Inducible Factor-1α

Yong Zhou, Chuandong Yang, Kunpeng Wang, Xuefeng Liu, and Quan Liu

Department of Second Orthopedics, Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, P.R. China

Recently, microRNA (miR)-33b has been demonstrated to act as a tumor suppressor in osteosarcoma. However, the regulatory mechanism of miR-33b in osteosarcoma cell proliferation and migration remains largely unknown. In this study, real-time PCR showed that miR-33b was significantly downregulated in osteosarcoma tissues compared to their matched adjacent nontumor tissues. Its expression was also decreased in several common osteosarcoma cell lines, including Saos-2, MG63, U2OS, and SW1353, when compared to normal osteoblast cell line hFOB. Overexpression of miR-33b suppressed U2OS cell proliferation and migration. HIF-1α was further identified as a target of miR-33b, and its protein levels were reduced after overexpression of miR-33b in U2OS cells. Moreover, overexpression of HIF-1α significantly reversed the suppressive effect of miR-33b on U2OS cell proliferation and migration. In addition, HIF-1α was found to be significantly upregulated in osteosarcoma tissues compared to adjacent nontumor tissues, and their expression levels were inversely correlated to the miR-33b levels in osteosarcoma tissues. According to these findings, miR-33b plays a suppressive role in the regulation of osteosarcoma cell proliferation and migration via directly targeting HIF-1α. Therefore, we suggest that the miR-33b/HIF-1α axis may become a promising therapeutic target for osteosarcoma.

Key words: Osteosarcoma; MicroRNA; Proliferation; Migration; Hypoxia-inducible factor-1α

Address correspondence to Professor Xuefeng Liu, Department of Second Orthopedics, Fourth Affiliated Hospital of Harbin Medical University, 37 Yiyuan Road, Harbin, Heilongjiang 150001, P.R. China. Tel/Fax: +86-541-85939210; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 407-415, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14743350548249
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
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Suppression of Asparaginyl Endopeptidase Inhibits Polyomavirus Middle T Antigen-Induced Tumor Formation and Metastasis

Cheng Xu,*1 Lu Cao,*1 Jianhua Liu,†1 Zhongrun Qian,‡ Yu Peng,§ Wenjing Zhu,§ Yongming Qiu,‡ and Yingying Lin‡¶

*Department of Radiation Oncology, Ruijin Hospital, Shanghai, P.R. China
†Institute of Medical Science, Shanghai Jiao Tong University School of Medicine, Shanghai, P.R. China
‡Department of Neurosurgery, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China
§Department of Urology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, P.R. China
¶Shanghai Institute of Head Trauma, Shanghai, P.R. China

Elevated circulating asparaginyl endopeptidase (AEP), a novel lysosomal protease, has been found in breast cancer, and AEP is thus considered to be a prognostic factor in this disease. However, the pathological functions of circulating AEP in the development of breast cancer and the potential of AEP-targeted therapy remain unclear. We used MMTV-PyVmT transgenic mice, which spontaneously develop mammary tumors. Western blotting showed overexpression of AEP in both primary tumor tissue and lung metastases compared to their normal counterparts. Moreover, the concentration of circulating AEP gradually increased in the serum during the development of mammary tumors. Purified AEP protein injected through the tail vein promoted tumor growth and mammary tumor metastasis and shortened survival, whereas AEP-specific small compound inhibitors (AEPIs) effectively suppressed tumor progression and prolonged host survival. Further analysis of the molecular mechanism revealed that AEP was important for PI3K/AKT pathway activation. Thus, an elevated serum AEP level was closely related to mammary cancer progression and metastasis, and AEP is a potential target for breast cancer therapy in the clinic.

Key words: Asparaginyl endopeptidase (AEP); Breast cancer; Transgenic mice; Metastasis

1These authors provided equal contribution to this work.
Address correspondence to Yingying Lin, Ph.D., Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Room 118, Building 11, 1630 Dongfang Road, Pudong District, Shanghai 200127, P.R. China. Tel: (86) 15800727180; Fax: (86) 021-58394262; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Yongming Qiu, M.D., Ph.D., Department of Neurosurgery, Ren Ji Hospital, Shanghai Jiao Tong University School of Medicine, Room 118, Building 11, 1630 Dongfang Road, Pudong District, Shanghai 200127, P.R. China. Tel: (86) 18221770005; Fax: (86) 021-58394262; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 417-425, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14747253292210
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Knockdown of DDX46 Inhibits the Invasion and Tumorigenesis in Osteosarcoma Cells

Feng Jiang,1 Dengfeng Zhang,1 Guojun Li, and Xiao Wang

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

DDX46, a member of the DEAD-box (DDX) helicase family, is involved in the development of several tumors. However, the exact role of DDX46 in osteosarcoma and the underlying mechanisms in tumorigenesis remain poorly understood. Thus, in the present study, we explored the role of DDX46 in osteosarcoma and the underlying mechanisms. Our results demonstrated that the expression levels of DDX46 in both mRNA and protein were greatly elevated in human osteosarcoma tissues and cell lines. Knockdown of DDX46 obviously inhibited osteosarcoma cell proliferation and tumor growth in vivo. In addition, knockdown of DDX46 also significantly suppressed migration and invasion in osteosarcoma cells. Furthermore, knockdown of DDX46 substantially downregulated the phosphorylation levels of PI3K and Akt in SaOS2 cells. In summary, the present results have revealed that DDX46 plays an important role in osteosarcoma growth and metastasis. Knockdown of DDX46 inhibited osteosarcoma cell proliferation, migration, and invasion in vitro and tumor growth in vivo. Therefore, DDX46 may be a potential therapeutic target for the treatment of osteosarcoma.

Key words: DDX46; Osteosarcoma; Metastasis; PI3K/Akt pathway

1These authors provided equal contribution to this work.
Address correspondence to Feng Jiang, Department of Orthopedics, Huaihe Hospital of Henan University, No. 8 Baobei Road, Kaifeng 475000, Henan Province, P.R. China. Tel: +86-0371-23906644; Fax: +86-0371-23906644; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 427-435, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14747300207374
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

miR-935 Promotes Liver Cancer Cell Proliferation and Migration by Targeting SOX7

Xiaorui Liu,*†1 Jingjing Li,*1 Zujiang Yu,* Juan Li,* Ranran Sun,* and Quancheng Kan

*Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China
†Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China
‡Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China

Hepatocellular carcinoma (HCC) is the most common cancer in the world. MicroRNAs (miRNAs) are a type of small noncoding RNA that can regulate the expression of target genes under physiological and pathophysiological conditions. Aberrant expression of microRNA-935 (miR-935) has been reported in cancer studies. However, its expression and mechanism in HCC remain unclear. In our study, we found that miR-935 was upregulated in liver cancer tissues and cells. Overexpression of miR-935 in liver cells promoted cell proliferation, tumorigenesis, and cell cycle progression, whereas inhibition of miR-935 reduced cell proliferation, tumorigenicity, and cell cycle progression. These changes in the properties of HCC cells were associated with upregulation of two well-known cellular G1/S transitional regulators: cyclin D1 and c-Myc. Additionally, we identified SOX7 as a direct target of miR-935. Overexpression of miR-935 inhibited SOX7 expression but promoted the levels of c-Myc and cyclin D1, which promotes cell proliferation and tumorigenesis; knockdown of miR-935 increased SOX7 level and inhibited c-Myc and cyclin D1 expression, whereas SOX7 silencing could promote cell proliferation, cell motility, and invasiveness in vitro. Our findings suggest that miR-935 represents a biomarker and a potential new target in HCC progression by suppressing SOX7 expression.

Key words: Liver cancer; MicroRNA-935 (miR-935); SOX7

1These authors provided equal contribution to this work.
Address correspondence to Quancheng Kan, M.D., Department of Pharmacy, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe E Road, Erqi, Zhengzhou, Henan 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. 25, pp. 437-444, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14747335734344
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Overexpression of SCUBE2 Inhibits Proliferation, Migration, and Invasion in Glioma Cells

Erkun Guo, Hongjiang Liu, and Xiaopeng Liu

Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, P.R. China Signal peptide CUB EGF-like domain-containing protein 2 (SCUBE2), a member of the SCUBE family of proteins, was recently found to play an important role in cancer development. However, little is known regarding its biological function in glioma. In the present study, we investigated the effect of SCUBE2 on glioma and explored its relevant mechanisms. The study showed that SCUBE2 had a low expression in glioma tissue and cell lines. SCUBE2 overexpression inhibited glioma cell proliferation in vitro and in vivo as well as suppressed glioma cell migration and invasion in vitro. Furthermore, we found that the Sonic hedgehog (Shh) signaling pathway was involved in the inhibitory effect of SCUBE2 overexpression on glioma cells. In light of the results obtained from our study, SCUBE2 may be regarded as a potential therapeutic target for glioma.

Key words: Signal peptide CUB EGF-like domain-containing protein 2 (SCUBE2); Proliferation; Migration; Invasion; Glioma

Address correspondence to Erkun Guo, Department of Neurosurgery, The Second Hospital of Hebei Medical University, No. 215 West Heping Road, Shijiazhuang 050000, Hebei, P.R. China. Tel: +86-0311-87046901; Fax: +86-0311-87046901; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 25, pp. 445-454, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14747368729786
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

Demethylation of Repressor Element-1 Silencing Transcription (REST) Suppresses the Malignant Phenotype of Breast Cancer via MMP9

Ying Liu,*† Hui Lv,‡ Xiaoying Wu,*§ Jun Zhou,¶ Ying Shi,# and Jifang Wen*†

*Department of Pathology, Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China
†Department of Pathology, School of Basic Medical Sciences, Central South University, Changsha, Hunan, P.R. China
‡University of Colorado Denver, Aurora, CO, USA
§Department of Medical Ultrastructure, School of Basic Medical Sciences, Central South University, Changsha, Hunan, P.R. China
¶Institute of Pathology, Department of Pathology, Xiangnan University, Chenzhou, Hunan, P.R. China
#Department of Pathology and Pathophysiology, Xiamen Medical College, Fujian, P.R. China

Breast cancer is the leading cause of cancer deaths in females all over the world, mainly resulting from metastasis. Previous studies have revealed that repressor element-1 (RE-1) silencing transcription (REST) acted as a tumor suppressor in breast cancer. However, the mechanism by which REST is regulated remains unknown, and its role in the metastasis in breast cancer cells remains unclear. In the present study, we showed that the expression of REST was lower in breast cancer samples than that of adjacent samples by immunohistochemical analysis, which may be due to hypermethylation of the REST promoter. Low REST levels are significantly associated with malignant progression in breast cancer patients. Additionally, we elucidated the functions of REST on proliferation and invasion in breast cancer cells. Lentivirus transfection was used to overexpress REST in human breast MDA-MB-231 cells. Then the biologic consequences of overexpressing REST in regard to cell proliferation, apoptosis, and invasion were determined. Furthermore, we also determined matrix metalloproteinase-9 (MMP9) as a target of REST. These results demonstrate that downregulation of REST, a tumor suppressor in breast cancer, is associated with hypermethylation. Induced REST expression is capable of attenuating invasion ability of breast cancer cells, which may be a novel strategy for metastatic breast cancer treatment.

Key words: Breast cancer; Repressor element-1 silencing transcription (REST); Methylation; Metastasis; Matrix metalloproteinase (MMP)

Address correspondence to Professor Jifang Wen, Department of Pathology, Xiangya Hospital and School of Basic Medical Sciences, Central South University, 87 Xiangya Road, Changsha, Hunan 410008, 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. 455-461, 2017
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14747283032017
E-ISSN 1555-3906
Copyright ©2017 Cognizant, LLC.
Printed in the USA. All rights reserved

MicroRNA-509-3p Inhibits Cancer Cell Proliferation and Migration via Upregulation of XIAP in Gastric Cancer Cells

Jihong Sun,*†1 Jingjing Li,‡1 Weiguo Zhang,* Juan Zhang,* Shenjie Sun,* Guiqi Li,* Hengliang Song,* and Daguo Wan*

*Department of Cardiology, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China
†Department of Gastroenterology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China
‡Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China

Gastric cancer (GC) is the fourth most common cancer globally. Recently, microRNAs (miRNAs) have been suggested to be closely associated with tumorigenesis. Aberrant expression of miR-509-3p has been reported in cancer studies. However, the expression and mechanism of its function in GC remain unclear. Here we showed that miR-509-3p was downregulated in GC specimens, which was associated with overall survival. Functional investigations demonstrated that the overexpression of miR-509-3p inhibited the migration and proliferation of the GC cells. Additionally, we identified X-linked inhibitor of apoptosis protein (XIAP) as a direct target of miR-509-3p. Knockdown of XIAP significantly attenuated the ability of proliferation, migration, and invasion of GC cells. The data therefore suggest that miR-509-3p plays an important role in the development and progression of GC, implicating possible applications in the clinic as a biomarker and a potential new target.

Key words: Gastric cancer (GC); MicroRNA-509-3p (miR-509-3p); X-linked inhibitor of apoptosis protein (XIAP)

1These authors provided equal contribution to this work.
Address correspondence to Daguo Wan, M.D., Department of Cardiology, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe E Road, Erqi, Zhengzhou, Henan 450052, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it