Oncology Research 26(1) Abstracts

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Oncology Research, Vol. 26, pp. 1-8, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504016X
14772410356982
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

miR-644a Inhibits Cellular Proliferation and Invasion via Suppression of CtBP1 in Gastric Cancer Cells

Yingchao Li,* Xiaoni Yan,* Li Ren,* and Yang Li†

*Department of Gastroenterology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, P.R. China
†Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Medical School of Xi’an Jiaotong University, Xi’an, Shaanxi, P.R. China

Epithelial–mesenchymal transition (EMT) is one of the most important mechanisms in the metastasis of various cancers, including gastric cancer (GC). In
this study, we explored the putative significance of miR-644a and its role in EMT-mediated metastasis of GC. We first detected the expression of miR-644a in a cohort of 107 GC tissues using quantitative RT-PCR. The expression of miR-644a was suppressed in GC tissues and was associated with a later clinical stage and tumor metastasis. Restoring the expression of miR-644a could significantly suppress the migration and invasion of HGC-27 and SGC-7901 cells, which might be correlated to its suppressive effect on the EMT process. We also found that carboxyl-terminal-binding protein 1 (CtBP1) was a putative target gene of miR-644a in GC and might be involved in the suppressive effect. Collectively, through targeting CtBP1-mediated suppression of the EMT process, miR-644a might suppress the tumor metastasis of GC cells.

Key words: Gastric cancer (GC); Tumor metastasis; Carboxyl-terminal-binding protein 1 (CtBP1); Epithelial–mesenchymal transition (EMT) progression; miR-644a

Address correspondence to Dr. Yang Li, Department of Otolaryngology, Head and Neck Surgery, The Second Affiliated Hospital, Medical School of Xi’an Jiaotong University, No. 157 Xiwu Road, Xi’an, Shaanxi 710004, P.R. China. Tel: 86-29-87679272; Fax: 86-29-87679272; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 9-15, 2018
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DOI: https://doi.org/10.3727/096504017X
14871200709504
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

RBMS3 Inhibits the Proliferation and Metastasis of Breast Cancer Cells

Yuan Yang,* Lingli Quan,† and Ye Ling*

*The Second Xiangya Hospital of Central South University, Changsha, P.R. China
†The First Department of Respiratory Medicine, Zhuzhou Central Hospital, Zhuzhou, P.R. China

RBMS3, a gene encoding a glycine-rich RNA-binding protein, belongs to the family of c-Myc gene single-strand binding proteins (MSSP). Recently, several reports have provided evidence that RBMS3 was deregulated in a diverse range of solid tumors and played a critical role in tumor progression. However, it remains unclear whether RBMS3 inhibits the progression of human breast cancer. Thus, the aim of this study was to investigate the role of RBMS3 in breast cancer and explore the underlying mechanism in breast cancer progression. Our results showed, for the first time, that the expression of RBMS3 at both the mRNA and protein levels was significantly downregulated in human breast cancer tissues and cell lines. In addition, RBMS3 overexpression dramatically suppressed the proliferation, migration, and invasion of breast cancer cells in vitro and attenuated tumor growth in vivo. Furthermore, we observed that RBMS3 greatly inhibited the protein expression of β-catenin, cyclin D1, and c-Myc in breast cancer cells. In summary, we have shown that RBMS3 inhibited the proliferation and tumorigenesis of breast cancer cells, at least in part, through inactivation of the Wnt/β-catenin signaling pathway. Thus, RBMS3 may be a potential treatment target for breast cancer.

Key words: RBMS3; Breast cancer; Metastasis; Tumorigenesis; Wnt/β-catenin signaling

Address correspondence to Lingli Quan, The First Department of Respiratory Medicine, Zhuzhou Central Hospital, 116 Changjiang South Road, Zhuzhou 412000, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Ye Ling, The Second Xiangya Hospital of Central South University, 139 Renmin Road, Changsha 410011, 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. 17-26, 2018
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DOI: https://doi.org/10.3727/096504017X
14881490607028
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Analysis of MicroRNA–mRNA Interactions in Stem Cell-Enriched Fraction of Oral Squamous Cell Carcinoma

Vinitha Richard, Rajesh Raju, Aswathy Mary Paul, Reshmi GirijadeviThankayyan Retnabai Santhosh Kumar, and Madhavan Radhakrishna Pillai

Cancer Research Program, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala State, India

This study is an integrated analysis of the transcriptome profile microRNA (miRNA) and its experimentally validated mRNA targets differentially expressed in the tumorigenic stem-like fraction of oral squamous cell carcinoma (OSCC). We had previously reported the coexistence of multiple drug-resistant tumorigenic fractions, termed side population (SP1, SP2, and MP2), and a nontumorigenic fraction, termed main population (MP1), in oral cancer. These fractions displayed a self-renewal, regenerative potential and expressed known stemness-related cell surface markers despite functional differences. Flow cytometrically sorted pure fractions of SP1 and MP1 cells were subjected to differential expression analysis of both mRNAs and miRNAs. A significant upregulation of genes associated with inflammation, cell survival, cell proliferation, drug transporters, and antiapoptotic pathways, in addition to enhanced transcriptome reprogramming mediated by DNA–histone binding proteins and pattern recognition receptor-mediated signaling, was found to play a crucial role in the transformation of the nontumorigenic MP1 fraction to the tumorigenic SP1 fraction. We also identified several differentially expressed miRNAs that specifically target genes distinctive of tumorigenic SP1 fraction. miRNA-mediated downregulation of stemness-associated markers CD44 and CD147 and upregulation of CD151 may also account for the emergence and persistence of multiple tumorigenic stem cell fractions with varying degrees of malignancy. The phenotypic switch of cancer cells to stem-like OSCC cells mediated by transcriptomal regulation is effectual in addressing biological tumor heterogeneity and subsequent therapeutic resistance leading to a minimal residual disease (MRD) condition in oral cancer. A detailed study of the interplay of miRNAs, mRNA, and the cellular phases involved in the gradual transition of nontumorigenic cancer cells to tumorigenic stem-like cells in solid tumors would enable detection and development of a treatment regimen that targets and successfully eliminates multiple, drug-resistant fractions of cancer cells.

Key words: Cancer stem cells (CSCs); Oral cancer; Side population (SP); Tumorigenic; MicroRNAs (miRNAs)

Address correspondence to Professor M. Radhakrishna Pillai, FRCPath, Ph.D., Director and Head of Cancer Research, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram 695014, India. Tel: +91 471 2347973; Fax: +91 471 2349303; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 27-35, 2018
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DOI: https://doi.org/10.3727/096504017X
14900515946914
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

G-Protein Signaling Protein-17 (RGS17) Is Upregulated and Promotes Tumor Growth and Migration in Human Colorectal Carcinoma

Ling Li and He-Sheng Luo

Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, P.R. China

Colorectal carcinoma is one of the leading causes of cancer-related deaths and has a high tendency for metastasis, which makes it a priority to find novel methods to diagnose and treat colorectal carcinoma at a very early stage. We studied the role of the regulator of G-protein signaling (RGS) family of proteins RGS17 in colorectal carcinoma growth and metastasis. We found that RGS17 was upregulated in both clinical colorectal carcinoma tissues and cultured colorectal carcinoma cells. Knockdown of RGS17 by specific siRNA decreased the cell proliferation rate, whereas overexpression of RGS17 with expression plasmid increased the rate in cultured cells. Consistently, a mouse model for colorectal carcinoma also showed that depletion of RGS17 significantly inhibited tumor growth in vivo. Moreover, a Transwell assay showed that RGS17 promoted the ability of colorectal carcinoma cells to migrate and invade. These data suggest that RGS17 is overexpressed in colorectal carcinoma and promotes cell proliferation, migration, and invasion.

Key words: RGS17; Colorectal carcinoma; Cell growth; Migration; Invasion

Address correspondence to He-Sheng Luo, Department of Gastroenterology, Renmin Hospital of Wuhan University, 5 Zhangzhidong Road, Nanchang District, Wuhan, Hubei Province 430060, 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. 37-44, 2018
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DOI: https://doi.org/10.3727/096504017X
14900530835262
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Knockdown of Homeobox B5 (HOXB5) Inhibits Cell Proliferation, Migration, and Invasion in Non-Small Cell Lung Cancer Cells Through Inactivation of the Wnt/β-Catenin Pathway

Bin Zhang,1 Na Li,1 and Hao Zhang

Department of Respiratory Disease, The Second Affiliated Hospital of Zhejiang University, School of Medicine, Hangzhou, Zhejiang Province, P.R. China

Homeobox B5 (HOXB5), a member of the HOX gene family, has been shown to play an important role in tumor progression. However, the expression and functional role of HOXB5 in human non-small cell lung cancer (NSCLC) have not been defined. Thus, the purpose of this study was to elucidate the expression and functional role of HOXB5 in human NSCLC. Our results showed that HOXB5 expression was elevated in human NSCLC tissues and cell lines. The in vitro experiments demonstrated that knockdown of HOXB5 inhibited proliferation, migration, and invasion and prevented the EMT phenotype in NSCLC cells. In vivo experiments indicated that knockdown of HOXB5 attenuated the growth of NSCLC xenografts in vivo. Furthermore, knockdown of HOXB5 suppressed the protein expression levels of β-catenin and its downstream targets c-Myc and cyclin D1 in A549 cells. Taken together, for the first time we have shown that knockdown of HOXB5 significantly inhibited NSCLC cell proliferation, invasion, metastasis, and EMT, partly through the Wnt/β-catenin signaling pathway. These findings suggest that HOXB5 may be a novel therapeutic target for the treatment of NSCLC.

Key words: Homeobox B5 (HOXB5); Non-small cell lung cancer (NSCLC); Invasion; Wnt/β-catenin pathway

1These authors provided equal contribution to this work.
Address correspondence to Hao Zhang, Department of Respiratory Disease, The Second Affiliated Hospital of Zhejiang University, School of Medicine, No. 88 Jiefang Road, Hangzhou 310009, Zhejiang Province, P.R. China. Tel: +86-0571-87783777; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 45-58, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14926874596386
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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DKK3 Overexpression Increases the Malignant Properties of Head and Neck Squamous Cell Carcinoma Cells

Naoki Katase,*† Shin-Ichiro Nishimatsu,†‡ Akira Yamauchi,§ Masahiro Yamamura,¶ Kumiko Terada,†‡ Masumi Itadani,§ Naoko Okada,¶# Nur Mohammad Monsur Hassan,** Hitoshi Nagatsuka,†† Tohru Ikeda,*‡‡ Tsutomu Nohno,† and Shuichi Fujita*

*Department of Oral Pathology and Bone Metabolism, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
†Department of Molecular and Developmental Biology, Kawasaki Medical School, Kurashiki, Okayama, Japan
‡Department of Natural Sciences, Kawasaki Medical School, Kurashiki, Okayama, Japan
§Department of Biochemistry, Kawasaki Medical School, Kurashiki, Okayama, Japan
¶Department of Clinical Oncology, Kawasaki Medical School, Kurashiki, Okayama, Japan
#Department of Surgery, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki, Japan
**School of Dentistry and Health Sciences, Charles Sturt University, Orange, New South Wales, Australia
††Department of Oral Pathology and Medicine, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Okayama, Japan
‡‡Department of Oral Pathology, Tokyo Medical and Dental University, Tokyo, Japan

DKK3, a member of the dickkopf Wnt signaling pathway inhibitor family, is believed to be a tumor suppressor because of its reduced expression in cancer cells. However, our previous studies have revealed that DKK3 expression is predominantly observed in head and neck/oral squamous cell carcinoma (HNSCC/OSCC). Interestingly, HNSCC/OSCC patients with DKK3 expression showed a high rate of metastasis and poorer survival, and siRNA-mediated knockdown of DKK3 in HNSCC-derived cancer cell lines resulted in reduced cellular migration and invasion. From these data, it was hypothesized that DKK3 might exert an oncogenic function specific to HNSCC. In the present research, the DKK3 overexpression model was established, and its influences were investigated, together with molecular mechanism studies. The DKK3 expression profile in cancer cell lines was investigated, including HNSCC/OSCC, esophageal, gastric, colorectal, pancreatic, prostatic, and lung cancers. DKK3 overexpression was performed in HNSCC-derived cells by transfection of expression plasmid. The effects of DKK3 overexpression were assessed on cellular proliferation, migration, invasion, and in vivo tumor growth. The molecular mechanism of DKK3 overexpression was investigated by Western blotting and microarray analysis. DKK3 overexpression significantly elevated cellular proliferation, migration, and invasion, as well as increased mRNA expression of cyclin D1 and c-myc. However, reporter assays did not show TCF/LEF activation, suggesting that the increased malignant property of cancer cells was not driven by the Wnt/β-catenin pathway. For the investigation of the pathways/molecules in DKK3-mediated signals, the Western blot analyses revealed that phosphorylation of Akt (S473) and c-Jun (Ser63) was elevated. The application of a PI3K kinase inhibitor, LY294002, on HSC-3 DKK3 cells significantly decreased tumor cell proliferation, migration, and invasion. From these results, we demonstrated that DKK3 might contribute to cellular proliferation, invasion, migration, and tumor cell survival in HNSCC cells through a mechanism other than the canonical Wnt signaling pathway, which might be attributed to PI3K–Akt signaling.

Key words: Head and neck squamous cell carcinoma (HNSCC); Oral cancer; DKK3; Wnt signaling

Address correspondence to Naoki Katase, D.D.S., Ph.D., Department of Oral Pathology and Bone Metabolism, Graduate School of Biomedical Sciences, Sakamoto 1-7-1, Nagasaki 852-8588, Japan. Tel: +81-95-819-7646; Fax: +81-95-819-7647; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 59-69, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14913452320194
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Erlotinib-Associated Rash in Advanced Non-Small Cell Lung Cancer: Relation to Clinicopathological Characteristics, Treatment Response, and Survival

Ilias Kainis,* Nikolaos Syrigos,* Alexandra Kopitopoulou,* Ioannis Gkiozos,* Effrosyni Filiou,* Vasiliki Nikolaou,* and Evangelia Papadavid

*3rd Department of Medicine, Athens Medical School, National and Kapodistrian University of Athens, Athens, Greece
†2nd Department of Dermatology Venereology, Attikon General University Hospital, Athens, Greece

Systematic treatment of advanced non-small cell lung cancer (NSCLC) includes targeted treatment with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs). The development of skin rash and its intensity have been associated with EGFR TKI’s efficacy. The main purpose of this study was to further investigate the potential value of erlotinib-associated rash as a predictor of prognosis and treatment response in a real-world cohort of patients with advanced NSCLC. The medical records of all NSCLC patients treated with erlotinib at the Oncology Unit of GPP, Sotiria Athens General Hospital between January 1, 2014 and August 31, 2016 were retrospectively reviewed. Seventy-nine patient medical records fulfilled the criteria and were included in the study. Development of erlotinib-associated rash was correlated with clinicopathological characteristics of patients, treatment response, and overall survival (OS) using univariate and multivariate Cox regression analysis. The number of patients with rash was greater in the responders group (90% vs. 46.4%, p = 0.015). In univariate analysis, there was a statistically significant association between rash development and time to progression (TTP) [HR: 0.32 (0.17–0.57), p < 0.001]. With multivariate Cox regression analysis, it was found that PS ≥ 2 (HR: 2.01, 95% CI: 1.12–3.60, p = 0.018) and rash (HR: 0.34, 95% CI: 0.18–0.63, p = 0.001) were independently associated with TTP and also that the duration of treatment with erlotinib (HR: 0.58, 95% CI: 0.42–0.80, p = 0.001) and rash (HR: 0.10, 95% CI: 0.20–0.48, p = 0.004) was an independent predictor of survival. Our results suggest that erlotinib-associated rash may represent a clinically valuable biomarker for the prediction of treatment response and OS in patients with advanced NSCLC.

Key words: Erlotinib; Rash; Non-small cell lung cancer (NSCLC); Response

Address correspondence to Alexandra Kopitopoulou, 3rd Department of Medicine, Athens Medical School, National and Kapodistrian University of Athens, Mesogeion 152, 11527 Athens, Greece. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 71-81, 2018
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DOI: https://doi.org/10.3727/096504017X
14902648894463
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Regulation of Acetate Utilization by Monocarboxylate Transporter 1 (MCT1) in Hepatocellular Carcinoma (HCC)

Jeong Yong Jeon,*1 Misu Lee,*†1 Sang Hyun Whang,* Jung-Whan Kim,‡ Arthur Cho,* and Mijin Yun*

*Department of Nuclear Medicine, Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
†Division of Life Science, College of Life Science and Bioengineering, Incheon National University, Incheon, South Korea
‡Department of Biological Sciences, The University of Texas at Dallas, Richardson, TX, USA

Altered energy metabolism is a biochemical fingerprint of cancer cells. Hepatocellular carcinoma (HCC) shows reciprocal [18F]fluorodeoxyglucose (FDG) and [11C]acetate uptake, as revealed by positron emission tomography/computed tomography (PET/CT). Previous studies have focused on the role of FDG uptake in cancer cells. In this study, we evaluated the mechanism and roles of [11C]acetate uptake in human HCCs and cell lines. The expression of monocarboxylatetransporters (MCTs) was assessed to determine the transporters of [11C]acetate uptake in HCC cell lines and human HCCs with different [11C]acetate uptake. Using two representative cell lines with widely different [11C]acetate uptake (HepG2 for high uptake and Hep3B for low uptake), changes in [11C]acetate uptake were measured after treatment with an MCT1 inhibitor or MCT1-targeted siRNA. To verify the roles of MCT1 in cells, oxygen consumption rate and the amount of lipid synthesis were measured. HepG2 cells with high [11C]acetate uptake showed higher MCT1 expression than other HCC cell lines with low [11C]acetate uptake. MCT1 expression was elevated in human HCCs with high [11C]acetate uptake compared to those with low [11C]acetate uptake. After blocking MCT1 with AR-C155858 or MCT1 knockdown, [11C]acetate uptake in HepG2 cells was significantly reduced. Additionally, inhibition of MCT1 suppressed mitochondrial oxidative phosphorylation, lipid synthesis, and cellular proliferation in HCC cells with high [11C]acetate uptake. MCT1 may be a new therapeutic target for acetate-dependent HCCs with high [11C]acetate uptake, which can be selected by [11C]acetate PET/CT imaging in clinical practice.

Key words: [11C]Acetate uptake; Hepatocellular carcinoma (HCC); Monocarboxylate transporter (MCT); Positron emission tomography/computed tomography (PET/CT)

1These authors provided equal contribution to this work.
Address correspondence to Mijin Yun, M.D., Department of Nuclear Medicine, Yonsei University College of Medicine, 50-1 Yonsei-Ro, Seodaemun-GuSeoul 03722, South Korea. Tel: +82 2 2228-6068; Fax: + 82 2 312-0578; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 83-93, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14928634401204
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Cathepsin F Knockdown Induces Proliferation and Inhibits Apoptosis in Gastric Cancer Cells

Ce Ji,* Ying Zhao,* You-Wei Kou,* Hua Shao,* Lin Guo,* Chen-Hui Bao,* Ben-Chun Jiang,* Xin-Ying Chen,* Jing-Wei Dai,† Yu-Xin Tong,‡ Ren Yang,* Wei Sun,* and Qiang Wang*

*Department of Gastrointestinal and Nutrition Surgery, Shengjing Hospital of China Medical University, Shenyang, P.R. China
†Department of Pancreatic and Thyroidal Surgery, Shengjing Hospital of China Medical University, Shenyang, P.R. China
‡Medical Research Center, Shengjing Hospital of China Medical University, Shenyang, P.R. China

Gastric cancer (GC) is one of the most common cancers in the world. The cathepsin F (CTSF) gene has recently been found to participate in the progression of several types of cancer. However, the clinical characteristics and function of CTSF in GC as well as its molecular mechanisms are not clear. Six GC cell lines and 44 paired adjacent noncancerous and GC tissue samples were used to assess CTSF expression by quantitative polymerase chain reaction (qPCR). We used lentivirus-mediated small hairpin RNA (Lenti-shRNA) against CTSF to knock down the expression of CTSF in GC cells. Western blot and qPCR were used to analyze the mRNA and related protein expression. The biological phenotypes of gastric cells were examined by cell proliferation and apoptosis assays. Microarray-based mRNA expression profile screening was also performed to evaluate the potential molecular pathways in which CTSF may be involved. The CTSF mRNA level was associated with tumor differentiation, depth of tumor invasion, and lymph node metastasis. Downregulation of CTSF expression efficiently inhibited apoptosis and promoted the proliferation of GC cells. Moreover, a total of 1,117 upregulated mRNAs and 1,143 downregulated mRNAs were identified as differentially expressed genes (DEGs). Further analysis identified the involvement of these mRNAs in cancer-related pathways and various other biological processes. Nine DEGs in cancer-related pathways and three downstream genes in the apoptosis pathway were validated by Western blot, which was mainly in agreement with the microarray data. To our knowledge, this is the first report investigating the effect of CTSF on the growth and apoptosis in GC cells and its clinical significance. The CTSF gene may function as a tumor suppressor in GC and may be a potential therapeutic target in the treatment of GC.

Key words: Gastric cancer (GC); Cathepsin F (CTSF); Proliferation; Apoptosis; Microarray

Address correspondence to Qiang Wang, Department of Gastrointestinal and Nutrition Surgery, Shengjing Hospital of China Medical University, No. 36 Sanhao Street, Heping District, Shenyang, P.R. China. Tel: +86-024-96615; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 95-101, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14920318811695
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Knockdown of TMPRSS3, a Transmembrane Serine Protease, Inhibits Proliferation, Migration, and Invasion in Human Nasopharyngeal Carcinoma Cells

Jun-Ying Wang,* Xin Jin,* and Xiao-Feng Li†

*Department of ENT, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu, P.R. China
†Department of Ophthalmology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, Jiangsu, P.R. China

TMPRSS3 belongs to the large type II transmembrane serine protease (TTSP) family, which plays an important role in the development and progression of tumors. However, the function of TMPRSS3 in nasopharyngeal carcinoma (NPC) remains unclear. The present study aimed to examine the impact of TMPRSS3 on the proliferation, migration, and invasion of NPC cells and their potential mechanisms. Our results demonstrated that the expression of TMPRSS3 was obviously upregulated in human NPC tissues and cell lines. Knockdown of TMPRSS3 expression significantly suppressed the proliferation and tumorigenicity of NPC cells in vitro and in vivo. Furthermore, knockdown of TMPRSS3 inhibited migration and invasion, as well as prevented the EMT process in NPC cells. Finally, knockdown of TMPRSS3 attenuated activation of the PI3K/Akt signaling pathway in NPC cells. Taken together, the present study demonstrates that the knockdown of TMPRSS3 inhibits proliferation, migration, and invasion in human NPC cells through the inactivation of the PI3K/Akt signaling pathway. This study suggests that TMPRSS3 may be a potential therapeutic target for the treatment of NPC.

Key words: Nasopharyngeal carcinoma (NPC); TMPRSS3; Invasion; PI3K/Akt pathway

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


Oncology Research, Vol. 26, pp. 103-110, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14934860122864
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Long Noncoding RNA UCA1 Targets miR-122 to Promote Proliferation, Migration, and Invasion of Glioma Cells

Yang Sun,*1 Jun-Gong Jin,*1 Wei-Yang Mi,† Hao-Wu,* Shi-Rong Zhang,‡ Qiang Meng,* and Shi-Tao Zhang‡

*Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, Xi’an, P.R. China
†Department of Neurosurgery, Xi’an Children’s Hospital, Xi’an, P.R. China
‡Department of Neurosurgery, Xi’an No. 3 Hospital, Xi’an, P.R. China

Glioma is the most common and lethal malignant intracranial tumor. Long noncoding RNAs (lncRNAs) have been identified as pivotal regulators in the tumorigenesis of glioma. However, the role of lncRNA urothelial carcinoma-associated 1 (UCA1) in glioma genesis is still unknown. The purpose of this study was to investigate the underlying function of UCA1 on glioma genesis. The results demonstrated that UCA1 was upregulated in glioma tissue and indicated a poor prognosis. UCA1 knockdown induced by si-UCA1 significantly suppressed the proliferative, migrative, and invasive activities of glioma cell lines (U87 and U251). Bioinformatics analysis and luciferase reporter assay verified the complementary binding within UCA1 and miR-122 at the 3ʹ-UTR. Functional experiments revealed that UCA1 acted as an miR-122 “sponge” to modulate glioma cell proliferation, migration, and invasion via downregulation of miR-122. Overall, the present study demonstrated that lncRNA UCA1 acts as an endogenous sponge of miR-122 to promote glioma cell proliferation, migration, and invasion, which provides a novel insight and therapeutic target in the tumorigenesis of glioma.

Key words: Glioma; Long noncoding RNAs (lncRNAs); Urothelial carcinoma-associated 1 (UCA1); miR-122; Migration; Invasion

1These authors are co-first authors.
Address correspondence to Shi-Tao Zhang, Department of Neurosurgery, Xi’an No. 3 Hospital, No. 10 Fengcheng Road, Weiyang District, Xi’an 710018, P.R. China. E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Qiang Meng, Department of Neurosurgery, Tangdu Hospital, Fourth Military Medical University, No. 1 Xinsi Road, Baqiao District, Xi’an, 710032, 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. 111-122, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14924753593574
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
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Increased Expression of Cullin 3 in Nasopharyngeal Carcinoma and Knockdown Inhibits Proliferation and Invasion

Ruifang Zeng, Guolin Tan, Wei Li, and Yanhong Ma

Department of Otolaryngology/Head and Neck Surgery, Third Xiangya Hospital, Central South University, Changsha, Hunan, P.R. China

This study aimed to investigate the clinical significance of cullin 3 expression in nasopharyngeal carcinoma (NPC), as well as to explore the regulatory mechanism of cullin 3 underlying the growth and metastasis of NPC cells. Our findings showed that the expression levels of cullin 3 were significantly increased in both NPC tissues and cell lines. A strong positive correlation was found between cullin 3 expression and the Ki-67-based proliferation index in NPC tissues. Moreover, cullin 3 overexpression was correlated with local relapse and distant metastasis in NPC patients. In vitro experiments showed that knockdown of cullin 3 caused a significant reduction in the proliferation of NPC cells, probably by inducing cell cycle arrest. In addition, downregulation of cullin 3 inhibited colony formation and the migratory and invasive capacities of NPC cells. The expression levels of PCNA and epithelial-to-mesenchymal transition (EMT)-related proteins were also meditated by cullin 3 in NPC cells. Based on these findings, we demonstrated that cullin 3 plays a promoting role in the malignant progression of NPC and suggest that the cullin 3-based ubiquitin proteasome pathway may be used as a promising therapeutic target for NPC.

Key words: Cullin 3; Nasopharyngeal carcinoma (NPC); Tumor progression; Prognosis; Survival

Address correspondence to Professor Guolin Tan, Department of Otolaryngology/Head and Neck Surgery, Third Xiangya Hospital of Central South University, 138 Tongzipo Road, Yuelu District, Changsha, Hunan 410013, P.R. China. Tel: +86-731-88618024; Fax: +86-731-88618536; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 123-130, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14912172235777
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Knockdown of Rap2B, a Ras Superfamily Protein, Inhibits Proliferation, Migration, and Invasion in Cervical Cancer Cells via Regulating the ERK1/2 Signaling Pathway

Yinghua Li,*† Songyi Li,† and Lili Huang*

*Department of Gynecology and Obstetrics, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, P.R. China
†Department of Gynecology and Obstetrics, Women’s Hospital of Hangzhou City, Hangzhou, P.R. China

Rap2B, belonging to the Ras superfamily, has been implicated in cancer development and functions as a tumor promoter. However, the role of Rap2B in cervical cancer is unknown. In this study, we investigated the expression pattern and biological functions of Rap2B in cervical cancer. The results showed that Rap2B was overexpressed in cervical cancer tissues and cell lines. Knockdown of Rap2B inhibited the proliferation, migration, and invasion of cervical cancer cells. In addition, our tumorigenesis assay showed that Rap2B knockdown suppressed cervical cancer cell growth and metastasis in vivo. We also found that the ERK1/2 signaling pathway is involved in the inhibitory effect of Rap2B knockdown on cervical cancer development. In conclusion, we suggest that Rap2B is an oncogene and may be a promising therapeutic target for cervical cancer.

Key words: Rap2B; Proliferation; Migration; Invasion; Cervical cancer

Address correspondence to Lili Huang, Women’s Hospital, School of Medicine, Zhejiang University, No. 1 Xueshi Road, Hangzhou 310006, Zhejiang, P.R. China. Tel: +86-571-87061501; Fax: +86-571-87061878; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 131-143, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14944585873631
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

Long Noncoding RNA SChLAP1 Accelerates the Proliferation and Metastasis of Prostate Cancer via Targeting miR-198 and Promoting the MAPK1 Pathway

Ye Li,*†‡ Haihong Luo,§ Nan Xiao,Jianmin Duan,Zhiping Wang,and Shuanke Wang

*Department of Urology, Lanzhou University Second Hospital, Lanzhou, P.R. China
†Key Laboratory of Urological Diseases, Lanzhou University, Lanzhou, P.R. China
‡Gansu Nephro-Urological Clinical Center, Lanzhou, P.R. China
§Department of Medical Services, Lanzhou University Second Hospital, Lanzhou, P.R. China
¶Department of Orthopedics, Lanzhou University Second Hospital, Lanzhou, P.R. China

Prostate cancer has become the most commonly diagnosed and the second leading cause of cancer-related deaths in males. The long noncoding RNA second chromosome locus associated with prostate-1 (SChLAP1) has been found to be overexpressed in a subset of prostate cancer. However, the significance and mechanism of SChLAP1 in prostate cancer are not well known. In this study, we explored the role of SChLAP1 in prostate cancer tissues, cell lines, and mouse models. The effect of SChLAP1 on miR-198 and MAPK1 was specifically examined. We found that SChLAP1 expression was significantly increased in prostate cancer cells and tissues. Knockdown of SChLAP1 promoted apoptosis and inhibited cell proliferation and invasion in vitro and in vivo. In addition, a potential bonding site between miR-198 and SChLAP1 was predicted, and a low expression of miR-198 was found in prostate cancer tissues and cells. Knockdown of SChLAP1 significantly increased the expression of miR-198, and SChLAP1 overexpression markedly decreased it, indicating that SChLAP1 acted as a negative regulator in the expression of miR-198. Furthermore, our results showed that SChLAP1 interacted with miR-198 and subsequently modulated the MAPK1 signaling pathway in prostate cancer. In conclusion, our study has identified a novel pathway through which SChLAP1 exerts its oncogenic role in prostate cancer at the level of miRNAs and provided a molecular basis for potential applications of SChLAP1 in the prognosis and treatment of prostate cancer.

Key words: Second chromosome locus associated with prostate-1 (SChLAP1); miR-198; MAPK1; Prostate cancer

Address correspondence to Shuanke Wang, Department of Orthopedics, Lanzhou University Second Hospital, No. 82 CuiyingmenChengguan District, 730030 Lanzhou, Gansu, P.R. China. Tel: (+86)0931-8943701; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it


Oncology Research, Vol. 26, pp. 145-155, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
14902261600566
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

MicroRNA-940 Targets INPP4A or GSK3β and Activates the Wnt/β-Catenin Pathway to Regulate the Malignant Behavior of Bladder Cancer Cells

Rong Wang, Yunfeng Wu, Weihua Huang, and Weijun Chen

Department of Urology, The Jintan Hospital Affiliated with Jiangsu University, Changzhou, Jiangsu, P.R. China

In this report, we aimed to explore the role and regulatory mechanism of microRNA-940 (miR-940) in bladder cancer development. The expressions of miR-940 in bladder cancer tissues and cells were measured. miR940 mimics, miR-940 inhibitor small interference RNA against INPP4A (si-INPP4A), and GSK3β (si-GSK3β) and their corresponding controls were then transfected into cells. We investigated the effects of miR-940, INPP4A, or GSK3β on cell proliferation, migration, invasion, and apoptosis. Additionally, target prediction and luciferase reporter assays were performed to investigate the targets of miR-940. The regulatory relationship between miR-940 and the Wnt/β-catenin pathway was also investigated. miR-940 was upregulated in bladder cancer tissues and cells. Overexpression of miR-940 significantly increased bladder cancer cell proliferation, promoted migration and invasion, and inhibited cell apoptosis. INPP4A and GSK3β were the direct targets of miR-940, and knockdown of INPP4A or GSK3β significantly increased cancer cell proliferation, migration, and invasion and inhibited cell apoptosis. After miR-940 overexpression, the protein expression levels of c-Myc, cyclin D1, and β-catenin were significantly increased, and the expression levels of p27 and p-β-catenin were markedly decreased. The opposite effects were obtained after suppression of miR-940. XAV939, a tankyrase 1 inhibitor that could inhibit Wnt/β-catenin signaling, significantly reversed the effects of miR-940 overexpression on cell migration and invasion. Our results indicate that overexpression of miR-940 may promote bladder cancer cell proliferation, migration, and invasion and inhibit cell apoptosis via targeting INPP4A or GSK3β and activating the Wnt/β-catenin pathway. Our findings imply the key roles of suppressing miRNA-940 in the therapy of bladder cancer.

Key words: Bladder cancer; miR-940; INPP4A; GSK3b; Wnt/β-catenin pathway

Address correspondence to Rong Wang, Department of Urology, The Jintan Hospital Affiliated with Jiangsu University, No. 16 South Gate Street, Jintan, Jiangsu 213200, 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. 156-171, 2018
0965-0407/17 $90.00 +.00
DOI: https://doi.org/10.3727/096504017X
15031557924150
E-ISSN 1555-3906
Copyright ©2018 Cognizant, LLC.
Printed in the USA. All rights reserved.

miR-216a-3p Inhibits the Proliferation, Migration, and Invasion of Human Gastric Cancer Cells via Targeting RUNX1 and Activating the NF-κBSignaling Pathway

Yinfang Wu,* Jun Zhang,† Yu Zheng,‡ Cheng Ma,‡ Xing-E Liu,§ and Xiaodong Sun*‡

*The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province, P.R. China
†Department of Gastroenterology, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang Province, P.R. China
‡Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang Province, P.R. China
§Department of Medical Oncology, Zhejiang Hospital, Hangzhou, Zhejiang Province, P.R. China

This work aims to elucidate the effects and the potential underlying mechanisms of microRNA-216a-3p (miR-216a-3p) on the proliferation, migration, and invasion of gastric cancer (GC) cells. In this study, we revealed that the expression of miR-216a-3p was significantly elevated in GC tissues and cell lines. The different expression level of miR-216a-3p was firmly correlated with clinicopathological characteristics of GC patients. We next demonstrated that upregulation of miR-216a-3p could dramatically promote the ability of proliferation, migration, and invasion of GC cells using a series of experiments, whereas downregulation essentially inhibited these properties. Additionally, through bioinformatics analysis and biological approaches, we confirmed that runt-related transcription factor 1 (RUNX1) was a direct target of miR-216a-3p, and overexpression of RUNX1 could reverse the potential effect of miR-216a-3p on GC cells. Furthermore, mechanistic investigation using Western blot analysis showed that downregulation of RUNX1 by miR-216a-3p could stimulate the activation of NF-κB signaling pathway. In summary, this work proved that miR-216a-3p can promote GC cell proliferation, migration, and invasion via targeting RUNX1 and activating the NF-κB signaling pathway. Therefore, miR-216a-3p/RUNX1 could be a possible molecular target for innovative therapeutic agents against GC.

Key words: Gastric cancer (GC); miR-216a-3p; RUNX1; NF-κB signaling pathway; Proliferation; Migration and invasion

Address correspondence to Dr. Xiaodong Sun, Department of Hepatobiliary and Pancreatic Surgery, Zhejiang Provincial People’s Hospital, No. 158 Shangtang Road, Hangzhou 310000, Zhejiang Province, P.R. China. Tel: 0086-571-85893311; Fax: 0086-571-85131448; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it  or Dr. Xing-E Liu, Department of Medical Oncology, Zhejiang Hospital, No. 12 Lingyin Road, Hangzhou 310000, Zhejiang Province, P.R. China. Tel: 0086-571-87987373; Fax: 0086-571-85131448; E-mail: This e-mail address is being protected from spambots. You need JavaScript enabled to view it