Research Papers:

MicroRNA-638 inhibits cell proliferation, invasion and regulates cell cycle by targeting tetraspanin 1 in human colorectal carcinoma

Jiwei Zhang _, Bojian Fei, Qifeng Wang, Mingxu Song, Yuan Yin, Binbin Zhang, Shujuan Ni, Weijie Guo, Zehua Bian, Chao Quan, Zhihui Liu, Yugang Wang, Jian Yu, Xiang Du, Dong Hua and Zhaohui Huang

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Oncotarget. 2014; 5:12083-12096. https://doi.org/10.18632/oncotarget.2499

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Jiwei Zhang1,*, Bojian Fei2,*, Qifeng Wang3, Mingxu Song1, Yuan Yin1, Binbin Zhang1, Shujuan Ni3, Weijie Guo4, Zehua Bian1, Chao Quan1, Zhihui Liu1, Yugang Wang5, Jian Yu6, Xiang Du3, Dong Hua1, Zhaohui Huang1

1Wuxi Oncology Institute, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China

2Department of Surgical Oncology, the Affiliated Hospital of Jiangnan University, Wuxi, Jiangsu, 214062, China

3Department of Pathology, Fudan University Shanghai Cancer Center, Shanghai, 200032, China

4Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China

5Department of Urology, University of Michigan Comprehensive Cancer Center, Ann Arbor, MI 48109-5942, USA

6State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China

*These authors contributed equally to this work

Correspondence to:

Zhaohui Huang, e-mail: [email protected]

Keywords: microRNA-638, TSPAN1, cell proliferation, colorectal carcinoma, cell cycle

Received: July 19, 2014     Accepted: September 16, 2014     Published: October 07, 2014


The expression of miR-638 was found downregulated in colorectal carcinoma (CRC) in our previous study. However, the role of miR-638 in CRC remains unknown. The aim of this study was to determine the function and mechanism of miR-638 in CRC. Here, we verified that miR-638 was frequently downregulated in CRC tissues compared with corresponding noncancerous tissues (NCTs) in an expanded CRC cohort, and survival analysis showed that the downregulation of miR-638 in CRC was associated with poor prognoses. The ectopic expression of miR-638 inhibited CRC cell proliferation, invasion and arrest the cell cycle in G1 phase, whereas the repression of miR-638 significantly promoted CRC cell growth, invasion and cell cycle G1/S transition. Subsequent mechanism analyses revealed that miR-638 inhibited CRC cell growth, invasion and cell cycle progression by targeting TSPAN1. TSPAN1 protein levels were upregulated in CRC samples and were inversely correlated with miR-638 levels. More importantly, high TSPAN1 expression levels in CRC tissues predicted poor overall survival, and appears to be an independent prognostic factor for CRC survival. Furthermore, CpG island methylation analyses revealed that the miR-638 promoter was hypermethylated in CRC and that attenuating promoter methylation was sufficient to restore miR-638 expression in CRC cells. Taken together, our current data demonstrate that miR-638 functions as a tumor suppressor in human CRC by inhibiting TSPAN1, and that TSPAN1 is a potential prognostic factor for CRC.

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