MiR-17-5p regulates cell proliferation and migration by targeting transforming growth factor-β receptor 2 in gastric cancer
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Yanjun Qu1,*, Haiyang Zhang1,*, Jingjing Duan1,*, Rui Liu1, Ting Deng1, Ming Bai1, Dingzhi Huang1, Hongli Li1, Tao Ning1, Le Zhang1, Xia Wang1, Shaohua Ge1, Likun Zhou1, Benfu Zhong1, Guoguang Ying1, Yi Ba1
1Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, 300060, China
*These authors have contributed equally to this work
Yi Ba, e-mail: [email protected]
Guoguang Ying, e-mail: [email protected]
Keywords: gastric cancer, TGFBR2, miR-17-5p, cell proliferation, migration
Received: December 16, 2015 Accepted: March 28, 2016 Published: April 23, 2016
TGFBR2 serves as an initial regulator of the TGF-β signaling pathway, and loss or reduction of its expression leads to uncontrolled cell growth and invasion. TGFBR2 plays a crucial role in the carcinogenesis and malignant process of gastric cancer, but the mechanism remains unclear. In this study, we found that TGFBR2 protein levels were consistently upregulated in gastric cancer tissues, whereas TGFBR2 mRNA levels varied among these tissues, indicating that a post-transcriptional mechanism is involved in the regulation of TGFBR2. MiRNAs are known to regulate gene expression at the post-transcriptional level. Therefore, we performed bioinformatics analyses to search for miRNAs potentially targeting TGFBR2. MiR-17-5p was found to bind to the 3’UTR of TGFBR2 mRNA, and further validation of this specific binding was performed through a reporter assay. An inverse correlation between miR-17-5p and TGFBR2 protein was observed in gastric cancer tissues. Cell studies revealed that miR-17-5p negatively regulated TGFBR2 expression by directly binding to the 3’UTR of TGFBR2 mRNA, thereby promoting cell growth and migration. We also validated the role of TGFBR2 using siRNA and an overexpression plasmid. The results of our study suggest a novel regulatory network in gastric cancer mediated by miR-17-5p and TGFBR2 and may indicate that TGFBR2 could serve as a new therapeutic target in gastric cancer.
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