Methylation-induced downregulation and tumor suppressive role of microRNA-29b in gastric cancer through targeting LASP1
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Hui Li1, Guoqing Liu2, Ke Pan2, Xiongying Miao2 and Yong Xie2
1Department of Anesthesia, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
2Department of General Surgery, Second Xiangya Hospital, Central South University, Changsha, Hunan, China
Yong Xie, email: [email protected]
Keywords: gastric cancer; microRNA; methylation; LIM and SH3 protein 1
Received: May 12, 2017 Accepted: August 21, 2017 Published: September 30, 2017
MicroRNAs (miRs) have been demonstrated to play promoting or tumor suppressive roles in various human cancers, but the regulatory mechanism of miR-29b underlying gastric cancer development and progression still remains largely unclear. In the present study, we found that miR-29b was significantly downregulated in gastric cancer tissues and cell lines. Low expression of miR-29b was significantly associated with DNA methylation, and treatment with DNA methyltransferase inhibitor 5-Aza-20-deoxycytidine upregulated miR-29b in gastric cancer cells. In addition, both reduced miR-29b expression and miR-29b methylation were associated with disease progression and poor prognosis in gastric cancer. Restoration of miR-29b caused a reduction in gastric cancer cell proliferation, migration, and invasion, and inhibited tumor growth in vivo. LASP1 was then identified as a target gene of miR-29b in gastric cancer cells. Moreover, upregulation of LASP1 was significantly associated with gastric cancer progression and poor prognosis. Knockdown of LASP1 also suppressed the proliferation, migration, and invasion of gastric cancer cells. Moreover, overexpression of LASP1 impaired the suppressive effects of miR-29b on the malignant phenotypes of gastric cancer cells, suggesting that miR-29b may inhibit gastric cancer growth and metastasis via targeting LASP1. According to these data, miR-29b may be used as a potential therapeutic candidate for gastric cancer.
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