DNMT3A-mediated down-regulation of microRNA-105 promotes gastric cancer cell proliferation

G.-Q. Zhou, F. Han, Z.-L. Shi, L. Yu, X.-F. Li, C. Yu, C.-L. Shen, D.-W. Wan, X.-G. Zhu, R. Li, S.-B. He

Department of Gastrointestinal Surgery, Changshu No. 2 Hospital, Suzhou, Jiangsu Province, China. captain_hsb@163.com

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• Oncology

OBJECTIVE: It has been well-established that microRNAs (miRNAs), a class of short non-coding RNA molecules, play an important role in the development of gastric cancer. In the present study, we focused on miR-105, a novel miRNA not previously linked to gastric cancer.

PATIENTS AND METHODS: 36 paired surgically resected gastric cancer tissues and matched adjacent normal tissues were used to detect the expression of miR-105. AGS cells were used to overexpress or silence of miR-105 and to determine its effect on several tumorigenic properties. A cell proliferation enzyme-linked immunosorbent assay was used to analyze the incorporation of BrdU during DNA synthesis of AGS cells. Total cDNA from AGS cells was used to amplify the 3’-UTR of YY1 by PCR and luciferase activity was determined using the Dual-Luciferase Reporter Assay System

RESULTS: We found that expression of miR-105 was reduced in gastric cancer tissues, compared with adjacent normal tissues, due to hypermethylation at its promoter region. Overexpression of miR-105 suppressed, whereas its inhibition promoted cell viability and proliferation. We further identified Yin Yang 1 (YY1) as a direct target of miR-105, by which miR-105 exerted its anti-proliferative role. Moreover, we found that DNMT3A was responsible for the down-regulation of miR-105 in gastric cancer cells.

CONCLUSIONS: Our data demonstrate that miR-105 inhibits gastric cancer cell proliferation and progression, which might provide a therapeutical target for cancer therapy.

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