Overexpressed miR-301a promotes cell proliferation and invasion by targeting RUNX3 in gastric cancer

被引:95
|
作者
Wang, Ming [1 ]
Li, Chenglong [1 ]
Yu, Beiqin [1 ]
Su, Liping [1 ]
Li, Jianfang [1 ]
Ju, Jingfang [2 ]
Yu, Yingyan [1 ]
Gu, Qinlong [1 ]
Zhu, Zhenggang [1 ]
Liu, Bingya [1 ]
机构
[1] Shanghai Jiao Tong Univ, Shanghai Key Lab Gastr Neoplasms, Shanghai Inst Digest Surg, Dept Surg,Ruijin Hosp,Sch Med, Shanghai 200025, Peoples R China
[2] SUNY Stony Brook, Med Ctr, Dept Pathol, Stony Brook, NY 11794 USA
基金
中国国家自然科学基金;
关键词
miRNA; Proliferation; Invasion; RUNX3; Gastric cancer; MICRORNA EXPRESSION; EPITHELIAL-CELLS; GENE; DEREGULATION; RNA; ACCUMULATION; SIGNATURE; PROFILES; GROWTH;
D O I
10.1007/s00535-012-0733-6
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
MicroRNAs can promote or suppress the evolution of malignant behaviors by regulating multiple targets. We aimed to determine the expression of miR-301a recently screened in gastric cancer, to investigate the biological effects of miR-301a and to identify the specific miR-301a target gene. Quantitative real-time RT-PCR was used to test miR-301a expression. Functional effects were explored by a water-soluble tetrazolium salt assay, a colony formation assay in soft agar, a migration assay, an invasion assay and cytometry used to determine apoptosis and cell cycle. Nude mice were inoculated subcutaneously by retrovirus-mediated stably expressed SGC-7901 cells. The target gene was determined by bioinformatic algorithms, dual luciferase reporter assay and Western blot. Firstly, we found that miR-301a was significantly upregulated both in cells and tissues of gastric cancer. The expression level of miR-301a was inversely correlated with tumor differentiation of gastric cancer tissues. Secondly, miR-301a promoted cell growth, soft agar clonogenicity, migration, invasion, and decreased cell apoptosis induced by cisplatin in vitro, while blockage of miR-301a reduced the percentage of G2/M phase cells via flow cytometry in gastric cancer cells. Ectopic expression of miR-301a enhanced the subcutaneous tumorigenesis in vivo. Finally, miR-301a directly downregulated RUNX3 expression post-transcriptionally in gastric cancer. Our results demonstrate that miR-301a plays important roles in the development of gastric cancer.
引用
收藏
页码:1023 / 1033
页数:11
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