MicroRNA-23a/27a/24-2 cluster promotes gastric cancer cell proliferation synergistically

被引:28
作者
Hua, Kate [1 ,2 ]
Chen, Yu-Ting [1 ]
Chen, Chian-Feng [2 ]
Tang, Ya-Syuan [1 ]
Huang, Tzu-Ting [1 ,3 ]
Lin, Yu-Cheng [1 ]
Yeh, Tien-Shun [1 ,3 ,4 ,5 ]
Huang, Kuo-Hung [6 ,7 ]
Lee, Hsin-Chen [1 ]
Hsu, Ming-Ta [2 ,4 ]
Chi, Chin-Wen [1 ,8 ]
Wu, Chew-Wun [6 ]
Lin, Chi-Hung [2 ,9 ,10 ]
Ping, Yueh-Hsin [1 ,2 ,10 ]
机构
[1] Natl Yang Ming Univ, Sch Med, Dept & Inst Pharmacol, 155 Sect,2 Linong St, Taipei 11221, Taiwan
[2] Natl Yang Ming Univ, Sch Med, VYM Genome Res Ctr, Taipei 11221, Taiwan
[3] Natl Yang Ming Univ, Sch Med, Dept Anat & Cell Biol, Taipei, Taiwan
[4] Natl Yang Ming Univ, Inst Biochem & Mol Biol, Taipei 11221, Taiwan
[5] Taipei Med Univ, Coll Med, Grad Inst Med Sci, Taipei 11031, Taiwan
[6] Taipei Vet Gen Hosp, Dept Surg, Taipei, Taiwan
[7] Natl Yang Ming Univ, Sch Med, Inst Clin Med, Taipei, Taiwan
[8] Taipei Vet Gen Hosp, Dept Med Res, Taipei, Taiwan
[9] Inst Microbiol & Immunol, Taipei, Taiwan
[10] Natl Yang Ming Univ, Inst Biophoton, Taipei 11221, Taiwan
关键词
microRNA-23a/27a/24-2; cluster; gastric cancer; suppressor of cytokine-induced signaling 6; TUMOR-SUPPRESSOR; MICRORNAS; EXPRESSION; ADENOCARCINOMA; IDENTIFICATION; APOPTOSIS; MIGRATION; PATTERNS; INVASION; GROWTH;
D O I
10.3892/ol.2018.8924
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Previous studies have indicated that certain microRNAs (miRNAs/miRs) function as either tumor suppressors or oncogenes in human cancer. The present study identified the miR-23a/27a/24-2 cluster, containing miR-23, miR-27a and miR-24, as an oncogene in gastric cancer. The expression of the miR-23a/27a/24-2 cluster was upregulated in clinical gastric cancer tissues. Transfection with inhibitors of miR-23a, miR-27a, or miR-24, either independently or together, repressed in vitro colony formation and in vivo tumor formation. The miR23a/27a/24-2 cluster inhibitors repressed the growth of gastric cancer cells in a synergistic manner. In addition, treatment with lower doses of the miRNA inhibitor mixture induced the formation of apoptotic bodies. According to computational predictions using TargetScan, suppressor of cytokine-induced signaling 6 (SOCS6) was identified as one of the downstream target genes of the miR-23a/27a/24-2 cluster. The expression of SOCS6 was significantly lower in tumor tissues than in matched normal tissues (P<0.01) and was associated with poor survival (P<0.00001). Taken together, these results strongly suggested that the miR-23a/27a/24-2 cluster may mediate the progression of gastric cancer through the suppression of SOCS6 expression. The present study also provides a novel molecular target for the development of an anti-gastric cancer agent.
引用
收藏
页码:2319 / 2325
页数:7
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