miR-93 functions as an oncomiR for the downregulation of PDCD4 in gastric carcinoma

被引:48
作者
Liang, Hongwei [1 ]
Wang, Feng [2 ,3 ]
Chu, Danping [1 ]
Zhang, Weijie [2 ,3 ]
Liao, Zhicong [3 ,4 ]
Fu, Zheng [1 ]
Yan, Xin [3 ,5 ]
Zhu, Hao [3 ,6 ]
Guo, Wen [7 ]
Zhang, Yujing [1 ]
Guan, Wenxian [2 ,3 ]
Chen, Xi [1 ]
机构
[1] Nanjing Univ, NJU Adv Inst Life Sci, State Key Lab Pharmaceut Biotechnol,Sch Life Sci, Jiangsu Engn Res Ctr MicroRNA Biol & Biotechnol, Nanjing 210093, Jiangsu, Peoples R China
[2] Nanjing Univ, Sch Med, Dept Gen Surg, Affiliated Drum Tower Hosp, Nanjing 210008, Jiangsu, Peoples R China
[3] Nanjing Multictr Biobank, Nanjing 210008, Jiangsu, Peoples R China
[4] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Dept Cardiothorac Surg, Nanjing 210008, Jiangsu, Peoples R China
[5] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Dept Resp Med, Nanjing 210008, Jiangsu, Peoples R China
[6] Nanjing Univ, Sch Med, Affiliated Drum Tower Hosp, Dept Gastroenterol, Nanjing 210008, Jiangsu, Peoples R China
[7] Nanjing Municipal Hosp Govt Org, Dept Endocrinol, Nanjing 210018, Jiangsu, Peoples R China
基金
中国国家自然科学基金;
关键词
CELL-DEATH; 4; MICRORNA-93; EXPRESSION; APOPTOSIS; PATHWAY; INVOLVEMENT; CLUSTER; TARGET;
D O I
10.1038/srep23772
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Programmed cell death 4 (PDCD4), as a tumor suppressor gene, is frequently reduced in a variety of tumors, including gastric cancer. Previous findings have indicated that PDCD4 participates in tumorigenesis through the regulation of apoptosis, but the molecular basis of this process has not been fully elucidated, and no studies have shown the upstream regulation of this gene in gastric cancer. In this study, we used bioinformatics analysis to search for miRNAs that could potentially target PDCD4 and identified miR-93 as a candidate. Moreover, we observed the inverse correlation between miR-93 and PDCD4 protein levels, but not mRNA levels, in human gastric cancer tissues. We further experimentally validated PDCD4 as the direct target of miR-93 by evaluating PDCD4 expression in gastric cancer cells after the overexpression or knockdown of miR-93. Additionally, the biological consequences of targeting PDCD4 through miR-93 were examined using cell apoptosis assays in vitro. We demonstrated that the repression of PDCD4 through miR-93 suppressed the apoptosis of gastric cancer cells. Finally, we revealed that miR-93 promoted the development of gastric tumor growth in xenograft mice by negatively regulating PDCD4. Taken together, the findings of the present study indicated the oncogenic role of miR-93 in gastric cancer tumorigenesis through targeting PDCD4, particularly in apoptosis.
引用
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页数:11
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