MicroRNA-421 regulated by HIF-1α promotes metastasis, inhibits apoptosis, and induces cisplatin resistance by targeting E-cadherin and caspase-3 in gastric cancer

被引：102

作者：

Ge, Xiaoxiao ^{[1
,2
]}

Liu, Xinyang ^{[3
,4
]}

Lin, Fengjuan ^{[1
,2
]}

Li, Peng ^{[4
]}

Liu, Kaiyi ^{[1
,2
]}

Geng, Ruixuan ^{[5
]}

Dai, Congqi ^{[1
,2
]}

Lin, Ying ^{[1
,2
]}

Tang, Wenbo ^{[1
,2
]}

Wu, Zheng ^{[1
,2
]}

Chang, Jinjia ^{[1
,2
]}

Lu, Jianwei ^{[6
,7
]}

Li, Jin ^{[1
,2
]}

机构：

[1] Fudan Univ, Shanghai Canc Ctr, Dept Med Oncol, Shanghai 200000, Peoples R China

[2] Fudan Univ, Shanghai Med Coll, Dept Oncol, Shanghai 200000, Peoples R China

[3] Fudan Univ, Shanghai Med Coll, Shanghai 200000, Peoples R China

[4] Harvard Univ, TH Chan Sch Publ Hlth, Boston, MA 02115 USA

[5] Peking Union Med Coll Hosp, Int Med Serv, Beijing 100000, Peoples R China

[6] Tongji Univ, Adv Inst Translat Med, Shanghai 200073, Peoples R China

[7] Tongji Univ, Sch Software Engn, Shanghai 200073, Peoples R China

来源：

ONCOTARGET | 2016年 / 7卷 / 17期

关键词：

gastric cancer; miR-421; HIF-1; alpha; cisplatin resistance; epithelial-mesenchymal transition; EPITHELIAL-MESENCHYMAL TRANSITION; HYPOXIA-INDUCIBLE FACTORS; HUMAN BLADDER-CANCER; TUMOR-SUPPRESSOR; DOWN-REGULATION; DRUG-RESISTANCE; CELL INVASION; PROLIFERATION; EXPRESSION; CARCINOMA;

D O I：

10.18632/oncotarget.8228

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Hypoxia and dysregulation of microRNAs (miRNAs) have been identified as crucial factors in carcinogenesis. However, the potential mechanisms of HIF-1 alpha and miR-421 in gastric cancer have not been well elucidated. In this study, we found that miR-421 was up-regulated by HIF-1 alpha. Overexpression of miR-421 promoted metastasis, inhibited apoptosis, and induced cisplatin resistance in gastric cancer in vivo and in vitro. E-cadherin and caspase-3 were identified as targets of miR-421. Besides, relative mRNA expression of miR-421 was significantly increased in gastric cancer tumor tissues compared with non-tumor tissues in a cohort of gastric cancer specimens (n=107). The expression of miR-421 was higher in advanced gastric cancers compared with localized ones. Moreover, Kaplan-Meier analysis illustrated that those patients with low levels of miR-421 had a significant longer overall survival (p = 0.006) and time to relapse (p = 0.007). Therefore, miR-421 could serve as an important prognostic marker and a potential molecular target for therapy in gastric cancer.

引用

页码：24466 / 24482

页数：17

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