miR-125b-5p functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma.

miR-125b-5p functions as a tumor suppressor gene partially by regulating HMGA2 in esophageal squamous cell carcinoma.
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miR-125b-5p 在食管鳞状细胞癌中部分通过调节 HMGA2 发挥抑癌基因的作用。

DOI:
10.1371/journal.pone.0185636
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发表时间:
2017
期刊:
影响因子:
3.7
通讯作者:
Shi ZZ
Shi ZZ
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Mei LL;Wang WJ;Qiu YT;Xie XF;Bai J;Shi ZZ

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MicroRNAs (miRNAs) play important roles in the progression of human cancer including esophageal squamous cell carcinoma (ESCC). Although previous reports showed that miR-125b-5p was down-regulated in ESCC, the roles and mechanisms of loss of function of miR-125b-5p in ESCC were still unknown. Using microRNA microarray and GEO datasets, we found and confirmed that miR-125b-5p was down-regulated in ESCC tissues. In-vitro assays showed that ectopic miR-125b-5p expression repressed cell proliferation, migration and invasion, and induced cell senescence. We also found that miR-125b-5p reduced the expressions of cell cycle regulatory genes including CCNA2, CCND1 and CCNE1, and regulated the markers of epithelial to mesenchymal transition (EMT) including E-cadherin, N-cadherin and EMT associated transcription factor Slug, and also decreased the MMPs including MMP2, MMP7 and MMP13. Furthermore, the candidate target gene HMGA2 was negatively regulated by miR-125b-5p both in mRNA and protein levels. Importantly, knockdown of HMGA2 partially phenocopied the effects of miR-125b-5p overexpression on cell cycle regulators and EMT markers. In conclusion, our results suggested that overexpression of miR-125b-5p inhibited cell proliferation, migration and invasion partially by down-regulating HMGA2 in ESCC.
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