miRNA-101 Suppresses Epithelial-to-mesenchymal Transition by Targeting HMGA2 in Pancreatic Cancer Cells

Author(s): Wenli Jiang, Wen Gu, Ronglin Qiu, Songbing He, Chenglong Shen, Yaohao Wu, Jie Zhang, Jiajia Zhou, Yixing Guo, Daiwei Wan, Zhixi Li, Jiemin Deng, Lexiang Zeng, Jin Tang, Jin Zhou, Qiaoming Zhi, Xiaogeng Deng.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 16 , Issue 4 , 2016

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Abstract:

miR-101 is an outstanding tumor suppressor in various cancers, while its role in pancreatic cancer (PC) is still unknown. The aim of this study was to investigate the role of miR-101 in epithelial-to-mesenchymal transition (EMT) and its clinical relevance in PC. Our data showed that the miR-101 expression was significantly decreased in human PC tissues, compared to non-tumor counterparts (p<0.05), which was reversely correlated to clinical characteristics, including lymph node metastasis, more venous infiltration, higher expression of CA19-9 and TNM stage (p<0.05). Low miR-101 expression was also confirmed to be associated with a poorer overall survival rate in PC patients (p<0.05). We identified high-mobility group AT-hook 2 (HMGA2) gene as a putative target of miR-101 in PC by bioinformatics analysis, dual luciferase activity and western blot assay, and found that miR-101 could specifically target the HMGA2 3’-untranslated region (3’-UTR) (p<0.05). Knockdown of HMGA2 reversed EMT resembling that of miR-101 over-expression. An inverse correlation between miR-101 and HMGA2 was observed in patients with PC (p<0.05). Taken together, our findings speculated that miR-101 might act as an inhibiting factor in EMT process in PC and up-regulation of miR-101 might be considered as a potentially key molecular treatment strategy for PC patients.

Keywords: Epithelial-to-mesenchymal transition, HMGA2, miR-101, pancreatic cancer.

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Article Details

VOLUME: 16
ISSUE: 4
Year: 2016
Page: [432 - 439]
Pages: 8
DOI: 10.2174/1871520615666150507122142
Price: $58

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