MicroRNA-634 functions as a tumor suppressor in pancreatic cancer via directly targeting heat shock-related 70-kDa protein 2

MicroRNA-634 通过直接靶向热休克相关 70 kDa 蛋白 2 在胰腺癌中发挥肿瘤抑制作用

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作者:Duanrui Chen, Xinglong Wu, Jianwen Zhao, Xiangwen Zhao

Abstract

Pancreatic cancer (PC) is one of the most malignant types of human cancer and has an extremely poor prognosis. MicroRNAs (miRs) reportedly serve a critical role in pancreatic ductal adenocarcinoma (PDAC) progression. Understanding the expression patterns and functions of miRs may provide strategies for the diagnosis and treatment of patients with PC. In particular, miR-634 is attracting interest due to its critical role in regulating the biology of some types of cancer. However, the expression patterns, biological function and molecular mechanism of miR-634 in PC remain unknown. In the present study, miR-634 expression levels in PC tissues and cell lines were significantly downregulated. Notably, the ectopic overexpression of miR-634 in PC cells inhibited tumor progression, whereas miR-634 silencing reversed these effects. Furthermore, reverse transcription-quantitative polymerase chain reaction, western blot analysis and the dual-luciferase assay revealed that miR-634 regulated heat shock-related 70 kDa protein 2 (HSPA2) by directly binding to its 3-untranslated region. In clinical samples of PC, miR-634 was inversely correlated with HSPA2, which was upregulated in PC. In the rescue experiment, HSPA2 overexpression partially abrogated the effects of miR-634 mimicry on biological function. In conclusion, miR-634 functioned as a tumor suppressor in regulating PC progression by targeting HSPA2 and may therefore be a novel potential therapeutic target for PC.

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