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MicroRNA‐628‐5p inhibits invasion and migration of human pancreatic ductal adenocarcinoma via suppression of the AKT/NF‐kappa B pathway
Author(s) -
Zhou Lin,
Jiao Xiaoxiao,
Peng Xiaoqian,
Yao Xiaomeng,
Liu Lu,
Zhang Lianfeng
Publication year - 2020
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.29468
Subject(s) - microrna , gene knockdown , gene silencing , cancer research , downregulation and upregulation , cell growth , biology , pi3k/akt/mtor pathway , protein kinase b , apoptosis , rna interference , cell culture , signal transduction , microbiology and biotechnology , rna , gene , biochemistry , genetics
The biological function and underlying mechanism of microRNA‐628‐5p (miR‐628‐5p) remains to be clarified in the growth and progression of pancreatic ductal adenocarcinoma (PDAC). Here, the expression levels of miR‐628‐5p in PDAC tissues and cells were detected by quantitative reverse transcriptase polymerase chain reaction and in situ hybridization. The relationship between miR‐628‐5p expression and clinicopathologic characteristics was examined in human PDAC tissue samples. Gain‐ and loss‐of‐function and the putative targets of miR‐628‐5p were evaluated in PDAC cell lines. The upstream and downstream signals of miR‐628‐5p in PDAC were also examined. MiR‐628‐5p was lowly expressed in PDAC tissues and cell lines, and low miR‐628‐5p expression in PDAC tissues was associated with poor clinicopathological characteristics and shorter overall survival. Functionally, restoration of miR‐628‐5p expression decreased PDAC cell proliferation, migration, invasion, and promoted cell apoptosis, whereas miR‐628‐5p silencing abolished these biological behaviors. MiR‐628‐5p was found to target and negatively regulate phospholipid scramblase 1 and insulin receptor substrate 1 expression, which resulted in the inhibition of the AKT/NF‐κB signaling pathway. MYC knockdown led to miR‐628‐5p upregulation, whereas MYC overexpression repressed miR‐628‐5p expression. These findings indicate that miR‐628‐5p functions as a tumor‐suppressive microRNA in PDAC and implicate miR‐628‐5p as a potential therapeutic target for PDAC patients.