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MiR-124 Inhibits Lung Tumorigenesis Induced by K-ras Mutation and NNK.


ABSTRACT: Dysregulated miRNAs play important role in K-ras mutation or smoking caused lung tumorigenesis. Here, we investigate the role and mechanism of miR-124 in K-ras mutation or smoking-caused lung tumorigenesis and evaluate the therapeutic potential of miR-124 agomiR in K-ras mutation or smoking-caused lung cancer treatment. Our data show that smoking suppresses miR-124 expression, and decreased miR-124 expression is inversely correlated with the p-Akt level and predicts poor overall survival in non-small-cell lung cancer (NSCLC) patients. The overexpression of miR-124 suppressed NSCLC growth by inhibiting the Akt pathway by targeting Akt1 and Akt2. In addition, the systemic delivery of miR-124 agomiR dramatically suppressed tumorigenesis in both NNK-induced lung cancer model and K-rasLA1 transgenic mice by increasing apoptosis and inhibiting cell proliferation. Our findings suggest that smoking inhibits the expression of miR-124, and decreased miR-124 contributes to Akt activation, thereby promoting NSCLC progression. Our findings also represent a novel potential therapeutic strategy for lung cancer.

SUBMITTER: Jin H 

PROVIDER: S-EPMC5633347 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature

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miR-124 Inhibits Lung Tumorigenesis Induced by K-ras Mutation and NNK.

Jin Hua H   Li Qing Q   Cao Fenghao F   Wang Shu-Nan SN   Wang Ren-Tao RT   Wang Yun Y   Tan Qun-You QY   Li Cheng-Run CR   Zou Hua H   Wang Dong D   Xu Cheng-Xiong CX  

Molecular therapy. Nucleic acids 20170915


Dysregulated miRNAs play important role in K-ras mutation or smoking caused lung tumorigenesis. Here, we investigate the role and mechanism of miR-124 in K-ras mutation or smoking-caused lung tumorigenesis and evaluate the therapeutic potential of miR-124 agomiR in K-ras mutation or smoking-caused lung cancer treatment. Our data show that smoking suppresses miR-124 expression, and decreased miR-124 expression is inversely correlated with the p-Akt level and predicts poor overall survival in non-  ...[more]

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