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MicroRNA-1258 suppresses tumour progression via GRB2/Ras/Erk pathway in non-small-cell lung cancer.


ABSTRACT: OBJECTIVES:Lung cancer is still a disease with high morbidity and mortality in the world. MicroRNAs have been proven to act as an indispensable role in the reuse of multiple solid tumours. Although miR-1258 plays a vital role in suppressing metastasis in breast cancer and gastric cancer, the specific biological function of miR-1258 in non-small-cell lung cancer remains unclear. METHODS:The differential expression of miR-1258 in NSCLC tissues and corresponding paracancerous tissues was detected by qRT-PCR and ISH. Flow cytometry and CCK-8, EdU, tubule formation, and senescence assays were performed, and xenograft models were studied to explore the function of miR-1258. Potential targets of miR-1258 were verified by dual luciferase reporter assay, qRT-PCR, IHC and Western blotting. RESULTS:In vitro and in vivo gain- and loss-of-function assays suggested that miR-1258 inhibits NSCLC cell proliferation and induces senescence and apoptosis. The luciferase reporter assay, IHC and Western blotting analysis showed that GRB2 is one of the direct targets of miR-1258. The GRB2 overexpression plasmid can reverse the functional changes after overexpression of miR-1258. In contrast, miR-1258 inhibitor significantly reversed si-GRB2-induced GRB2 down-regulation. Mechanistically, overexpression of miR-1258 inhibits GRB2 expression and then leads to inactivation of the Ras/Erk oncogenic pathway. CONCLUSIONS:Our results indicate that miR-1258 can suppress NSCLC progression by targeting the GRB2/Ras/Erk pathway, which may lead to different insights into potential biomarkers and novel therapeutic strategies for NSCLC patients.

SUBMITTER: Jiang W 

PROVIDER: S-EPMC6528891 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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MicroRNA-1258 suppresses tumour progression via GRB2/Ras/Erk pathway in non-small-cell lung cancer.

Jiang Wei W   Wei Ke K   Pan Chunfeng C   Li Hong H   Cao Jing J   Han Xu X   Tang Yu Y   Zhu Shichao S   Yuan Weiwei W   He Yaozhou Y   Xia Yang Y   Chen Liang L   Chen Yijiang Y  

Cell proliferation 20180802 6


<h4>Objectives</h4>Lung cancer is still a disease with high morbidity and mortality in the world. MicroRNAs have been proven to act as an indispensable role in the reuse of multiple solid tumours. Although miR-1258 plays a vital role in suppressing metastasis in breast cancer and gastric cancer, the specific biological function of miR-1258 in non-small-cell lung cancer remains unclear.<h4>Methods</h4>The differential expression of miR-1258 in NSCLC tissues and corresponding paracancerous tissues  ...[more]

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