Open AccessMicro RNA ‐1258 suppresses tumour progression via GRB 2/Ras/Erk pathway in non‐small‐cell lung cancer
Author(s) -
Jiang Wei,
Wei Ke,
Pan Chunfeng,
Li Hong,
Cao Jing,
Han Xu,
Tang Yu,
Zhu Shichao,
Yuan Weiwei,
He Yaozhou,
Xia Yang,
Chen Liang,
Chen Yijiang
Publication year - 2018
Publication title -
cell proliferation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.647
H-Index - 74
eISSN - 1365-2184
pISSN - 0960-7722
DOI - 10.1111/cpr.12502
Subject(s) - cancer research , flow cytometry , mapk/erk pathway , blot , cancer , in vivo , biology , cell growth , metastasis , lung cancer , signal transduction , immunology , medicine , microbiology and biotechnology , pathology , gene , genetics , biochemistry
Objectives Lung cancer is still a disease with high morbidity and mortality in the world. Micro RNA s 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 GRB 2 is one of the direct targets of miR‐1258. The GRB 2 overexpression plasmid can reverse the functional changes after overexpression of miR‐1258. In contrast, miR‐1258 inhibitor significantly reversed si‐ GRB 2‐induced GRB 2 down‐regulation. Mechanistically, overexpression of miR‐1258 inhibits GRB 2 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 GRB 2/Ras/Erk pathway, which may lead to different insights into potential biomarkers and novel therapeutic strategies for NSCLC patients.