Jiang, Wei, Wei, Ke, Pan, Chunfeng, Li, Hong, Cao, Jing, Han, Xu, Tang, Yu, Zhu, Shichao, Yuan, Weiwei, He, Yaozhou, Xia, Yang, Chen, Liang, and Chen, Yijiang
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. [ABSTRACT FROM AUTHOR]