Open AccessMiR‐138 inhibits cell proliferation and reverses epithelial‐mesenchymal transition in non‐small cell lung cancer cells by targeting GIT 1 and SEMA 4C
Author(s) -
Li Jiefang,
Wang Qinrong,
Wen Ruiling,
Liang Jieman,
Zhong Xiaoling,
Yang Wei,
Su Dongxiang,
Tang Jun
Publication year - 2015
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12666
Subject(s) - ectopic expression , cancer research , epithelial–mesenchymal transition , gene knockdown , cell growth , semaphorin , biology , microrna , small hairpin rna , lung cancer , cell culture , cancer , metastasis , receptor , medicine , gene , genetics
Non‐small‐cell lung cancer ( NSCLC ) is one of the most common and lethal malignant tumours worldwide with a poor 5‐year survival rate. Recent studies indicated that mi RNA s have been involved in the tumorigenic driver pathways in NSCLC , but the relevant molecular mechanisms are not well‐understood. In this study, we investigated the biological functions and molecular mechanisms of miR‐138 in human NSCLC . The effects of miR‐138 on the NSCLC cell growth and epithelial‐mesenchymal transition ( EMT ) were first examined. Then the targeting connections of miR‐138 with G‐protein‐coupled receptor kinase‐interacting protein 1 ( GIT 1) and semaphorin 4C ( SEMA 4C) were confirmed by dual luciferase reporter assays. Finally, the effects of GIT 1 and SEMA 4C on the NSCLC cell growth and EMT were investigated respectively. We found that the ectopic expression of miR‐138 resulted in a significant inhibition of NSCLC growth and reversion of EMT . GIT 1 and SEMA 4C were identified as two novel targets of miR‐138. Furthermore, GIT 1 and SEMA 4C knockdown inhibited the cell growth and reversed EMT , just like the effects of miR‐138 overexpression on NSCLC cells, whereas ectopic expression of GIT 1 and SEMA 4C partly rescued the suppressive effects of miR‐138 in NSCLC cells. These data represent a crucial step towards the understanding of the novel roles and molecular mechanism of miR‐138, GIT 1 and SEMA 4C in NSCLC progression, which may provide some new targets or prognostic biomarkers for NSCLC treatment, thus having implications in translational oncology.