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Novel Targets and Biomarkers in Solid Tumors

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Front. Pharmacol. | doi: 10.3389/fphar.2018.01362

MiR-3188 inhibits non-small cell lung cancer cell proliferation through FOXO1-mediated mTOR-p-PI3K/AKT-c-JUN signaling pathway

 Chunyan Wang1, Enqi Liu1, Wen Li1,  Jue Cui1 and  Tongxiang Li1*
  • 1Xuzhou Institute of Technology, China

This study investigated the role of miR-3188 on the proliferation of non-small cell lung cancer cells and its relationship to FOXO1-modulated feedback loop. Two non-small cell lung cancer (NSCLC) cell lines A549 and H1299 were used. RNA silencing was achieved by lentiviral transfection. Cell proliferation was assessed by immunohistochemical staining of Ki67 and PCNA, Edu incorporation and colony formation assay. Western blotting was used to examine expression of FOXO1, mTOR, p-mTOR, CCND1, p21, c-JUN, AKT, pAKT, PI3K, p-PI3K and p27 proteins. It was found that miR-3188 reduced cell proliferation in NSCLC cells. Molecular analyses indicated that the effect of mammalian target of rapamycin (mTOR) was directly mediated by miR-3188, leading to p-PI3K/p-AKT/c-JUN inactivation. The inhibition of this signaling pathway further caused cell-cycle suppression. Moreover, FOXO1 was found to be involved in regulating the interaction of miR-3188 and mTOR through p-PI3K/p-AKT/c-JUN signaling pathway. Taken together, our study demonstrated that miR-3188 interacts with mTOR and FOXO1 to inhibit NSCLC cell proliferation through a mTOR-p-PI3K/AKT-c-JUN signaling pathway. Therefore, miR-3188 might be a potential target for the treatment of NSCLC.

Keywords: miR-3188, NSCLC, proliferation, mTOR, PI3K/AKT, c-jun

Received: 19 Sep 2018; Accepted: 05 Nov 2018.

Edited by:

Dong-Hua Yang, St. John's University, United States

Reviewed by:

Haichang Li, The Ohio State University, United States
QIsi Lu, The Third Affiliated Hospital of Southern Medical University, China  

Copyright: © 2018 Wang, Liu, Li, Cui and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Dr. Tongxiang Li, Xuzhou Institute of Technology, Xuzhou, China, litxresearch@126.com