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Front. Oncol. | doi: 10.3389/fonc.2019.00808

Exogenous let-7a-5p induces A549 lung cancer cell death through BCL2L1-mediated PI3Kγ signaling pathway

 Lin Zhang1*, Shuyin Duan2, Songcheng Yu2, Teng Yuan3 and Sanqiao Yao3, 4
  • 1Weifang Medical University, China
  • 2Zhengzhou University, China
  • 3North China University of Science and Technology, China
  • 4Xinxiang Medical University, China

Elevated expression of let-7a-5p contributes to suppression of lung cancer, in which let-7a-5p, as exosome cargo, can be transported from macrophages to lung cancer cells, yet the role of let-7a-5p remains unclear. Utilizing bioinformatics methods and cellular experiments, this study was designed and conducted to identify let-7a-5p regulatory network in lung cancer. Bioinformatics analysis and Kaplan-Meier survival analysis revealed that let-7a-5p could directly target BCL2L1, and aberrant expression of let-7a-5p affects the survival of lung cancer patients, which was confirmed in A549 lung cancer cells using luciferase reporter assay. Moreover, let-7a-5p inhibited BCL2L1 expression and suppressed lung cancer cell proliferation, migration, and invasion. Functionally, overexpression of let-7a-5p promoted both autophagy and cell death in A549 lung cancer cells through PI3Kγ signaling pathway, whereas the apoptosis and pyroptosis of A549 lung cancer cells were unaffected. Furthermore, aberrant expression of BCL2L1 significantly altered the expression of lung cancer biomarkers such as MYC, EGFR, and Vimentin. To sum up, these data demonstrate that exogenous let-7a-5p induces A549 lung cancer cell death through BCL2L1-mediated PI3Kγ signaling pathway, which may be a useful target for lung cancer treatment.

Keywords: lung cancer, macrophage, exosome, Bcl2l1, Let-7a-5p, Autophagy

Received: 31 Mar 2019; Accepted: 07 Aug 2019.

Edited by:

Saverio Marchi, Marche Polytechnic University, Italy

Reviewed by:

Vassilis G. Gorgoulis, Department of Medicine, School of Health Sciences, National and Kapodistrian University of Athens, Greece
Ying Wang, University of Macau, China  

Copyright: © 2019 Zhang, Duan, Yu, Yuan and Yao. 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: Prof. Lin Zhang, Weifang Medical University, Weifang, 261053, Shandong Province, China, zhanglin8901@163.com