MicroRNA-1911-3p targets mEAK-7 to suppress mTOR signaling in human lung cancer cells

Daniela Baccelli Mendonça; Joe Truong Nguyen; Fatima Haidar; Alexandra Lucienne Fox; Connor Ray; Halimah Amatullah; Fei Liu; Jin Koo Kim; Paul H Krebsbach

doi:10.1016/j.heliyon.2020.e05734

MicroRNA-1911-3p targets mEAK-7 to suppress mTOR signaling in human lung cancer cells

Heliyon. 2020 Dec 19;6(12):e05734. doi: 10.1016/j.heliyon.2020.e05734. eCollection 2020 Dec.

Authors

Daniela Baccelli Mendonça^{1

2}, Joe Truong Nguyen^{1

2}, Fatima Haidar^{1

2}, Alexandra Lucienne Fox^{1

2}, Connor Ray^{1

2}, Halimah Amatullah^{1

2}, Fei Liu¹, Jin Koo Kim³, Paul H Krebsbach³

Affiliations

¹ Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48105, USA.
² Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48105, USA.
³ Section of Periodontics, University of California, Los Angeles, School of Dentistry, Los Angeles, CA, 90095, USA.

Abstract

Regulation of mTOR signaling depends on an intricate interplay of post-translational protein modification. Recently, mEAK-7 (mTOR associated protein, eak-7 homolog) was identified as a positive activator of mTOR signaling via an alternative mTOR complex. However, the upstream regulation of mEAK-7 in human cells is not known. Because microRNAs are capable of modulating protein translation of RNA in eukaryotes, we conducted a bioinformatic search for relevant mEAK-7 targeting microRNAs using the Exiqon miRSearch V3.0 algorithm. Based on the score obtained through miRSearch V3.0, the top predicted miRNA (miR-1911-3p) was studied. miR-1911-3p mimics decreased protein levels of both mEAK-7 and mTORC1 downstream effectors p-S6 and p-4E-BP1 in non-small cell lung carcinoma (NSCLC) cell lines H1975 and H1299. miR-1911-3p levels and MEAK7 mRNA/mEAK-7/mTOR signaling levels were negatively correlated between normal lung and NSCLC cells. miR-1911-3p directly interacted with MEAK7 mRNA at the 3'-UTR to negatively regulate mEAK-7 and significantly decreased mTOR localization to the lysosome. Furthermore, miR-1911-3p significantly decreased cell proliferation and migration in both H1975 and H1299 cells. Thus, miR-1911-3p functions as a suppressor of mTOR signaling through the regulation of MEAK7 mRNA translation in human cancer cells.

Keywords: Cancer research; Cell biology; Cell migration; Cell proliferation; Gene expression; Gene regulation; Lung cancer; MicroRNA-1911-3p; Oncology; mEAK-7; mTOR signaling.