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

Heliyon (Dec 2020)

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

Affiliations

Daniela Baccelli Mendonça: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48105, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48105, USA
Joe Truong Nguyen: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48105, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48105, USA
Fatima Haidar: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48105, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48105, USA
Alexandra Lucienne Fox: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48105, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48105, USA
Connor Ray: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48105, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48105, USA
Halimah Amatullah: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48105, USA; Biointerfaces Institute, University of Michigan, Ann Arbor, MI, 48105, USA
Fei Liu: Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI, 48105, USA
Jin Koo Kim: Section of Periodontics, University of California, Los Angeles, School of Dentistry, Los Angeles, CA, 90095, USA
Paul H. Krebsbach: Section of Periodontics, University of California, Los Angeles, School of Dentistry, Los Angeles, CA, 90095, USA; Corresponding author.

Journal volume & issue: Vol. 6, no. 12
p. e05734

Abstract

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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.

Published in Heliyon

ISSN: 2405-8440 (Online)
Publisher: Elsevier
Country of publisher: United Kingdom
LCC subjects: Science: Science (General); Social Sciences: Social sciences (General)
Website: https://www.cell.com/heliyon/home

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