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

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...

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Published in:Heliyon 2020-12, Vol.6 (12), p.e05734-e05734, Article e05734
Main Authors: Mendonça, Daniela Baccelli, Nguyen, Joe Truong, Haidar, Fatima, Fox, Alexandra Lucienne, Ray, Connor, Amatullah, Halimah, Liu, Fei, Kim, Jin Koo, Krebsbach, Paul H.
Format: Article
Language:English
Subjects:
Cancer research
Cell biology
Cell migration
Cell proliferation
Gene expression
Gene regulation
Lung cancer
mEAK-7
MicroRNA-1911-3p
mTOR signaling
Oncology
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Summary: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. MicroRNA-1911-3p; mEAK-7; mTOR signaling; Lung cancer; Cell proliferation; Cell migration; Cell biology; Gene expression; Gene regulation; Cancer research; Oncology.
ISSN:2405-8440
2405-8440
DOI:10.1016/j.heliyon.2020.e05734