A microRNA-mediated decrease in eukaryotic initiation factor 2α promotes cell survival during PS-341 treatment.

Scientific Reports
Lili JiangJinbao Liu

Abstract

MicroRNAs (miRs) play pivotal roles in carcinogenesis and endoplasmic reticulum (ER) that performs the folding, modification and trafficking of proteins targeted to the secretory pathway. Cancer cells often endure ER stress during tumor progression but use the adaptive ER stress response to gain survival advantage. Here we report: (i) A group of miRs, including miR-30b-5p and miR-30c-5p, are upregulated by proteasome inhibitor PS-341 treatment, in HepG2 and MDA-MB-453 cells. (ii) Two representative PS-341-induced miRs: miR-30b-5p and miR-30c-5p are found to promote cell proliferation and anti-apoptosis in both tumor cells. (iii) eIF2α is confirmed as the congenerous target of miR-30b-5p and miR-30c-5p, essential to the anti-apoptotic function of these miRs. (iv) Upregulation of miR-30b-5p or miR-30c-5p, which occurs latter than the increase of phosphorylated eIF2α (p-eIF2α) in the cell under ER stress, suppresses the p-eIF2α/ATF4/CHOP pro-apoptotic pathway. (v) Inhibition of the miR-30b-5p or miR-30c-5p sensitizes the cancer cells to the cytotoxicity of proteasome inhibition. In conclusion, we unravels a new miRs-based mechanism that helps maintain intracellular proteostasis and promote cell survival during ER stress through up...Continue Reading

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Citations

Jun 24, 2017·American Journal of Physiology. Cell Physiology·Mari McMahonEric Chevet
Dec 4, 2019·The Journal of Biological Chemistry·Nobuhiko HiramatsuJonathan H Lin
Jan 1, 2020·Journal of Translational Medicine·Helena Estevão-PereiraCarmen Jerónimo
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Feb 2, 2021·The Journal of Biological Chemistry·Nobuhiko HiramatsuJonathan H Lin
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Aug 10, 2018·Science Translational Medicine·Mónica TramullasMaría A Hurlé

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Methods Mentioned

BETA
protein folding
PCR
flow cytometry
antisense oligonucleotide
protein assay
transfection

Software Mentioned

ModFit LT
TargetScan

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