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Figure S2 from miR-217 Regulates Normal and Tumor Cell Fate Following Induction of Endoplasmic Reticulum Stress

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posted on 2024-04-02, 07:22 authored by Neekkan Dey, Costas Koumenis, Davide Ruggero, Serge Y. Fuchs, J. Alan Diehl

S2. AGS cells infected with either control or miR-217 were exposed to Tg (300nM) for 0, 2, 5 and 8 hours. Cells were exposed to actinomycin D (2 ᵰ7g/ml) where indicated after 5 hours of Tg treatment (and kept throughout the indicated timepoint). MiR-211 and miR-217 expression levels were quantified by qPCR. Error bars represent standard deviation for three independent experiments.

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Office of Extramural Research, National Institutes of Health (OER)

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ARTICLE ABSTRACT

Rapidly proliferating cancer cells require a microenvironment where essential metabolic nutrients like glucose, oxygen, and growth factors become scarce as the tumor volume surpasses the established vascular capacity of the tissue. Limits in nutrient availability typically trigger growth arrest and/or apoptosis to prevent cellular expansion. However, tumor cells frequently co-opt cellular survival pathways thereby favoring cell survival under this environmental stress. The unfolded protein response (UPR) pathway is typically engaged by tumor cells to favor adaptation to stress. PERK, an endoplasmic reticulum (ER) protein kinase and UPR effector is activated in tumor cells and contributes tumor cell adaptation by limiting protein translation and balancing redox stress. PERK also induces miRNAs that contribute to tumor adaptation. miR-211 and miR-216b were previously identified as PERK-ATF4–regulated miRNAs that regulate cell survival. We have identified another PERK-responsive miRNA, miR-217, with increased expression under prolonged ER stress. Key targets of miR-217 are identified as TRPM1, the host gene for miR-211 and EZH2. Evidence is provided that miR-217 expression is essential for the rapid loss of miR-211 in prolonged ER stress and provides a functional link for determining whether cells adapt to stress or commit to apoptosis. PERK-dependent induction of miR-217 limits accumulation and function of the prosurvival miRNA, miR-211, to establish cell fate and promote cell commitment to apoptosis.

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