GRIM-19 inhibition induced autophagy through activation of ERK and HIF-1α not STAT3 in Hela cells

Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine
Xin YueXuelian He

Abstract

Gene associated with retinoid-interferon-induced mortality (GRIM-19), an important subunit of mitochondrial complex I, has been identified as a tumor suppressor, and its reduced expression has been reported to be associated with tumorigenesis and metastasis. Autophagy has been proposed as a protective mechanism for cell survival under various stresses, including chemotherapy. However, it remains unknown whether GRIM-19 is linked to autophagy and chemotherapy resistance. Here, we showed that suppression of GRIM-19 by shRNA enhanced cell-type-dependent autophagy by activating extracellular regulated protein kinase (ERK) and hypoxia inducible factor-1a (HIF-1a) in a reactive oxygen species (ROS)-mediated manner, and thereby conferred resistance to paclitaxel. Besides, the antioxidant N-acetyl-L-cysteine (NAC) and autophagy inhibitor 3-MA could in part overcome this resistance. We also found that GRIM-19 expression was significantly correlated with clinical stage and grade in patients with cervical cancers. Taken together, our results indicated that GRIM-19 inhibition induced autophagy and chemotherapy resistance, which could affect prognosis of cervical cancers. Our study has identified new function of GRIM-19 and its underlying m...Continue Reading

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Citations

Mar 5, 2017·Redox Biology·Dominik C Fuhrmann, Bernhard Brüne
Oct 17, 2018·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ana García Del RíoMaría Simarro
Jan 16, 2020·Biomolecules·Petr JežekLydie Plecitá-Hlavatá
Mar 17, 2018·Experimental and Therapeutic Medicine·Huan GaoYan-Qing Song
Jul 31, 2021·Biomedicine & Pharmacotherapy = Biomédecine & Pharmacothérapie·Fan BieMin Lan

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