Role of NADH Dehydrogenase (Ubiquinone) 1 Alpha Subcomplex 4-Like 2 in Clear Cell Renal Cell Carcinoma

Clinical Cancer Research : an Official Journal of the American Association for Cancer Research
Denise R MintonLorraine J Gudas

Abstract

We delineated the functions of the hypoxia-inducible factor-1α (HIF1α) target NADH dehydrogenase (ubiquinone) 1 alpha subcomplex 4-like 2 (NDUFA4L2) in clear cell renal cell carcinoma (ccRCC) and characterized NDUFA4L2 as a novel molecular target for ccRCC treatment. We evaluated normal kidney and ccRCC patient microarray and RNAseq data from Oncomine and The Cancer Genome Atlas for NDUFA4L2 mRNA levels and the clinical implications of high NDUFA4L2 expression. In addition, we examined normal kidney and ccRCC patient tissue samples, human ccRCC cell lines, and murine models of ccRCC for NDUFA4L2 mRNA and protein expression. Utilizing short hairpin RNA, we performed NDUFA4L2 knockdown experiments and analyzed the proliferation, clonogenicity, metabolite levels, cell structure, and autophagy in ccRCC cell lines in culture. We found that NDUFA4L2 mRNA and protein are highly expressed in ccRCC samples but undetectable in normal kidney tissue samples, and that NDUFA4L2 mRNA expression correlates with tumor stage and lower overall survival. In addition, we demonstrated that NDUFA4L2 is an HIF1α target in ccRCC and that NDUFA4L2 knockdown has a profound antiproliferative effect, alters metabolic pathways, and causes major stress in cu...Continue Reading

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Citations

Apr 7, 2020·The Journal of Experimental Medicine·Anirban KunduSunil Sudarshan
Oct 5, 2017·Cancer Immunology, Immunotherapy : CII·Atsunari KawashimaHisashi Wada
Jun 9, 2017·Oxidative Medicine and Cellular Longevity·Christopher A SinklerMaik Hüttemann
May 3, 2019·BMC Bioinformatics·Chen WangXiaodong Cai
Dec 20, 2020·Journal of Cellular and Molecular Medicine·Yun LiuZengxian Sun
Jan 9, 2021·Frontiers in Oncology·Jill AlldredgeFarah Rahmatpanah
Mar 28, 2021·Experimental Cell Research·Yi WeiZongpei Jiang
May 29, 2021·Frontiers in Oncology·Natalya ApanovichAlexander Karpukhin
Nov 2, 2021·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Zhengye LiuJohanna T Lanner

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