{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T15:41:31Z","timestamp":1787586091493,"version":"build-2736575974"},"reference-count":35,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T00:00:00Z","timestamp":1586131200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100010408","name":"Polpharma Scientific Foundation","doi-asserted-by":"publisher","award":["5\/XVII\/18"],"award-info":[{"award-number":["5\/XVII\/18"]}],"id":[{"id":"10.13039\/501100010408","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["IUBMB Life"],"published-print":{"date-parts":[[2020,6]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Renal cell carcinoma (RCC) represents around 2\u20133% of all malignancies diagnosed in adult patients. Most frequent (around 70\u201380% cases) and the most aggressive subtype is clear cell RCC (ccRCC). Mutations in <jats:italic>VHL<\/jats:italic> (von Hippel Lindau) gene, characteristic for this cancer type, lead to altered activity of the trimeric VBC (pVHL\u2010elongin B\u2010C) complex and consequently to HIF\u20101\u03b1 stabilization. In this study, we present results of exhaustive investigation of HIF\u20101\u03b1 alternative transcript variants abundance in A498, CAKI\u20101, and 786\u2010O ccRCC cell lines. We proved the existence of truncated HIF\u20101\u03b1 protein form (HIF1A\u2206\u20106) in A498 and <jats:italic>HIF1A<\/jats:italic> gene rearrangements in 786\u2010O cell lines. Subsequently, we found that HIF1A\u22062\u20106 was more stable than the full\u2010length HIF\u20101\u03b1. Moreover, the shorter HIF\u20101\u03b1 was insensitive for hypoxia and was overaccumulated after proteasome inhibitor treatment indicative of potential diversified roles of full\u2010length and truncated HIF\u20101\u03b1 forms in the cell. We also showed that A498, CAKI\u20101, and 786\u2010O exhibit differential expression of various regulatory genes involved in the control of metabolic processes, that is, glucose and lipid metabolism, and encoding subunits of such machineries like SWI\/SNF chromatin remodeling complex. Furthermore, these cell lines exhibited differential responses to axitinib, everolimus, and sunitinib\u2014anticancer drugs\u2014in normoxia and hypoxia as well as various alterations in metabolism\u2010related regulatory processes. Finally, we have shown that overexpression of truncated HIF1A\u22062\u20106 form may affect the protein level of endogenous full\u2010length HIF\u20101\u03b1 protein. Thus, our study proves an important role of HIF\u20101\u03b1 in the ccRCC development.<\/jats:p>","DOI":"10.1002\/iub.2281","type":"journal-article","created":{"date-parts":[[2020,4,6]],"date-time":"2020-04-06T15:12:21Z","timestamp":1586185941000},"page":"1220-1232","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Various forms of <scp>HIF<\/scp>\u20101\u03b1 protein characterize the clear cell renal cell carcinoma cell lines"],"prefix":"10.1002","volume":"72","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7551-2700","authenticated-orcid":false,"given":"Monika","family":"Swiatek","sequence":"first","affiliation":[{"name":"Department of Molecular and Translational Oncology Maria Sklodowska\u2010Curie National Research Institute of Oncology  Warsaw 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