Elevated PAF1-RAD52 axis confers chemoresistance to human cancers.

Autor:	Rauth S; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Ganguly K; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Atri P; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Parte S; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Nimmakayala RK; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Varadharaj V; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Nallasamy P; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Vengoji R; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Ogunleye AO; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Lakshmanan I; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Chirravuri R; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Bessho M; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Cox JL; Department of Pathology and Microbiology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Foster JM; Department of Surgery, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Talmon GA; Department of Pathology and Microbiology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Bessho T; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Ganti AK; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA; Division of Oncology-Hematology, Department of Internal Medicine, VA Nebraska Western Iowa Health Care System, University of Nebraska Medical Center, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center at Omaha, Omaha, NE, USA., Batra SK; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center at Omaha, Omaha, NE, USA. Electronic address: sbatra@unmc.edu., Ponnusamy MP; Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center at Omaha, Omaha, NE, USA; Fred and Pamela Buffett Cancer Center, Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center at Omaha, Omaha, NE, USA. Electronic address: mpalanim@unmc.edu.
Jazyk:	angličtina
Zdroj:	Cell reports [Cell Rep] 2023 Feb 28; Vol. 42 (2), pp. 112043. Date of Electronic Publication: 2023 Jan 28.
DOI:	10.1016/j.celrep.2023.112043
Abstrakt:	Cisplatin- and gemcitabine-based chemotherapeutics represent a mainstay of cancer therapy for most solid tumors; however, resistance limits their curative potential. Here, we identify RNA polymerase II-associated factor 1 (PAF1) as a common driver of cisplatin and gemcitabine resistance in human cancers (ovarian, lung, and pancreas). Mechanistically, cisplatin- and gemcitabine-resistant cells show enhanced DNA repair, which is inhibited by PAF1 silencing. We demonstrate an increased interaction of PAF1 with RAD52 in resistant cells. Targeting the PAF1 and RAD52 axis combined with cisplatin or gemcitabine strongly diminishes the survival potential of resistant cells. Overall, this study shows clinical evidence that the expression of PAF1 contributes to chemotherapy resistance and worse clinical outcome for lethal cancers. Competing Interests: Declaration of interests S.K.B. is one of the co-founders of Sanguine Diagnostics and Therapeutics, Inc. The other authors declare no competing interests. (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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