Kinome-wide CRISPR-Cas9 screens revealed EXOSC10 as a positive regulator of TGF-β signaling

The TGF-β signaling pathway is closely associated with human health and disease, and the systematic identification of factors involved in the TGF-β signaling pathway significantly contributes to the understanding and treatment of various diseases. Through kinome-wide CRISPR screen, we identified 13...

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Main Authors: Dingding Wang, Xinhao Zhang, Jianxun Guo, Weijia Liu, Yanchi Zhou, Renxian Wang
Format: Article
Language:English
Published: Elsevier 2024-12-01
Series:Biochemistry and Biophysics Reports
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Online Access:http://www.sciencedirect.com/science/article/pii/S2405580824002280
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author Dingding Wang
Xinhao Zhang
Jianxun Guo
Weijia Liu
Yanchi Zhou
Renxian Wang
author_facet Dingding Wang
Xinhao Zhang
Jianxun Guo
Weijia Liu
Yanchi Zhou
Renxian Wang
author_sort Dingding Wang
collection DOAJ
description The TGF-β signaling pathway is closely associated with human health and disease, and the systematic identification of factors involved in the TGF-β signaling pathway significantly contributes to the understanding and treatment of various diseases. Through kinome-wide CRISPR screen, we identified 13 candidate regulatory targets. Notably, the well-known hallmark genes TGFBR1 and TGFBR2 emerged as the top two candidate targets. OXSR1 and EXOSC10 were ranked third and fourth as positive candidate targets, respectively, with EXOSC10 being a novel discovery. Importantly, our findings revealed the down-regulation of OXSR1 and EXOSC10 using CRISPR knockout and RNAi technology effectively suppressed the TGF-β signaling pathway in HeLa and HaCaT cells, providing new insights of TGF-β signaling.
format Article
id doaj-art-aecbb43694934f1ab4f7ac48b6dfb829
institution OA Journals
issn 2405-5808
language English
publishDate 2024-12-01
publisher Elsevier
record_format Article
series Biochemistry and Biophysics Reports
spelling doaj-art-aecbb43694934f1ab4f7ac48b6dfb8292025-08-20T02:19:51ZengElsevierBiochemistry and Biophysics Reports2405-58082024-12-014010186410.1016/j.bbrep.2024.101864Kinome-wide CRISPR-Cas9 screens revealed EXOSC10 as a positive regulator of TGF-β signalingDingding Wang0Xinhao Zhang1Jianxun Guo2Weijia Liu3Yanchi Zhou4Renxian Wang5JST Sarcopenia Research Centre, National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, ChinaDepartment of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing, 100005, China; Center for Bioinformatics, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, 100005, ChinaJST Sarcopenia Research Centre, National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, ChinaJST Sarcopenia Research Centre, National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, ChinaDepartment of Hepatobiliary Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, ChinaJST Sarcopenia Research Centre, National Center for Orthopaedics, Beijing Research Institute of Traumatology and Orthopaedics, Beijing Jishuitan Hospital, Capital Medical University, Beijing, 100035, ChinaThe TGF-β signaling pathway is closely associated with human health and disease, and the systematic identification of factors involved in the TGF-β signaling pathway significantly contributes to the understanding and treatment of various diseases. Through kinome-wide CRISPR screen, we identified 13 candidate regulatory targets. Notably, the well-known hallmark genes TGFBR1 and TGFBR2 emerged as the top two candidate targets. OXSR1 and EXOSC10 were ranked third and fourth as positive candidate targets, respectively, with EXOSC10 being a novel discovery. Importantly, our findings revealed the down-regulation of OXSR1 and EXOSC10 using CRISPR knockout and RNAi technology effectively suppressed the TGF-β signaling pathway in HeLa and HaCaT cells, providing new insights of TGF-β signaling.http://www.sciencedirect.com/science/article/pii/S2405580824002280TGF-β signalingEXOSC10Kinome-wide CRISPR screen
spellingShingle Dingding Wang
Xinhao Zhang
Jianxun Guo
Weijia Liu
Yanchi Zhou
Renxian Wang
Kinome-wide CRISPR-Cas9 screens revealed EXOSC10 as a positive regulator of TGF-β signaling
Biochemistry and Biophysics Reports
TGF-β signaling
EXOSC10
Kinome-wide CRISPR screen
title Kinome-wide CRISPR-Cas9 screens revealed EXOSC10 as a positive regulator of TGF-β signaling
title_full Kinome-wide CRISPR-Cas9 screens revealed EXOSC10 as a positive regulator of TGF-β signaling
title_fullStr Kinome-wide CRISPR-Cas9 screens revealed EXOSC10 as a positive regulator of TGF-β signaling
title_full_unstemmed Kinome-wide CRISPR-Cas9 screens revealed EXOSC10 as a positive regulator of TGF-β signaling
title_short Kinome-wide CRISPR-Cas9 screens revealed EXOSC10 as a positive regulator of TGF-β signaling
title_sort kinome wide crispr cas9 screens revealed exosc10 as a positive regulator of tgf β signaling
topic TGF-β signaling
EXOSC10
Kinome-wide CRISPR screen
url http://www.sciencedirect.com/science/article/pii/S2405580824002280
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AT jianxunguo kinomewidecrisprcas9screensrevealedexosc10asapositiveregulatoroftgfbsignaling
AT weijialiu kinomewidecrisprcas9screensrevealedexosc10asapositiveregulatoroftgfbsignaling
AT yanchizhou kinomewidecrisprcas9screensrevealedexosc10asapositiveregulatoroftgfbsignaling
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