Hypoxia induces hepatocellular carcinoma metastasis via the HIF-1α/METTL16/lnc-CSMD1-7/RBFOX2 axis - Details

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Abstract：

Hypoxic　microenvironment　is　clinically　associated　with　metastasis　and　poor　prognosis　of　numerous　cancers.　The　mechanisms　by　which　intratumoral　hypoxia　regulates　metastasis　are　not　fully　understood.　Our　study　identifies　a　downregulation　of　Lnc-CSMD1-7　in　hepatocellular　carcinoma　(HCC)　and　correlated　with　poor　prognosis　of　HCC　patients.　Lnc-CSMD1-7　negatively　regulated　HCC　cell　migration　and　invasion　in　vitro　and　suppressed　lung　metastasis　in　vivo.　Mechanistically,　Lnc-CSMD1-7　directly　binds　to　RBFOX2,　thereby　affecting　RBFOX2-regulated　alternative　splicing　in　epithelial　and　mesenchymal-specific　events.　More　importantly,　hypoxic　microenvironment　and　m6A　methylation　mediate　the　downregulation　of　Lnc-CSMD1-7　expression.　Specifically,　hypoxia　transcriptionally　upregulates　the　expression　of　the　m6A　methyltransferase　METTL16　via　HIF-1α,　and　METTL16　directly　binds　to　Lnc-CSMD1-7　and　downregulates　the　RNA　stability　of　Lnc-CSMD1-7　via　m6A　methylation,　ultimately　promoting　HCC　metastasis.　Our　findings　highlight　the　regulatory　function　of　the　METTL16/Lnc-CSMD1-7/RBFOX2　axis　in　modulating　hypoxia-induced　HCC　progression,　which　may　provide　potential　prognostic　and　therapeutic　targets　for　HCC　treatment.　©　2023　The　Author(s)

Keyword：

Cancer Epigenetics Molecular biology

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[ 1 ] [Wang Y.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 2 ] [Wang Y.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 3 ] [Yang Y.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 4 ] [Yang Y.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 5 ] [Yang Y.]Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
[ 6 ] [Yang Y.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 7 ] [Yang Y.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 8 ] [Dang Y.]Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, China
[ 9 ] [Guo Z.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 10 ] [Guo Z.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 11 ] [Zhuang Q.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 12 ] [Zhuang Q.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 13 ] [Zheng X.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 14 ] [Wang F.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 15 ] [Cheng N.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 16 ] [Liu X.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 17 ] [Liu X.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 18 ] [Guo W.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China
[ 19 ] [Guo W.]Department of Interventional Radiology, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fujian, Fuzhou, China
[ 20 ] [Zhao B.]The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, 350025, China
[ 21 ] [Zhao B.]Mengchao Med-X Center, Fuzhou University, Fuzhou, 350116, China

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Source ：

iScience

ISSN： 2589-0042

Year： 2023

Issue： 12

Volume： 26

4 . 6

JCR@2023

4 . 6 0 0

JCR@2023

JCR Journal Grade：1

CAS Journal Grade：2

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WoS CC Cited Count： 0

SCOPUS Cited Count： 3

ESI Highly Cited Papers on the List： 0 Unfold All

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30 Days PV： 2

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