WTAP-mediated m6A modification on circCMTM3 inhibits hepatocellular carcinoma ferroptosis by recruiting IGF2BP1 to increase PARK7 stability

Chen, Shuwei; Xia, Hongxiang; Sheng, Langqing

doi:10.1016/j.dld.2022.12.005

Cited by 19 publications

(10 citation statements)

References 35 publications

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“…Additionally, through RIP and MERIP experiments, we established a direct interaction between WTAP and ULK1, clarifying WTAP’s role in modulating the m6A modification level of ULK1 mRNA. Prior studies have indicated that WTAP can regulate the mRNA stability of its target genes [ 37 – 41 ]. In line with these findings, our study also showed that WTAP affects the stability of ULK1 mRNA.…”

Section: Discussionmentioning

confidence: 99%

Regulation of ULK1 by WTAP/IGF2BP3 axis enhances mitophagy and progression in epithelial ovarian cancer

Wang,

Zheng,

Wang

et al. 2024

Cell Death Dis

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There is a pressing need for innovative therapeutic strategies for patients with epithelial ovarian cancer (EOC). Previous studies have shown that UNC-51-like kinase 1 (ULK1), a serine/threonine kinase, is crucial in regulating cellular autophagy and mitophagy across various tumor types. However, the clinical implications, biological functions, and potential mechanisms of ULK1 in EOC remain poorly understood. This study demonstrates that ULK1 expression is upregulated in EOC tissue samples and EOC cell lines, with increased ULK1 expression correlating with poor prognosis. Functionally, overexpressed ULK1 enhances the proliferation and migration abilities of EOC cells both in vitro and in vivo. Mechanistically, ULK1 was identified as an m6A target of WTAP. WTAP-mediated m6A modification of ULK1 enhanced its mRNA stability in an IGF2BP3-dependent manner, leading to elevated ULK1 expression and enhanced mitophagy in EOC. In summary, our research reveals that the WTAP/IGF2BP3-ULK1 axis significantly influences protective mitophagy in EOC, contributing to its progression. Therefore, the regulatory mechanisms and biological function of ULK1 identify it as a potential molecular target for therapeutic intervention in EOC.

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Section: Discussionmentioning

confidence: 99%

Regulation of ULK1 by WTAP/IGF2BP3 axis enhances mitophagy and progression in epithelial ovarian cancer

Wang,

Zheng,

Wang

et al. 2024

Cell Death Dis

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show abstract

“…WTAP-mediated m 6 A modification on circCMTM3 inhibits ferroptosis in hepatocellular carcinoma by recruiting IGF2BP1 to increase PARK7 stability ( Chen et al, 2023 ). WTAP also can regulate NUPR1 m 6 A modification to upregulate LCN2, thereby promoting the proliferation, migration and invasion of breast cancer ( Tan et al, 2023 ).…”

Section: A Modification Regulates the Occurrence Of Ferroptosismentioning

confidence: 99%

Correlation between RNA N6-methyladenosine and ferroptosis in cancer: current status and prospects

Liu,

Lv,

Cai

et al. 2024

Front. Cell Dev. Biol.

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N6-methyladenosine (m6A) is the most abundant chemical modification in eukaryotic cells. It is a post-transcriptional modification of mRNA, a dynamic reversible process catalyzed by methyltransferase, demethylase, and binding proteins. Ferroptosis, a unique iron-dependent cell death, is regulated by various cell metabolic events, including many disease-related signaling pathways. And different ferroptosis inducers or inhibitors have been identified that can induce or inhibit the onset of ferroptosis through various targets and mechanisms. They have potential clinical value in the treatment of diverse diseases. Until now, it has been shown that in several cancer diseases m6A can be involved in the regulation of ferroptosis, which can impact subsequent treatment. This paper focuses on the concept, function, and biological role of m6A methylation modification and the interaction between m6A and ferroptosis, to provide new therapeutic strategies for treating malignant diseases and protecting the organism by targeting m6A to regulate ferroptosis.

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“…Mechanistically, deletion of WTAP can result in G2/M arrest in HCC in a p21/p27-dependent fashion with the involvement of ETS proto-oncogene 1 (ETS1) ( Chen et al, 2019 ). Second, Chen et al reported WTAP promotes HCC carcinogenesis by altering the m 6 A methylation of CircCMTM3, thus suppressing HCC ferroptosis ( Chen S. et al, 2022 ). KIAA1429 is also highly expressed in HCC tissues, and high expression of KIAA1429 indicates the poor outcome of HCC patients.…”

Section: The Implications Of M 6 a Regulators In H...mentioning

confidence: 99%

Landscape of m6A RNA methylation regulators in liver cancer and its therapeutic implications

Zhao,

Li,

et al. 2024

Front. Pharmacol.

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Liver cancer remains as the third leading cause of cancer-related death globally as of 2020. Despite the significant progress made in the field of liver cancer treatment, there is still a lack of effective therapies in patients with advanced cancer and the molecular mechanisms underlying liver cancer progression remain largely elusive. N6-methyladenosine (m6A) modification, as the most prevalent and abundant internal RNA modification in eukaryotic RNAs, plays an essential role in regulating RNA metabolism including RNA splicing, stability, translation, degradation. To date, there is mounting evidence showing that m6A dysregulation is closely associated with the onset and development of many tumors including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC) and hepatoblastoma (HB). In this review, we summarize the last research progress regarding the functions of m6A-related regulators in liver cancer and its underlying mechanisms. Additionally, we also discuss the therapeutic applications of m6A-based inhibitors in liver cancer treatment.

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WTAP-mediated m6A modification on circCMTM3 inhibits hepatocellular carcinoma ferroptosis by recruiting IGF2BP1 to increase PARK7 stability

Cited by 19 publications

References 35 publications

Regulation of ULK1 by WTAP/IGF2BP3 axis enhances mitophagy and progression in epithelial ovarian cancer

Regulation of ULK1 by WTAP/IGF2BP3 axis enhances mitophagy and progression in epithelial ovarian cancer

Correlation between RNA N6-methyladenosine and ferroptosis in cancer: current status and prospects

Landscape of m6A RNA methylation regulators in liver cancer and its therapeutic implications

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