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• W4386021738 abstract "ABSTRACTFerroptosis is an important mode of regulated cell death (RCD). Its inhibition is closely related to therapeutic resistance and poor prognosis in hepatocellular carcinoma (HCC). Previous reports have demonstrated ferroptosis as a biological process highly dependent on selective autophagy, such as ferritinophagy, lipophagy, and clockophagy. Our study also revealed a role for ER-phagy-mediated ferroptosis in HCC cells treated with multi-targeted tyrosine kinase inhibitors (TKIs). In the current study, we found that the homologous circular RNA (circRNA) of the family with sequence similarity 134, member B (FAM134B), hsa_circ_0128505 (was abbreviated as circFAM134B in the present study), was identified to specifically target ER-phagy to promote lenvatinib (LV)-induced ferroptosis using reactive oxygen species (ROS), Fe2+, malondialdehyde (MDA), and western blot (WB) assays in HCC cells. RNA pull-down and mass spectrometry analyses suggested that circFAM134B and FAM134B mRNA were enriched with several common interacting proteins. Among them, poly (A) binding protein cytoplasmic 4 (PABPC4) was identified as the most enriched binding partner. It was proven to be a novel antagonist against the nonsense-mediated mRNA decay (NMD) mechanism. We then applied RNA immunoprecipitation (RIP), RNA pull-down, luciferase reporter, and NMD reporter gene assays to further explore the exact role and underlying mechanism of circFAM134B-PABPC4-FAM134B axis in HCC cells. circFAM134B was confirmed as a sponge that competitively interacted with PABPC4, thereby influencing FAM134B mRNA nonsense decay. Our results provide novel evidences and strategies for the comprehensive treatment of HCC.KEYWORDS: Hepatocellular carcinomaferroptosislenvatinibcircFAM134BPABPC4nonsense-mediated mRNA decay Disclosure statementNo potential conflict of interest was reported by the authors.Authors’ contributionsJie Li, Zhiqian Liu, Tao Bi designed this study and wrote the manuscript. Tao Bi performed the experimental work. Qianqian Lu, Xiaohong Pan provided the majority of statistical analysis as well as provided the figures and tables for the manuscript. Fenglin Dong, Yejia Hu, Zongzhen Xu, and Peng Xiu collected a large amount of data for the dataset. All authors have read and approved the final manuscript.Author consent for publicationConsent for publication was obtained from each author.Availability of data and materialsThe datasets used during the present study are available from the corresponding authors on reasonable request.Ethics approval and consent to participateThis study was approved by the Animal Care and Use Committee of the Shandong Provincial Qianfoshan Hospital.Supplementary materialSupplemental data for this article can be accessed online at https://doi.org/10.1080/15384101.2023.2249302Additional informationFundingThis work was financed by grants from the National Natural Science Foundation of China (No. 82172830 and No. 81802414), and Shandong First Medical University (Shandong Academy of Medical Sciences) Youth Science Foundation Cultivation Program (No. 202201-097)." @default.
• W4386021738 created "2023-08-22" @default.
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• W4386021738 date "2023-08-21" @default.
• W4386021738 modified "2023-10-09" @default.
• W4386021738 title "<i>circFAM134B</i> is a key factor regulating reticulophagy-mediated ferroptosis in hepatocellular carcinoma" @default.
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