HIF-1α-induced expression of m6A reader YTHDF1 drives hypoxia-induced autophagy and malignancy of hepatocellular carcinoma by promoting ATG2A and ATG14 translation
作者机构：Hepatobiliary CenterThe First Affiliated Hospital of Nanjing Medical UniversityKey Laboratory of Liver TransplantationChinese Academy of Medical SciencesNHC Key Laboratory of Living Donor Liver Transplantation(Nanjing Medical University)NanjingJiangsu ProvinceChina School of MedicineSoutheast UniversityNanjingChina department of Hepatopancreatobiliary SurgeryShenzhen Second People's HospitalThe First Affiliated Hospital of Shenzhen UniversityShenzhenGuangdongChina Department of Hepatobiliary SurgeryThe Affiliated Drum Tower Hospital of Nanjing University Medical SchoolNanjingJiangsu ProvincePeople's Republic of China Medical School of Nanjing UniversityNanjingJiangsuChina Department of OncologyThe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina Department of ImmunologyKey Laboratory of Immune Microenvironment and DiseaseNanjing Medical UniversityNanjingJiangsu ProvinceChina Department of General SurgeryThe First Affiliated Hospital of Nanjing Medical UniversityNanjingJiangsu ProvinceChina
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2021年第6卷第3期
页 面：988-1000页
核心收录：
学科分类：0710[理学-生物学] 1002[医学-临床医学] 1001[医学-基础医学(可授医学、理学学位)] 100214[医学-肿瘤学] 10[医学]
基 金：supported by the Major Program of the National Natural Science Foundation of China(Grant No.81530048,31930020) Key Laboratory of Liver Transplantation,Chinese Academy of Medical Sciences(Grant No.2017PT32008,2018PT31043,2019PT320015) the National Natural Science Foundation of China(Grant No.81870488,81872365,81972266,81772569) the Shenzhen Foundation of Science and Technology(Grant No.JCYJ20170817172116272) the Sanm ing Project of Medicine in Shenzhen(Grant No.SZSM201812079)
主 题：malignancy hepatocellular inhibited
摘 要：N6-methyladenosine(m6A),and its reader protein YTHDF1,play a pivotal role in human tumorigenesis by affecting nearly everystage of RNA *** activation is one of the ways by which cancer cells survive ***,the possibleinvolvement of m6A modification of mRNA in hypoxia-induced autophagy was unexplored in human hepatocellular carcinoma(HCO).In this study,specific variations in YTHDF1 expression were detected in YTHDF1-overexpressing,knockout,and-knockdownHCC cells,HCC organoids,and HCC patient-derived xenograft(PDX)murine ***1 expression and hypoxia inducedautophagy were significantly correlated in vitro;signifhcant overexpression of YTHDF1 in HCC tissues was associated with poorprognosis,Multivariate cox regression analysis identihed YTHDF1 expression as an independent prognostic factor in patients *** HC models conhrmed that YTHDF1 deficiency inhibited HCC autophagy,growth,and *** reporterassays and chromatin immunoprecipitation demonstrated that HlIF-1a regulated YTHDF1 transcription by directly binding to itspromoter region under *** results of methylated RNA immunoprecipitation sequencing,proteomics,and polysomeprofling indicated that YTHDF1 contibuted to the translation of autophagy-related genes ATG2A and ATG14 by binding to m6A-modifhed ATG2A and ATG14 mRNA,thus facilitating autophagy and autophagy-related malignancy of *** together,HlE-1d-induced YTHDF1 expression was associated with hypoxia-induced autophagy and autophagy-related HCC progression via promoting translation of autophagy-related genes ATG2A and ATG14 in a m6A-dependent *** fndings suggest thatYTHDF1 is a potential prognostic biomarker and therapeutic target for patients with HCC.
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