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MiR-186-5p prevents hepatocellular carcinoma progression by targeting methyltransferase-like 3 that regulates m6A-mediated stabilization of follistatin-like 5

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机构: [1]Department of General Surgery, The First Affiliated Hospital of BengBu Medical College, BengBu, 233000, China [2]Liver Transplantation Center and Hepatobiliary and Pancreatic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China [3]The University of Texas MD Anderson Cancer Center, Department of Translational Molecular Pathology, Houston, USA
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关键词: microRNA Hepatocellular carcinoma METTL3 FSTL5 mRNA stability

摘要:
Hepatocellular carcinoma (HCC) is a multistep process involving sophisticated genetic, epigenetic, and transcriptional changes. However, studies on microRNA (miRNA)'s regulatory effects of N6-methyladenosine (m6A) modifications on HCC progression are limited.Cell Counting Kit-8 (CCK-8), clone formation, and Transwell assays were used to investigate changes in cancer cell proliferation, invasion, and migration. RNA m6A levels were verified using methylated RNA immunoprecipitation. Luciferase reporter assay was used to study the potential binding between miRNAs and mRNA. A mouse tumor transplant model was established to study the changes in tumor progression.Follistatin-like 5 (FSTL5) was significantly downregulated in HCC and inhibited its further progression. Additionally, methyltransferase-like 3 (METTL3) reduced FSTL5 mRNA stability in an m6A-YTH domain family 2(YTHDF2)-dependent manner. Functional experiments revealed that METTL3 downregulation inhibited HCC progression by upregulating FSTL5 in vitro and in vivo. Luciferase reporter assay verified that miR-186-5p directly targets METTL3. Additionally, miR-186-5p inhibits the proliferation, migration, and invasion of HCC cells by downregulating METTL3 expression.The miR-186-5p/METTL3/YTHDF2/FSTL5 axis may offer new directions for targeted HCC therapy.© 2024 The Authors. Published by Elsevier Ltd.

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大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
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大类 | 3 区 综合性期刊
小类 | 3 区 综合性期刊
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Q1 MULTIDISCIPLINARY SCIENCES
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Q1 MULTIDISCIPLINARY SCIENCES

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第一作者机构: [1]Department of General Surgery, The First Affiliated Hospital of BengBu Medical College, BengBu, 233000, China [2]Liver Transplantation Center and Hepatobiliary and Pancreatic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China
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通讯机构: [1]Department of General Surgery, The First Affiliated Hospital of BengBu Medical College, BengBu, 233000, China [3]The University of Texas MD Anderson Cancer Center, Department of Translational Molecular Pathology, Houston, USA [*1]Department of General Surgery, The First Affiliated Hospital of Bengbu Medical College, NO. 287, Changhuai Road, Longzihu district, Bengbu, 233000, Anhui, China [*2]Department of General Surgery, The First Affiliated Hospital of Bengbu Medical College, NO. 287, Changhuai Road, Longzihu district, Bengbu, 233000, Anhui, China
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