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MicroRNA-483-5p Inhibits Hepatocellular Carcinoma Cell Proliferation, Cell Steatosis, and Fibrosis by Targeting PPARα and TIMP2
by
Qi, Qi
, Ressom, Habtom W.
, Gadi, Sashi
, Gyamfi, Maxwell Afari
, Chimeh, Uchechukwu
, Vandana
, Rios-Colon, Leslimar
, Kumar, Deepak
, Varghese, Rency S.
, Niture, Suryakant
in
3' Untranslated regions
/ Apoptosis
/ Biomarkers
/ Cell migration
/ Cell proliferation
/ Cirrhosis
/ Fatty liver
/ Fibrosis
/ Gene expression
/ Health aspects
/ Hepatitis
/ Hepatocellular carcinoma
/ Hepatocytes
/ Hepatoma
/ High fat diet
/ Kinases
/ Liver cancer
/ Liver diseases
/ MicroRNA
/ MicroRNAs
/ miRNA
/ Prevention
/ Steatosis
/ Therapeutic targets
/ Tissue inhibitor of metalloproteinase 2
/ Tumor suppressor genes
/ Tumors
2023
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MicroRNA-483-5p Inhibits Hepatocellular Carcinoma Cell Proliferation, Cell Steatosis, and Fibrosis by Targeting PPARα and TIMP2
by
Qi, Qi
, Ressom, Habtom W.
, Gadi, Sashi
, Gyamfi, Maxwell Afari
, Chimeh, Uchechukwu
, Vandana
, Rios-Colon, Leslimar
, Kumar, Deepak
, Varghese, Rency S.
, Niture, Suryakant
in
3' Untranslated regions
/ Apoptosis
/ Biomarkers
/ Cell migration
/ Cell proliferation
/ Cirrhosis
/ Fatty liver
/ Fibrosis
/ Gene expression
/ Health aspects
/ Hepatitis
/ Hepatocellular carcinoma
/ Hepatocytes
/ Hepatoma
/ High fat diet
/ Kinases
/ Liver cancer
/ Liver diseases
/ MicroRNA
/ MicroRNAs
/ miRNA
/ Prevention
/ Steatosis
/ Therapeutic targets
/ Tissue inhibitor of metalloproteinase 2
/ Tumor suppressor genes
/ Tumors
2023
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MicroRNA-483-5p Inhibits Hepatocellular Carcinoma Cell Proliferation, Cell Steatosis, and Fibrosis by Targeting PPARα and TIMP2
by
Qi, Qi
, Ressom, Habtom W.
, Gadi, Sashi
, Gyamfi, Maxwell Afari
, Chimeh, Uchechukwu
, Vandana
, Rios-Colon, Leslimar
, Kumar, Deepak
, Varghese, Rency S.
, Niture, Suryakant
in
3' Untranslated regions
/ Apoptosis
/ Biomarkers
/ Cell migration
/ Cell proliferation
/ Cirrhosis
/ Fatty liver
/ Fibrosis
/ Gene expression
/ Health aspects
/ Hepatitis
/ Hepatocellular carcinoma
/ Hepatocytes
/ Hepatoma
/ High fat diet
/ Kinases
/ Liver cancer
/ Liver diseases
/ MicroRNA
/ MicroRNAs
/ miRNA
/ Prevention
/ Steatosis
/ Therapeutic targets
/ Tissue inhibitor of metalloproteinase 2
/ Tumor suppressor genes
/ Tumors
2023
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MicroRNA-483-5p Inhibits Hepatocellular Carcinoma Cell Proliferation, Cell Steatosis, and Fibrosis by Targeting PPARα and TIMP2
Journal Article
MicroRNA-483-5p Inhibits Hepatocellular Carcinoma Cell Proliferation, Cell Steatosis, and Fibrosis by Targeting PPARα and TIMP2
2023
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Overview
MicroRNAs (miRNAs) are small non-coding RNA molecules that bind with the 3′ untranslated regions (UTRs) of genes to regulate expression. Downregulation of miR-483-5p (miR-483) is associated with the progression of hepatocellular carcinoma (HCC). However, the significant roles of miR-483 in nonalcoholic fatty liver disease (NAFLD), alcoholic fatty liver diseases (AFLD), and HCC remain elusive. In the current study, we investigated the biological significance of miR-483 in NAFLD, AFLD, and HCC in vitro and in vivo. The downregulation of miR-483 expression in HCC patients’ tumor samples was associated with Notch 3 upregulation. Overexpression of miR-483 in a human bipotent progenitor liver cell line HepaRG and HCC cells dysregulated Notch signaling, inhibited cell proliferation/migration, induced apoptosis, and increased sensitivity towards antineoplastic agents sorafenib/regorafenib. Interestingly, the inactivation of miR-483 upregulated cell steatosis and fibrosis signaling by modulation of lipogenic and fibrosis gene expression. Mechanistically, miR-483 targets PPARα and TIMP2 gene expression, which leads to the suppression of cell steatosis and fibrosis. The downregulation of miR-483 was observed in mice liver fed with a high-fat diet (HFD) or a standard Lieber-Decarli liquid diet containing 5% alcohol, leading to increased hepatic steatosis/fibrosis. Our data suggest that miR-483 inhibits cell steatosis and fibrogenic signaling and functions as a tumor suppressor in HCC. Therefore, miR-483 may be a novel therapeutic target for NAFLD/AFLD/HCC management in patients with fatty liver diseases and HCC.
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