title: Essential metabolic, anti-inflammatory, and anti-tumorigenic functions of miR-122 in liver.
abstract: miR-122, an abundant liver-specific microRNA (miRNA), regulates cholesterol metabolism and promotes hepatitis C virus (HCV) replication. Reduced miR-122 expression in hepatocellular carcinoma (HCC) correlates with metastasis and poor prognosis. Nevertheless, the consequences of sustained loss of function of miR-122 in vivo have not been determined. Here, we demonstrate that deletion of mouse Mir122 resulted in hepatosteatosis, hepatitis, and the development of tumors resembling HCC. These pathologic manifestations were associated with hyperactivity of oncogenic pathways and hepatic infiltration of inflammatory cells that produce pro-tumorigenic cytokines, including IL-6 and TNF. Moreover, delivery of miR-122 to a MYC-driven mouse model of HCC strongly inhibited tumorigenesis, further supporting the tumor suppressor activity of this miRNA. These findings reveal critical functions for miR-122 in the maintenance of liver homeostasis and have important therapeutic implications, including the potential utility of miR-122 delivery for selected patients with HCC and the need for careful monitoring of patients receiving miR-122 inhibition therapy for HCV.
authors: Molecular, Cellular, and Developmental Biology Program, The Ohio State University, Columbus, OH, USA.
authors: Shu-Hao
authors: SH
authors: Hsu
authors: Bo
authors: B
authors: Wang
authors: Janaiah
authors: J
authors: Kota
authors: Jianhua
authors: J
authors: Yu
authors: Stefan
authors: S
authors: Costinean
authors: Huban
authors: H
authors: Kutay
authors: Lianbo
authors: L
authors: Yu
authors: Shoumei
authors: S
authors: Bai
authors: Krista
authors: K
authors: La Perle
authors: Raghu R
authors: RR
authors: Chivukula
authors: Hsiaoyin
authors: H
authors: Mao
authors: Min
authors: M
authors: Wei
authors: K Reed
authors: KR
authors: Clark
authors: Jerry R
authors: JR
authors: Mendell
authors: Michael A
authors: MA
authors: Caligiuri
authors: Samson T
authors: ST
authors: Jacob
authors: Joshua T
authors: JT
authors: Mendell
authors: Kalpana
authors: K
authors: Ghoshal
mesh_terms: D020413:3' Untranslated Regions; D000818:Animals; D001483:Base Sequence; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D016207:Cytokines / Q000096:biosynthesis; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D016147:Genes, Tumor Suppressor; D016259:Genes, myc; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000097:blood; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism / Q000628:therapy; D008114:Liver Neoplasms, Experimental / Q000209:etiology / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D057507:Mice, 129 Strain; D018345:Mice, Knockout; D035683:MicroRNAs / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism* / Q000627:therapeutic use; D009000:Monocytes / Q000276:immunology / Q000473:pathology; D009504:Neutrophils / Q000276:immunology / Q000473:pathology; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; D016207:Cytokines; D008055:Lipids; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; C544354:Mirn122 microRNA, mouse; D012334:RNA, Neoplasm