title: MicroRNA-363-mediated downregulation of S1PR1 suppresses the proliferation of hepatocellular carcinoma cells.
abstract: S1PR1 plays a crucial role in promoting proliferation of hepatocellular carcinoma (HCC). Over expression of S1PR1 is observed in HCC cell lines. The mechanisms underlying the aberrant expression of S1PR1 are not known well. MircroRNAs are important regulators of gene expression and disproportionate microRNAs can result in dysregulation of oncogenes in cancer cells. In this study, we found that miR-363, a potential tumor suppressor microRNA, downregulated the expression of S1PR1 and inhibited the proliferation of HCC cells. Bioinformatic analysis predicted a putative binding site of miR-363 within the 3'-UTR of S1PR1 mRNA. Luciferase reporter assay showed that miR-363 directly targeted the 3'-UTR of S1PR1 mRNA. Transfection of miR-363 mimics suppressed S1PR1 expression in HCC cells, followed by the repression of the activation of ERK and STAT3. Moreover, we found that the expression of downstream genes of ERK and STAT3, including PDGF-A, PDGF-B, MCL-1 and Bcl-xL, was suppressed after miR-363 transfection. Taken together, the present study demonstrated that miR-363 was a negative regulator of S1PR1 expression in HCC cells and inhibited cell proliferation, suggesting that the miR-363/S1PR1 pathway might be a novel target for the treatment of HCC.
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Zhou
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Huang
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yuanyin
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhong
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Zeng
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Center for Pharmacogenetics, Department of Pharmaceutical Sciences, School of Pharmacy, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Song
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Biochemistry and Molecular Biology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China. Electronic address: hefengtian06@aliyun.com.
authors.forename: Fengtian
authors.initials: F
authors.lastname: He
mesh_terms: D020413:3' Untranslated Regions; D001483:Base Sequence; D001665:Binding Sites; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism; D049109:Cell Proliferation; D015536:Down-Regulation; D048049:Extracellular Signal-Regulated MAP Kinases; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism; D035683:MicroRNAs / Q000502:physiology*; D034622:RNA Interference; D049349:Receptors, Lysosphingolipid / Q000235:genetics* / Q000378:metabolism; D050796:STAT3 Transcription Factor / Q000378:metabolism; D000081025:Sphingosine-1-Phosphate Receptors
chemical_list: D020413:3' Untranslated Regions; C574861:MIRN363 microRNA, human; D035683:MicroRNAs; D049349:Receptors, Lysosphingolipid; C477362:S1PR1 protein, human; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D000081025:Sphingosine-1-Phosphate Receptors; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Hepatocellular carcinoma; MicroRNA-363; Proliferation; Sphingosine-1-phosphate receptor-1