title: miRNA-548p suppresses hepatitis B virus X protein associated hepatocellular carcinoma by downregulating oncoprotein hepatitis B x-interacting protein.
abstract: OBJECTIVE
  miR-548p is a recently identified and poorly characterized miRNA. However, its role of miR-548p in tumorigenesis and progression remains poorly understood. Here, we aimed to investigate the biofunction of miR-548p in hepatocellular carcinogenesis.
  
  
  METHODS
  The expression levels of miR-548p were detected by quantitative reverse transcription polymerase chain reaction (qRT-PCR). The role of miR-548p in hepatocellular carcinoma (HCC) was determined by colony formation, flow cytometry assay and nude mice xenograft experiments. miR-548p target genes were analyzed by miRNA target predication programs and verified by qRT-PCR, western blotting assay and dual-luciferase reporter assay.
  
  
  RESULTS
  miR-548p is repressed by hepatitis B virus X protein (HBx) in HCC tumor tissues and hepatoma cells, and inhibited cell growth by inhibiting cell proliferation and promoting cell apoptosis. miR-548p directly downregulated the expression of hepatitis B x-interacting protein (HBXIP) by binding to the 3'-untranslated region of HBXIP mRNA. Further study showed that hepatocyte nuclear factor-4a (HNF4A) promoted the expression of miR-548p and inhibited the transcription of HBXIP. HNF4A is a dominant transcriptional regulator of hepatocyte differentiation and hepatocellular carcinogenesis, and is shown to be repressed by HBx.
  
  
  CONCLUSIONS
  We proposed the model for HBx/HNF4A/miR-548p/HBXIP pathway that controls hepatoma cell growth and tumorigenesis of HCC. miR-548p was identified as a tumor-suppressor in HBx-associated hepatocellular carcinogenesis.
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Xiu-Mei
authors.initials: XM
authors.lastname: Hu
authors.affiliation: Research Center of Clinical Medicine, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Yan
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yan-Wei
authors.initials: YW
authors.lastname: Hu
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Jin-Lan
authors.initials: JL
authors.lastname: Huang
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Shun-Wang
authors.initials: SW
authors.lastname: Cao
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Ting-Yu
authors.initials: TY
authors.lastname: Ren
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Yue-Ting
authors.initials: YT
authors.lastname: Tang
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Li
authors.initials: L
authors.lastname: Lin
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Laboratory Medicine Center, Nanfang Hospital, Southern Medical University, Guangzhou, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
keywords: hepatitis B virus X protein; hepatitis B x-interacting protein; hepatocellular carcinoma; hepatocyte nuclear factor-4a; miR-548p