Hepatocellular Carcinoma

HBV[Viral RNA]

miR-15a[miRNA]

SMAD7[mRNA]

Liver Tissues

Hepatitis B virus (HBV)

J Virol 2015 Mar 89, 2739-49 doi:10.1128/jvi.02784-14 PMID:25540364

HBV regulates apoptosis and tumorigenesis through miR15a-Smad7-TGF-B pathway

Western blot;qRT-PCR;luciferase reporter assays

We examined the protein level of Smad7 in miR-15a transfected cells. The immunoblotting data showed that the protein level of Smad7 was significantly reduced in miR-15a transfected cells data showed that miR-15a can reduce the relative luciferase activity of pGLO-Smad7 3’UTR but not pGLO-Smad7 3’UTR-mut we examined the amount of Smad7 mRNA in HBV-transgenic BALB/c mice by real-time PCR. The data showed that the relative amount of Smad7 mRNA in liver tissue of HBV-transgenic BALB/c mice was 2-fold higher than that in control mice (p<0.01). We next examined the correlation between miR-15a and Smad7 mRNA in liver tissue from HCC patients which were all chronic HBV carriers. There was negative correlation between miR-15a and Smad7 mRNA levels. We then analyzed the levels of Smad7 mRNA and HBV transcripts in liver tissue from the HCC patients by real-time PCR. miR-15a mimic enhances the activation of TGF-B luciferase reporter while miR-15a inhibitor inhibits the activation of TGF-B signaling. In conclusion, we demonstrate that HBV mRNAs act as ceRNAs of miR-15a and regulate TGF-B signaling in the development of HBV-related HCC.