MiR-30 Functions As A Tumor Suppressor By Modulating CD90 In Hepatocellular Carcinoma

ObjectiveLiver cancer is the fifth most common malignancy and is the third most causes of cancer death in the worldwide.Hepatocellular carcinoma(HCC)is the major histological subtypes of primary liver cancers,accounting for 70%to 85%of the liver cancer.Recently,several studies have been reported that miRNAs may play an important role in tumorigenesis and may act as oncogenes or tumor suppressor genes.MiR-30 family have been shown to be low expression in multiple neoplasms,may act as oncogenes or tumor suppressor genes in tumorigenesis.In present study we found that miR-30c,miR-30b,and miR-30e could regulate numerous gene transcription.Emerging evidence demonstrated that miR-30 family may play an important role in human cancers and could regulate epithelial-mesenchymal transition(EMT).EMT is a crucial process in tumorigenesis and is also important in cancer stem cells maintain "stemness" in hepatic cancer stem cells.CD90 is one of the hepatic stem cell marker and involved in numerous biological processes.However,the role of miR-30 in HCC is not clear and the mechanism of interaction with CD90 has not been reported.Our study using qRT-PCR,tissue micrroarry array,and immunohistochemistry,analysed the expression profile of miR-30 in tumor tissues and adjacent tissues.In addition,we explored the relationship between miR-30 family and CD90 protein expression was analyzed.MethodsIn our molecular epidemiological study,93 and 121 hepatocellular carcinoma patients with both tumor tissues and adjacent tissues samples were first investigated by the epidemiological survey.we measured the expression of miR-30c,miR-30b,and miR-30e in 93 tumor tissues and adjacent tissues by real-time RT-PCR.And 121 tumor tissues from an independent cohort were selected to measure the expression level of miR-30 family and CD90 by immunohistochemistry(IHC).Expolre the role of CD90 protein in hepatocellular carcinoma and the association between miR-30 family and CD90 in hepatocellular carcinoma.Disscussing the molecular mechanisms of miR-30 in hepatocellular carcinoma.Results1.Significant decrease in the expression levels of miR-30c,miR-30b,and miR-30e were noted in the tumor tissues compared to the paired tumor-adjacent tissues.2.The expression of CD90 protein was significantly different between tumor tissues and paired tumor-adjacent tissues.3.Significantly differential expression of miR-30c and miR-30e was observed between negative and positive staining of CD90 protein.4.For miR-30c,significantly lower expression was noted in smoker and drinker when compared to non-smoker and non-drinker in 214 HCC patients.For miR-30b,we found that the expression level was significantly lower in ever smoke than non-smoke patients and in serum a-fetoprotein positive than negative patients in 214 HCC patients.For miR-30e,the expression levels were significantly lower in smoke than non-smoke patients,in a-fetoprotein positive than negative patients,and in HBV positive than negative patients in 214 HCC patients.5.The expression of miR-30 was significantly different between serum a-fetoprotein positive and negative in smoker,drinker and female.Conclusion1.MiR-30 family may be act as a tumor suppressor in HCC and the expression levels effected by smoking and drinking behavivor factors.MiR-30 family were associated with the expression of serum AFP,especially in smoker,drinker and female HCC patients.In addition,miR-30 family were associated with the HBV virus transcription.There was no evidence of miR-30 on hepatocellular carcinoma prognosis.2.The expression of CD90 protein was significantly different between tumor tissues and paired tumor-adjacent tissues.CD90 protein may be a tumor suppressor in HCC development3.miR-30 family may modulate CD90 expression by direct targeting snail1 through TGF-p signal pathway and may be play an important role in tumorigenesis in HCC,Further studies are warranted to validate these findings.