High Expression Of MiR-105-1 Positively Correlates With Clinical Prognosis Of Hepatocellular Carcinoma By Targeting Oncogene NCOA1

Objective Growing evidence indicates that micro RNA plays a critical role in tumorigenesis and development by regulating their targets respectively.This study screens potentially liver-relevant miR-105-1 and its target gene NCOA1,then verifies the expression levels of miR-105-1 and its target gene NCOA1 in hepatocellular carcinoma and normal hepatic tissues as well as the relationship between them,and analyses the prognosis of the patients with hepatocellular carcinoma.This study is aimed at the underlying mechanism of miR-105-1 in hepatocellular carcinoma carcinogenesis and development.Methods Potentially liver-relevant miR-105-1 was screened by using gene microarray and hierarchical cluster analysis and 34 pairs of human hepatocellular carcinoma tissues and corresponding adjacent tissues as well as additional 120 liver cancer tissues were collected,then the differential expression of miR-105-1 was detected and verified in hepatocellular carcinoma and adjacent normal tissues by real-time quantitative polymerase chain reaction(q RT-PCR),and the relation of miR-105-1 to the prognosis of patients was further analysed.The potential target gene NCOA1 of miR-105-1 was searched by the database.In addition,q RT-PCR,Western-Blot,cell proliferation assay and immunohistochemistry of hepatocellular carcinoma were used to test the targeting relationships between miR-105-1 and NCOA1,and the performance of miR-105-1 and NCOA1 in patients' prognosis were analysed jointly.Results It was suggested that miR-105-1 maybe our newly discovered differential gene by data analysis from GEO and TCGA database.The expression of miR-105-1 was detected in both hepatocellular carcinoma and adjacent normal tissues.Mi R-105-1 was downregulated by 0.59 times in the 34 pairs of HCC and adjacent normal tissues(P=0.041),and miR-105-1 was downregulated by 0.51 times in 154 HCC tissues compared with 34 adjacent normal tissues(P=0.032).The value of Log-Rank P in Kaplan-Meier survival analysis OS of miR-105-1 in 154 HCC tissues was 0.031,which demonstrated that the low expression level of miR-105-1 resulted in the short survival time of HCC patients.The value of Log-Rank P of PFS was 0.038,which confirmed that the low expression level of miR-105-1 led to the short duration of disease progression.There was a prediction that NCOA1 may be the target gene of miR-105-1 through GEO database and three target gene prediction sites,and the impact of miR-105-1 mimics(overexpression)and inhibitor(knock-down)on the content of NCOA1 m RNA was detected by Hela cell's real-time quantitative polymerase chain reaction(q RT-PCR).In the verification test,the expression level of NCOA1 was lower(P<0.001)in miR-105-1-overexpression-group and higher(P<0.001)in miR-105-1-knockout-group compared with the control group in the RT-PCR detection of Hela cell.WB detected the impact made by the overexpression and knockout of miR-105-1 on NCOA1 and well-known downstream CSF1 protein levels.Compared with the control group,the expression levels of NCOA1 and well-known downstream CSF1 protein decreased when miR-105-1 overexpressed and increased when miR-105-1 was knockout.Ectopic-expressed miR-105-1 reduced the activity of luciferase which was located within 3'untranslated region(3'UTR)of NCOA1.However,three mutant nucleosides that miR-105-1 mutant contained did not inhibit luciferase activity.In the paraffin sections' histochemistry of cancer tissues and adjacent tissues,a phenomenon was found that high levels of NCOA1 expression in normal hepatic tissues and low levels of NCOA1 expression in hepatocellular carcinoma tissues.The value of Log-Rank P in Kaplan-Meier survival analysis OS of NCOA1 in 154 HCC tissues was 0.011,which illustrated that the high expression level of NCOA1 led to the short survival time of HCC patients.The value of Log-Rank P of PFS was 0.033,which explained that the low expression level of NCOA1 resulted in the short duration of disease progression.Mi R-105-1 and NCOA1 in HCC were jointly analysed and the value of Log-Rank P was less than 0.001.This result suggested that the lower miR-105-1 level and the higher NCOA1 expression level were,the shorter HCC patients' survival time was.The value of Log-Rank P of PFS was 0.002,which proved that the lower miR-105-1 level and the higher NCOA1 expression level were,the shorter duration HCC patients' disease progression was.Conclusion 1.The expression of miR-105-1 is higher in HCC than in normal hepatic tissues.2.Mi R-105-1 may regulate the tumorigenesis and development of HCC by controlling its target gene NCOA1.3.The prognosis of HCC patients with high expression level of miR-105-1 is well.On the contrary,the prognosis of HCC patients with low expression level of miR-105-1 is not satisfactory.4.The prognosis of HCC patients with high expression level of NCOA1 is not well.On the contrary,the prognosis of HCC patients with low expression level of NCOA1 is satisfactory.5.Mi R-105-1 and NCOA1 may be the potential significant biomarkers in prognosis prediction of HCC.