Research Of Expression And Molecular Mechanism Of NKILA In Hepatocellular Carcinoma

BackgroundHepatocellular Carcinoma(HCC)is one of the most prevalent cancers in China.HCC progress rapidly without typical symptoms.Due to its high recurrence and metastasis rate,the prognosis of HCC is very dismal.Although the prognosis in recent years has increased due to comprehensive treatment based on surgery,the five-year overall survival rate is still less than 30%.It has become an urgent to investigate new molecular target and biomarkers for HCC.Long non-coding RNA(LncRNA)is a class of non-coding RNA,which length is more than 200 nucleotides.LncRNA was previously recognized as a "noise" of gene transcription.However,recent researches has found LncRNA can be critical in the regulation of cell biological functions,and LncRNA is involved in cell proliferation,differentiation,Epithelial-Mesenchymal Transition(EMT).NKILA(NF-kappaB interacting LncRNA)is a LncRNA fisrt reported by Chinese researchers.It influence NF-KappaB(Nuclear factor Kappa-B)pathway actiavation by blocking the Phosphorylation of IKB(NF-KappaB inhibitor).Although many studies proved NKILA can be critical in the regulation of metastasis,such as breast cancer non-small cell lung cancer etc,the mechanism of NKILA in HCC remains unknown.MethodsThe samples of 146 cases of HCC tissues and matched peritumoral tissues,HCC cell lines and normal hepatocyte cell lins were collected and RNA extracted,and NKILA expression was detected by qRT-PCR.Then NKILA overexpressed HCC cell lines were established by lentivirus,and transwell assay were performed to investigate the role of NKILA in cell migration and invasion.Western blot were used to evaluate the molecular changes in NK-kappaB pathway and EMT.At last pulmonary metastasis model was established to investigate the role of NKILA in vivo.Results:1.Compared to the peritumoral tissues and normal hepatocyte cell lines,NKILA was down regulated in HCC tissues and HCC cell lines.2.In the in vitro experiment based on SMMC-7721 cell lines,the migration and invasion decreased in NKILA overexpressed groups.And compare to the control groups,the IKB phosphorylation(representing the NF-kappaB activation)and EMT related protein(MMP family,SLUG,Vimentin)expression level was decreased in NKILA overexpression groups.3.In the in vitvo experiment based on SMMC-7721 cell lines,the pulmonary metastasis decreased in NKILA overexpression group.Conclusion:NKILA is down regulated in HCC tissues and HCC cell lines.NKILA regulates cell migration and invasion by interrupting NK-kappaB activation and EMT.Overexpression of NKILA leads to decrease in migration and invasion NKILA could be a novel biomarker as a promising diagnostic molecule and therapeutic target.