The Role And Clinical Significance Of Long Non-coding RNA In Hepatocellular Carcinoma

Long non-coding RNAs(lnc RNAs)are a class of RNAs that are more than 200 nt long with low or no protein coding potential.Lnc RNAs play important roles in various physiological and pathological processes due to their ability to regulate gene expression through epigenetic,transcriptional and post-transcriptional modulation.For cancers,lnc RNA may be involved in the carcinogenesis and development of disease by promoting or suppressing cancer,and the aberrant expression of lnc RNA is also an important molecular marker for predicting susceptibility,prognosis and outcome of cancers.In this study,the role and potential molecular mechanism of lnc RNA uc002 yug 2 on hepatocellular carcinoma(HCC)were investigated.First,the expression of uc002 yug 2 in HCC tissue and adjacent normal tissues was detected by q RT-PCR,and the level of uc002 yug.2 in HCC tissues was significantly higher than that in adjacent normal tissues,which indicated the correlation between uc002 yug.2 and HCC.Furthermore,we have successfully constructed HCC cell lines with stable overexpression and stable knockdown of uc002 yug 2 by means of lentivirus infection and screening.Using CCK-8,colony formation,Transwell,as well as wound healing assays,we observed the changes of various biological behaviors of HCC cells after the level of uc002 yug.2 was altered.The overexpression of uc002 yug.2 could promote the proliferation,migration and invasion of HCC cells,and vice versa.Finally,by injecting HCC cells in the flank region of male BALB/c nu/nu mice,we found that the ability of HCC cells to form tumors decreased when the endogenous uc002 yug.2 was reduced.In addition,to explore the underlying mechanism through which uc002 yug.2 promote HCC,we detected the expression of RUNX1,which is a neighboring gene of uc002 yug.2,as well as RUNX3,which is also the RUNT-related gene family member,and had been reported to be downregulated in HCC.The results showed that expression of RUNX1 can be negatively regulated by uc002 yug.2 without affecting the RUNX3 level.Since RUNX1 is reported to play a role as cancer-suppressor,we speculate that the effect of uc002 yug.2 on HCC may have been achieved by downregulating RUNX1.In addition,in order to explore the significance of lnc RNA as a molecular marker of cancers,we also conducted a meta-analysis of lnc RNA Urotical carcinoma-associated 1(UCA1),which has been studied in various cancers.UCA1 has been reported to be overexpressed and correlated with progression in various cancers.However,the association between UCA1 expression and some clinicopathological features of digestive system malignancies,such as metastasis and survival,remains inconclusive.Therefore,a meta-analysis was performed to investigate the clinical significance of UCA1 in digestive system malignancies.Relevant literatures were searched in Pub Med,Web of Science,Cochrane Library and Embase databases updated to May 2016.A total of 1089 patients from 10 studies were included in this meta-analysis.Meta-analysis results showed that digestive system malignancy patients with UCA1 overexpression were significantly more susceptible to develop lymph node metastasis(LNM)(OR = 1.85,95% CI: 1.28-2.67),distant metastasis(DM)(OR = 3.14,95% CI: 1.77-5.58)and suffer from poor overall survival(OS)(HR = 2.31,95% CI: 1.89-2.82,univariate analysis;HR = 2.24,95% CI: 1.69-2.98,multivariate analysis)and poor disease-free survival(DFS)(HR = 2.65,95% CI: 1.59-4.43,univariate analysis;HR = 2.50,95% CI: 1.62-3.86,multivariate analysis).In conclusion,this paper had studied the role and mechanism of lnc RNA in HCC and the significance of lnc RNA to predict the outcome of cancers.First,the relationship between uc002 yug 2 and HCC was investigated in tissue,cell,molecular levels,both in vivo and in vitro.In addition,through a meta-analysis of available data,UCA1 overexpression was found to be correlated with LNM,DM,poor OS and poor DFS.UCA1 may serve as an indicator for metastasis and poor prognosis in digestive system malignancies.These results above provide a theoretical basis for the development of tumor diagnosis and treatment methods targeting lnc RNA,as well as the identification of molecular markers for monitering progression of cancers.