Study On The Role Of LncRNAp26302 In Hepatocellular Carcinoma And Its Regulatory Mechanism

ObjectivesLncRNA is a class of RNA molecules with a length greater than 200 bases.Unlike mRNA,tRNA and rRNA,which itself can not encode proteins and are not directly involved in protein synthesis,lack of complete open reading frames,Protein coding ability of RNA,its content is much higher than the protein encoding the protein.LncRNA was thought to be the "noise" of the genomic transcription at the time of the discovery,and did not have any biological function,but its function was gaining attention with the application of high-throughput chips.The gene background of these RNA molecules is complex and can be a sequence consisting of a promoter,a gene intron,an enhancer initiation sequence,an antisense strand of RNA,a sequence between genes,and the like.LncRNA regulatory gene expression is mainly through the epigenetic regulation,transcriptional regulation,post-transcriptional regulation of three ways to complete.The regulation of epigenetic genetics is most important,involving DNA methylation,changes in nuclear body position,mi RNA expression abnormalities,histone acetylation,chromatin remodeling and so on.Hepatocellular Carcinoma(HCC)is a common disease in globalmalignancies,ranking sixth,and the mortality rate is third,about 700,000 people die each year from liver cancer with a mortality rate of 93%.HCC metastases are mainly blood metastasis,lymphatic metastasis,the invasion of nearby organs.At present,the preferred treatment is still the main surgical resection,although the treatment of liver cancer technology continues to improve,such as liver transplantation,radiotherapy,particle implantation,chemotherapy and so on.The overall 5-year survival rate of patients with hepatocellular carcinoma has not been significantly improved,and the overall 5-year survival rate after treatment is less than 12%.Studies have shown that LncRNA is closely related to the molecular mechanism and action of apoptosis,cell cycle,tumor metastasis,autophagy,chemotherapy resistance,prognosis and epigenetic regulation.Some LncRNAs play an important role in oncogenes,tumor suppressor genes,and even at the same time play oncogene and tumor suppressor genes.LncRNA plays a potentially important role in all aspects of tumor development and development.Therefore,LncRNA has become one of the hotspots in tumor research.Compared with the study of miRNA,the study of LncRNA is developing rapidly.Several LncRNAs associated with hepatocellular carcinoma are found in HCC-related studies.Most LncRNA molecules are not well defined,and LncRNA is expressed abnormally with hepatocellular carcinoma.It is still necessary to explore its function.The aim of this study was to analyze the expression profile of LncRNA in human hepatocellular carcinoma and adjacent tissues,so as to better understand the role of LncRNA in the development and metastasis of HCC.MethodsThe expression of LncRNA and mRNA in 14 hepatocellular carcinomatissues and paracancerous tissues were detected by using jingxin which have40916 LncRNAs and 34235 mRNAs.The expression of LncRNA and mRNA was detected by Agilent Technologies Extraction(v10.7)Software to analyze the hybrid image and extract the data.The data were then normalized and analyzed using Agilent GeneSpring software.(P2070_ENST00000432120,p2959_ENST00000534150,p5208_ENST00000560278,p26302_uc003lzi,p33425_ENST00000559280,p33594_ENST00000447271,p33758_uc021qrb)were used to analyze the expression of LncRNA and mRNA co-expression network and related RNA molecule target genes.Real-time quantitative PCR was used to validate the expression of these genes in hepatocarcinoma cell lines and normal hepatocytes,as well as the random selection of 5 pairs of HCC tissues and adjacent tissues.LncRNAp26302 was selected as the research target,and the interaction between its biological cytology and target gene was studied.Results1,A total of 1706 LncRNA were found to be differentially expressed,accounting for 4.17% of all LncRNA,of which 2 fold more than 609 LncRNA at the same time,more than 2 times a total of 1097 LncRNA at the same time down.We used the biodegradation of these differences LncRNA more than 2times,the target gene GO enrichment and KEGG pathway analysis,and found that some of the differentially expressed LncRNA involved in epigenetic regulation is most important,involving DNA methylation,nucleosomes Localization,miRNA expression abnormality,histone acetylation,chromatin remodeling,etc.,may also be involved in MAPK,P53,PDGF,Notch,JAK-STAT,Wnt and other signal pathway regulation.2,Silencing LncRNAp26302 can inhibit the proliferation,invasion and migration ofhepatocarcinoma cells,which can lead to G/M arrest of hepatocarcinoma cells,which can promote the apoptosis of hepatocellular carcinoma cells.The mechanism may play an important role in the activation of mitochondrial apoptosis pathway and upregulate the ratio of Bax/Bcl-2?3.PLK1 may be the target gene of LncRNAp26302?Silent LncRNAp26302 may up-regulates wee1 expression and inhibits CyclinB1 / CDK1 expression and regulates the phosphorylation of JNK,ERK and P38 protein in MAPK pathway,Inhibit the activation of Akt in PI3 K / Akt pathway,inhibit the anti-apoptotic effect of XIAP,and play a role in inhibiting the proliferation and promoting the apoptosis of hepatocarcinoma cells.Conclusion1.The differential expression profile of LncRNA in hepatocellular carcinoma tissues and adjacent tissues of Guangxi population was established,and the co-expression network of LncRNA and mRNA and the target gene prediction of related RNA molecules were constructed.2.The proliferation,invasion and migration of LncRNAp26302 cells in hepatocarcinoma cells decreased,the cell cycle was arrested in G2 / M phase,and the apoptosis rate was significantly increased,suggesting that LncRNAp26302 may be involved in regulating the development and metastasis of hepatocellular carcinoma.3.LncRNAp26302 may be involved in the occurrence,development and migration of hepatocellular carcinoma through target signal PLK1 via MAPK signal pathway,PI3 K / AKT signal pathway and other signal pathways.