| Liver cancer as the highest incidence of malignant tumor diseases in the clinic.This is because the malignant degree of hepatocellular carcinoma(HCC) is higher, at the same time, once the onset, progress fast,relatively short survival time, the rapid development of treatments for hepatocellular carcinoma(HCC), but significantly by treatment, there are still many patients died during the five years.The recent development of molecular targeted therapy because of its high efficiency and high specificity to attract people's attention gradually.A noncoding RNA transcription is the length of more than 200 nucleotides of long chain noncoding RNA(lncRNA), rather than coding RNA can be divided into 5 kinds of different types, is a gene location decision, the five categories including two-way lncRNA lncRNA inside, lncRNA between gene, gene,antisense lncRNA lncRNA, justice.By genome sequencing analysis, we found that the presence of large amounts of long chain in the human genome noncoding RNA, of which nearly 24000 or so from multiple genes involved in the related functions,mainlyincluding transcription activation,silence, transcription interference within the nuclear transport, X chromosome, the chromatin modification and so on many biological activities.Based on the research of the long chain noncoding RNA thorough development, a variety of diseases in the role of long chain noncoding RNA is more and more obvious, the early stages of mirnas has become the study hotspot, and again after this long chain noncoding RNA to research frontier.A large number of studies have shown that in development of tumor long chain noncoding RNA abnormal expression plays an important role.This is because in the early embryonic development process of long chain noncoding RNA is involved in regulating process, and so for tumor cellproliferation characteristics and the activation of multiple potential has obvious effect.In this paper, the main focus of research involves a long chain the function and role of non-coding RNA in tumor tissues, helps to find control tumor growth of the long chain of non-coding RNA.Liver cancer cells long chain noncoding RNA compared to normal liver cells, its expression spectrum change significantly, the main trend is raised and lowered, the trend is more common.These abnormal expression of long chain noncoding RNA may involve a number of biological processes, which mainly include protein translation, cell cycle,mRNA splicing,gene transcription,etc, and show that long chain noncoding RNA can be in the process of protein expression and modification after expressing function;And long chain noncoding RNA is involved in many important process signal to adjust,which mainly includes JAK-STAT,Notch,p53 and MAPK pathways.We first analyze clinical samples by using the method of Real-time PCR and cell samples,we confirmed that compared with the healthy tissue and normal cells,LincRNA-p21 expression level drastically cut in tumor tissues, the results suggest that LincRNA-p21 may inhibit the growth of liver cancer tissue.We acetylated histone and by analysis of liver tumor tissue LincRNA-the combination of p21 gene promoter,found that cancer of the liver tissue and liver cancer cell acetylation level of histone H3 compared to normal liver tissue and normal cells, express exist differences.Explains why LincRNA-p21 gene expression in normal liver tissue level is higher than liver cancer tissue.In order to verify the LincRNA-biological function of p21, we change by using the method of cell transfection LincRNA liver cancer cell SMMC-7721-p21 expression level.We build the expression LincRNA p21 SMMC-7721 cell lines, and at the RNA level proves that the tumor cells SMMC-7721 there has been a marked LincRNA-after transfection p21 expression level increased, at the same time analyzed the Notch signaling proteins Hes-1 and the expression of NICD,the results showed that compared with the normal tissue,express declined significantly, there is statistical significance(P<0.05).In order to further verify the Notch signaling pathway and the relationship between the EMT related protein expression level, we through the western blot detection EMT related protein E cadherin, Claudin 1,q: N-cadherin and expression level, compared with normal group, expression level decreased obviously.Next we construct LincRNA- by using the method of siRNA p21 inhibition of cell lines, we found that the HepG2 cells in the event of a LincRNA- p21 protein involved in inhibition of Notch signaling pathway after Hes- 1 and NICD expression level to carry on the analysis, we found that the western blot detection and Notch signaling proteins Hes-1 NICD expression compared to normal liver tissue, significantly higher expression.In the protein levels of EMT related protein E cadherin,Claudin 1, q: N- cadherin and the expression level of analysis, we found that the western blot detection EMT related protein E cadherin, Claudin1,q:N-cadherin and expression compared to normal liver tissue,significantly increase.Through DAPT to Notch signaling pathways can effectively inhibit liver cancer cells invade the migration process, we found that the inhibition of Notch signal after the occurrence of the expression of protein and NICD Hes- 1,the results showed that compared with the normal tissue, a significant reduction in the expression, EMT related protein E cadherin, Claudin 1, q: N- cadherin and the expression of a significant decline.Showed that inhibition of Notch signaling pathway will increase the occurrence of EMT, may enhance the invasive cancer of the liver.And activation of the Notch signal will cancel the LincRNA-p21 expression inhibition of liver cancer cell invasion and metastasis.After all experiment using Jagged1 cells, using Transwell cell invasion and metastasis,the experimental results show that the aggressivity obviously increase of tumor cells.In order to furtherclarify LincRNA- p21, Notch and the relationship between EMT, we observed through the inhibition of Notch signal to the LincRNA- p21 interference effects on liver cancer cell invasion and metastasis of,the results showed that inhibition of Notch signal will cancel LincRNA-p21 interference on liver cancer cell invasion and metastasis.However, we cannot use a DAPT processing cell, cell invasion and metastasis after Transwell tests, we found that the inhibition of cancel after the invasion of tumor cells significantly reduced.Liver cancer by nude mice model to analyze the LincRNA-p21 possible mechanism, we found that the nude mice infected with transfection pcDNA LincRNA-p21 plasmid of cell,the transfer of tumor tissue in the body is significantly reduced, prove LincRNA-ever p21 gene expression of liver tumor invasion and metastasis has obvious inhibitory effect,then proves that inhibiting LincRNA-p21 expression level will effectively promote the tumor invasion and metastasis.Taken together,our findings suggest that LincRNA- p21 new features,namely important regulating role in the tumor microenvironment.The research deepened further understanding of the mechanisms of liver metastasis, prompt should re-examine liver metastasis process,in the process of early invasive cancer of the liver cells EMT plays an important role, and in the process of liver cancer cells of distal engraftment Notch signal pathway plays an important role, that in the different stages of transfer tumour cells use different strategies to achieve its malignant spread.Because the LincRNA-p21 of liver cancer invasion-transfer cascade has inhibitory effect on early and late stages, hence LincRNA-p21 may be used as a effective transfer therapy targets and estimate the prognosis of patients with signs molecules, at the same time,the research results in the treatment of liver cancer prevention has high clinical value. |
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