Expression Of RNA Methylase In Colorectal Cancer

Background and ObjectiveColorectal cancer(CRC)is one of the most common cancers with high morbidity and mortality in the world.CRC is the third-leading cause of incidence and the fifth-leading cause of mortality in neoplastic diseases,and hundreds of thousands of people are diagnosed with CRC and died of CRC every year according the latest epidemiological survey results in China.Therefore,CRC takes a leading role in China's burden of disease.For the lower early diagnosis rate,most patients with CRC are in advanced stage when they are diagnosed,and for which the overall survival for patients with CRC in China is not good.Currently,it begins to accentuate precise and individualized treatment in treatment of cancers,and hence the traditional surgical treatment combined with intravenous drug chemotherapy obviously cannot meet the needs of multidimensional treatment of tumors.Therefore,it is of great significance to research the pathogenesis of colorectal cancer.RNA methylation belongs to epigenetics.N6-methyladenosine(m6A),a most common type of RNA chemical modification,refers to methylation modification occurring at the sixth N atom of adenine.m6 A is a dynamic and reversible process which requires the participation of several related enzymes,and the enzymes can be sorted in three groups according to their functions: Writermethylase,Eraser-demethylase and Reader-enzymes of recognizing m6 A.Recently,researches find that m6 A may play an important role in the development of tumors.Studies showed that the expression of MRTTL3 in glioblastoma,breast cancer,liver cancer and leukemia is abnormal.But there are few researches involve in m6 A in the studies about CRC,and the role of m6 A modification enzymes in the development of CRC is still unknown.One of the major frontiers of natural sciences today,bioinformatics is an discipline in storage,retrieve and analysis about biological data with the help of computer.It mainly focuses on genomics and proteomics,specifically,starting from nucleic acid and protein sequences,analyzing the structural and functional biological information expressed in the sequences.In this study,we use bioinformatics methods and select METTL3,the core enzyme of RNA methylation modification,as our research object.To provides a reference for the role and mechanism of METTL3 in the development of CRC by exploring the expression of METTL3 in CRC and adjacent cancer tissues,and analyzing the functions of genes co-expressed with METTL3.Methods: 1 Analyzing the expression of METTL3 in CRC with bioinformatics 1.1 Oncomine database was used to analyze the expression of METTL3 in tumor tissues and para-tumor tissues,and research the correlation between METTL3 expression and prognosis in patients with CRC.1.2 LinkedOmics database was used to find the co-expressed genes of METTL3.1.3 DAVID database was used to research the gene function enrichment analysis of METTL3.1.4 Above results were used to explore the possible signaling pathway of METTL3.2 Validating the METTL3 expression in CRC by RT-qPCR,Western Blot and immunohistochemistry(IHC)Results: 1 Significantly higher expression of METTL3 in tumor tissues was observed than that in para-tumor tissues(p<0.05),and this outcome was consistent with the results of RT-qPCR,Western Blot and IHC.But no significant difference was found in the expression of METTL3 and prognosis in patients with CRC.2 According to the co-expression result,568 genes were significantly related to the expression of METTL3,in which 504 genes were positively correlated and 64 genes was negatively corelated with METTL3 expression.3 In biological process(BP),according to the gene function enrichment analysis,genes that co-expressed with METTL3 mainly participated in cell division,DNA repair,chromosome binding;In cellular component(CC),genes mainly distributed in nucleus,cytoplasm and mitochondria;And in molecular function(MF),protein binding and ATP binding are main function.4 TMEM127(Transmembrane protein 127),a negative feedback signal to mammalian target of rapamycin(mTOR)signaling pathway,was negatively correlated with METTL3 expression,and it may affect CRC development through PI3K-Akt-mTOR pathway.Conclusion: 1 METTL3 was highly expressed in CRC.2 Expression of METTL3 was not an indicator for patients with CRC.3 METTL3 may exert its influence in CRC through PI3K-Akt-mTOR pathway.