The Role And Mechanism Research Of Pseudogene CTNNAP1 In Colorectal Cancer

Colorectal cancer is the world's third largest common malignant tumor and remains a major cause of cancer mortality in the world,largely due to its propensity to metastasize.There have been many comparative studies demonstrate that epigenetic changes closely associated with the occurrence and development of CRC.Although the achievements in colorectal cancer research are remarkable,its overall survival rate is still low.Therefore,a depth research to study colorectal cancer pathophysiology mechanisms of the disease is particularly important,and is expected to provide basic theory for the early diagnosis and treatment of colorectal cancer.Pseudogenes,is considered to be a new type of non-coding RNA,which sequence are similar to its protein-coding cognate gene sequence.These particular genes lose the ability to produce functional proteins,only act as a nonsense mutation or is the product of disabling mutations.Similar to other noncoding RNA,pseudogenes are also involved in many important biological processes and human diseases,especially cancer development.Up to now,there is growing evidence pseudogenes are widely involved in the body's physiological and pathological process.Pseudogenes act as competitive endogenous RNA(ceRNA)competitive combined the same mricoRNA with its cognate gene,in order to maintain its cognate gene expression.Accumulating evidence indicates that deregulation of cancer-associated pseudogene is involved in the pathogenesis of cancer.CTNNAP1,a processed pseudogene,showed 90% similarity to its cognate gene CTNNA1 at the nucleotide level.However,its biological function and underlying mechanism in cancer have remained elusive.Research method: 1,CTNNAP1 and CTNNA1 in clinical specimens and clinical pathologic correlation studiesIn the present study,we collected 56 CRC and paired adjacent non-tumor tissue samples and using reverse transcriptase polymerase chain reaction assay(RT-PCR),to detect the expression of pseudogenes CTNNAP1 and CTNNA1 expression in colorectal cancer.Aim to observe the relationship between the expression of CTNNAP1 and lymph node metastasis of the tumor and tumor staging of colorectal cancer.2,Functional experiment in vitro and phenotypic experiment in vivoThrough the CCK-8,colony formation and nude mouse tumorigenicity assay to study the overexpressed CTNNAP1 and CTNNA1 effect on tumor cell cycle.Using biological analysis and luciferase reporter gene experimental to analysis the relationships between CTNNAP1,pseudogenes CTNNA1 and miR-141.To explore the mechanism and the role of pseudogenes CTNNAP1 in regulating the expression of its cognate gene CTNNA1.Research results: In the present study,we demonstrated that CTNNAP1 was dysregulated in colorectal cancer and the degree of dysregulation was remarkably associated with tumor node metastasis(TNM)stage(P<0.05).Moreover,the mechanistic experiments revealed that pseudogene CTNNAP1 played a pivotal role in the regulation of its cognate gene CTNNA1 by competition for microRNA-141.Conclusion:Pseudogenes CTNNAP1 is a strong tumor suppressor,regulates CTNNA1-dependent cell growth by competing for miR-141 to participate in the pathogenesis of colorectal cancer.Pseudogenes CTNNAP1 act as competing endogenous RNA(ceRNA)via cross-talk between pseudogene CTNNAP1 and its cognate gene CTNNA1,this provides a new model of gene regulation for biology.These findings may light up a new regulatory circuit for exploring research underlying the pathogenesis of colorectal cancer and provide valuable markers to detect colorectal cancer.