Preliminary Study On The Role And Molecular Mechanism Of ASPH And L1CAM In The Development Of Colon Cancer

Colorectal cancer is a common gastrointestinal tumor,and it has a high incidence worldwide.At present,clinically early patients mainly rely on radical surgery,and for advanced patients generally rely on comprehensive treatment such as radiotherapy and chemotherapy,but each treatment has certain limitations.Therefore,it is necessary for us to further study the mechanism of the occurrence and development of colorectal cancer.It provides new molecular markers for the diagnosis of colorectal cancer,and also provides more choices and theoretical basis for the treatment of colorectal cancer.Aspartate β-hydroxylase(ASPH),a type 2 transmembrane protein in theα-ketoglutaracid-dependent dioxygenase family,has been shown to be highly expressed in various tumor tissues and almost not expressed in normal tissues.Using database analysis,we found that the expression of ASPH was high in colorectal cancer tissues,while low in normal colorectal tissues.The knockdown and overexpression of ASPH cell lines were constructed,and the role of ASPH in the development of colon cancer was studied by cell proliferation,colony formation,migration and apoptosis experiments.The knockdown and overexpression of ASPH cells were sent to complete transcriptome sequencing to explore the molecular mechanism of ASPH in the development of colon cancer.The results showed that ASPH could promote cell proliferation,colony formation,cell migration and inhibit cell apoptosis.It can also promote the development of colon cancer by inducing EMT to promote cell migration and affect the expression of IGFBP3,COL6A2 and other genes.Conclusion:ASPH is highly expressed in colorectal cancer tissues and low expressed in normal colorectal tissues.ASPH can promote the growth and metastasis of colon cancer by inducing EMT,affecting the expression of IGFBP3、COL6A2 and other genes.Therefore,ASPH is expected to become a molecular marker of colon cancer and a potential therapeutic target.L1 cell adhesion molecule(L1CAM)is highly expressed in colorectal cancer tissues,which can promote the growth and metastasis of colorectal cancer.Autophagy has a close relationship with tumors.In the early stage of tumors,autophagy plays an inhibitory role in tumors,but in the late stage of tumors,autophagy can promote the occurrence and development of tumors.The relationship between L1 CAM and autophagy has not been reported in the literature so far.We attempted to further reveal the mechanism of the occurrence and development of colorectal cancer by studying the relationship between L1 CAM and autophagy.In this study,by building a knockdown L1 CAM cell model,western blotting and laser confocal microscopy were used to detect the changes of autophagy induced by glucose starvation,and the effect of L1 CAM on p38 phosphorylation was also detected.The results showed that after knockdown of L1 CAM,autophagy was weakened and p38 phosphorylation was enhanced,while inhibition of p38 phosphorylation could restore the inhibitory effect of knockdown of L1 CAM on autophagy.Conclusion:L1 CAM can promote autophagy by inhibiting p38 phosphorylation.