DDIT4 affects colorectal carcinogenesis through autophagy-related pathways
Objective To observe the expression of DNA damage-inducible transcript 4(DDIT4)in colorectal cancer(CRC)tissues and paracancerous tissues,and to explore the correlation with clinicopathologic features,prognosis and mechanism of action.Methods A complete CRC dataset was collected from The Cancer Genome Atlas(TCGA)database to compare the expression and prognostic correlation analyses of DDIT4 mRNA,and key genes were screened for functional enrichment analysis.100 cases in the observation group and 60 cases in the control group of paraffin specimens diagnosed with CRC in our hospital from May 2022 to May 2023 were collected,and the expression of tumor and paraneoplastic DDIT4 was detected by immunohistochemical staining and correlation analysis of clinicopathological features was performed.The human colon epithelial cell line was used as the control,and the CRC cell line was cultured,and the expression of DDIT4 mRNA was detected by RT-PCR,the expression of DDIT4 by gene intervention,and the expression of autophagy pathway-related proteins(mTOR,p-mTOR,Beclin1,P62)by Western blot.Results TCGA database data and immunohistochemistry results showed that DDIT4 expression was significantly increased in CRC(P＜0.001),which was correlated with patients'overall survival,depth of infiltration,tumor size,lymph node metastasis,DUKES staging and serum CEA level(P＜0.05).Silencing the DDIT4 gene resulted in a relative increase in p-mTOR/mTOR ratio and P62 and a relative decrease in Beclin1 downstream of the mTOR autophagy-related pathway(P＜0.05).Conclusion DDIT4 gene was significantly associated with the development and poor prognosis of CRC,and its mechanism may be related to the involvement of DDIT4 in regulating the mTOR signaling pathway to activate autophagy.
DNA damage-induced transcript 4autophagycolorectal cancerimmunohistochemistrypoor prognosis
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