The Mechanism Of Hepatocyte Nuclear Factor 4A（HNF4A） In Colorectal Cancergenesis And Metastasis

Dysregulation of apoptosis caused by DNA damage is usually closely related to the occurrence of tumor.We preformed an irradiation screen with C.elegans and found that the nuclear hormone receptor 14（nhr-14）is involved in DNA damage-induced apoptosis.In order to determine the role of NHR14 homolog HNF4A（hepatocyte nuclear factor 4 alpha HNF4A）in tumorigenesis and progression.We analyzed of the TCGA database and found that the m RNA level of HNF4 A is abnormally expressed in tumors and is highest in colorectal cancer.To further verify this result,we tested colorectal cancer patient samples and found that 43 pairs had a significantly higher HNF4 A expression in tissues than the adjacent normal tissues in 58 pairs of normal and tumor tissues,which accounted for 73 % of the total.Colorectal cancer is the most common type of intestinal malignant tumors,and the abnormally high expression of HNF4 A may participate in and regulate the formation and metastasis of colorectal cancer tumor.Therefore,we constructed a stable colon cancer cell line overexpressing HNF4 A and performed RNA sequencing to explore the role of HNF4 A in colon cancer.The results showed that HNF4 A was involved in and regulated a variety of cancer-related signaling pathways,including Wnt/β-catenin,and affected the proliferation and tumor staging of colorectal cancer.These findings will benefit our understanding of the tumorigenesis and metastasis of colorectal cancer,and will provide strategy for the subsequent colorectal cancer treatment and diagnosis.