CircEGFR Promotes The Proliferation And Migration Of Colorectal Cancer Cells Through The MiR-106a-5p/DDX5 Axis

Background and Purpose:Colorectal cancer is a disease of common sight and concern in recent years,both in China and worldwide,and its incidence and mortality rate have always ranked as the third most common oncological disease.Even though both mortality and incidence rates have decreased from 1930 to 2018,even so,the overall survival rate of colorectal cancer is still low,recurrence rate is also high,and the prognosis of patients has not improved significantly.When many patients are diagnosed with colorectal cancer,their disease is often already at an advanced stage,and have lost the opportunity for surgery.Furthermore,the current treatment is limited mainly to radical resection,but the postoperative recurrence rate is still very high.Therefore,it is urgent for us to conduct basic research from the perspective of diagnosis and find new biomarkers.Recently,an increasing number of studies have reported that dysregulated expression of circular RNA(circ RNA)has a critical role in the development of several cancers,including colorectal cancer(CRC).Circular RNA can not only affect the cell physiological process through exosome signal transduction,but also mediates tumorigenesis by affecting cellular infiltration in the immune microenvironment.Therefore,the study of circ RNAs is of great significance for us to explore the pathological process of disease development.However,the specific molecular mechanisms of how circ RNAs affect colorectal carcinogenesis remain largely unknown.In this study,the possibility of circEGFR as a diagnostic marker and therapeutic target for colorectal cancer is explored through bioinformatics methods,biochemical tests and cytological experiments.Materials and Methods:Here,after reviewing the literature,it was found that EGFR-derived circEGFR can influence the physiological processes of tumor disease but has been little studied in colorectal cancer.q RT-PCR validation in colorectal cancer tissues revealed that the expression level of circEGFR was significantly increased compared to its corresponding paracancerous non-tumor tissues,and then univariate and correlated survival prognostic analyses were performed,which led to the conclusion that high circEGFR expression levels were associated with the clinicopathological characteristics and poor prognosis of colorectal cancer patients.In addition,the cell lines for further experiments were detected for the differential expression of circEGFR.CCK-8,Colony formation,and transwell assays were performed to determine the cells migration and proliferation.Results:1.circEGFR expression in colorectal cancer tissues and correlation with prognosisThe expression level of circEGFR was found to be significantly increased in its corresponding non-tumor tissues compared to that in the colorectal cancer patients,and then univariate and correlated survival prognostic analyses were performed,which showed that high circEGFR expression levels were associated with clinicopathological characteristics and poor prognosis in colorectal cancer patients.2.circEGFR expression and colorectal cancer cell proliferation and migrationSubsequently,the upregulation of circEGFR expression level was observed to enhance the proliferation ability and migration of colorectal cancer cells at the cellular level.3.circEGFR functioned as a ce RNA to regulate DDX5 expression in colorectal cancerWe used bioinformatics to predict some possible targets interacting with circEGFR and found that mi R-106a-5p could serve as a binding target and compete for endogenous RNAs of circEGFR.Meanwhile,circEGFR binding to mi R-106a-5p could attenuate the inhibition effect of mi R-106a-5p on the translation process of DDX5.4.circEGFR regulated the expression of the DDX5 and the DDX5-mediated signaling pathway in colorectal cancerAfter in-depth study of the molecular mechanism of circEGFR,we found that the up-regulation of circEGFR enhanced the expression of DDX5,and the AKT signaling pathway was also activated,resulting in the up-regulation of p-AKT expression level.At the same time,correlation analysis found that there was a negative correlation between circEGFR and mi R-106a-5p,but a positive correlation with DDX5.5.DDX5 knockdown affected the circEGFR-induced colorectal cancer progressionAfter that,in the rescue experiments,we observed the changes of circEGFR and cellular phenotype by downregulating the expression of DDX5.The results showed that the proliferation and migration of DDX5-knockdown cell lines also decreased.Conclusion:Together,these findings suggest that circEGFR can promote the proliferation and migration of colorectal cancer cells through the mi R-106a-5p/DDX5/ AKT axis,which has certain implications for subsequent studies and may also be a potential diagnostic marker or therapeutic target for patients with colorectal cancer.