Expression Of FXR1 In Colon Cancer And Its Effect On Proliferation And Invasion Of Colon Cancer Cell

Colon cancer(CRC)is a malignant tumor of the digestive tract that occurs in the colon,which the incidence rate is the third in gastrointestinal tumors.In recent years,the incidence and mortality of colon cancer have been on the rise in China,which has reached or surpassed the average level of western developed countries,and the morbidity population has gradually become younger.Fragile X-related gene 1(FXR1)is an RNA-binding protein whose high expression in plasma is associated with a poor clinical prognosis of CRC.However,the specific mechanism and role of FXR1 in CRC have not been clarified.Therefore,to further explore the role of FXR1 in the occurrence and development of CRC and clarify the relevant mechanisms will provide new ideas for the treatment of CRC.Objective: To analyze the correlation between FXR1 and the survival as well as the prognosis of colon cancer patients,determine the effects of FXR1 on the proliferation,invasion and tumorgenesis of colon cancer cells in vitro and in vivo,and explore related mechanisms.Methods: A total of 164 tissue specimens from CRC patients who underwent surgical resection in the Affiliated Hospital of Jiangnan University from 2006 to 2008 were collected,detailed clinic pathological parameters were recorded and followed up on time.The expression of FXR1 in CRC tissues was detected by immunohistochemistry and grouped according to the results.Univariate and multivariate analysis of clinical parameters was performed,and survival curves were drawn according to the follow-up results to explore the relationship between FXR1 expression and prognosis of patients with CRC.To determine the effect of FXR1 on the malignant biological behavior of CRC cells,the expression of FXR1 was downregulated in human colon cancer cell line HCT116.MTT assay and clone formation assay were used to detect the changes in cell proliferation and clonogenic ability,Transwell assay was used to detect the changes in cell invasion ability.Meanwhile,to explore whether the progress of FXR1 affecting CRC is related to EMT,the expression of EMT-related markers such as TGF-beta,N-Cad and E-Cad was detected by WesternBlot.Finally,established nude mouse xenograft model,observed tumor formation and detected the expression of EMT-related molecules in tumor tissue.Results: The expression level of FXR1 in CRC cancer tissues is higher than that of corresponding CRC adjacent tissues,especially in cancer tissues with distant metastasis.In clinical parameters,the occurrence of tumor differentiation and distant metastasis was significantly correlated with the expression of FXR1,and there was no significant difference with other indicators.Patients with higher FXR1 expression have shorter survival times and a higher risk of death.Down-regulation of FXR1 significantly inhibited the proliferation,invasion,clone formation ability as well as the tumorigenic ability of HCT16 cells in nude mice.Western Blot and immunohistochemical results showed that the expression of E-Cad in the tumor tissue of the interference group was significantly up-regulated,while the expression of N-Cad and TGF-?1 was significantly down-regulated.Conclusions: This study shows that:(1)Compared with the corresponding paracancerous tissues,the expression of FXR1 is higher in CRC cancer tissues with distant metastasis;(2)The high expression of FXR1 is positively correlated with the poor prognosis of CRC patients;(3)Down-regulation of FXR1 inhibited the malignant biological behavior of HCT116 cells;(4)FXR1 affects the malignant progression of colon cancer by regulating the EMT process of CRC.Therefore,inhibition of FXR1 may be a potential new therapeutic approach for CRC.