The Function And Regulation Mechanisms Of LRG1 In The Tumorigenesis Of Colorectal Cancer

Aims: To investigate the plasma and tissue level of LRG1 in colorectal cancer(CRC)patients,and to detect the influence of LRG1 on the proliferation and apoptosis of colorectal cancer cells,therefore to explore the relationship between LRG1 and the tumorigenesis of CRCMethods: Enzyme-linked immunosorbent assay was used to measure the plasma level of LRG1 in the CRC patients.Real-time PCR and western blot were performed to evaluate LRG1 m RNA and protein expression in 60 cases of fresh CRC and matched normal tissues.SW480 and HCT116 cells were treated with si LRG1,si RUN1,si NC,or human recombinant LRG1.CCK-8 assays,cell cycle assays and apoptosis assays were performed to evaluate the proliferation and apoptosis of CRC cells.Cell cycle factors cyclin D1,cyclin B,cyclin E as well as apoptotic key genes Bcl-2,Bax and cleaved caspase-3 were detected by Real-time PCR and western blot.Results: The plasma level of LRG1 was significantly increased in CRC patients,while it was remarkably decreased in patients with resected colorectal cancers.In addition,both m RNA and protein levels of LRG1 were remarkable overexpressed in CRC tissues than normal tissues(P<0.001).The knockdown of LRG1 significantly inhibited cell proliferation,induced cell cycle arrest at the G0/G1 phase,and promoted apoptosis in SW480 and HCT116 cells in vitro.In addition,LRG1 silencing led to the downregulation of the levels of cyclin D1,B,and E and anti-apoptotic Bcl-2 while it up-regulated the expression of pro-apoptotic Bax and cleaved caspase-3.Furthermore,RUNX1 could be induced by LRG1 in a concentration-dependent manner,while the knockdown of RUNX1 blocked the promotion of the proliferation and inhibition of apoptosis induced by LRG1.Conclusions: The plasma and tissue level of LRG1 was significantly increased in CRC patients,and LRG1 plays a crucial role in the proliferation and apoptosis of CRC by regulating RUNX1 expression.Thus,LRG1 may be a potential detection biomarker as well as a marker for monitoring recurrence and therapeutic target for CRC.