Abstract: Objective To investigate potential roles of miR-125 and SMAD4 in lipopolysaccharide (LPS)-induced colorectal epithelial cells transformed to cancer cells. Methods Cell viability of HCoEpiCs cells exposed to LPS for 24 h was evaluated by CCK-8 assay.CyclinD1,c-myc,Bcl-2,miR-125,and SMAD4 were measured by q-PCR in LPS-induced colorectal epithelial cells malignant transformation.Plane cloning and soft agar colony formation assay were used to identify the result of malignant transformation.Synthetic miR-125 mimic and inhibitor were used to mediate the expression of miR-125 in the 40th passage of LPS-induced HCoEpiCs cells.The activity of miR-125 in the region of SMAD4 3′-UTR was detected by the double luciferase gene report. Results Cell viability was signifi- cantly repressed by 10 μg/mL LPS.The expression of miR-125 was increased in the 40^th passage of LPS-induced HCoEpiCs cells,but the level of SMAD4 was down-regulated.The level of SMAD4 and c-myc were decreased when miR-125 was over-expressed in HCoEpiCs cells.Meanwhile,compared to the control group,the activity of SMAD4 3′-UTR-wild was repressed by miR-125 mimic, but no significant change was observed in the 3′-UTR-mut cells. Conclusions LPS-induced colorectal epithelial cells might be inhibited to transform to cancer cells through miR-125 binding to SMAD4.

Key words: lipopolysaccharide, colorectal epithelial cells, cancer cell, miR-125, SMAD4