Curcumol Inhibits The Invasion And Migration Of Colorectal Cancer Cell By Regulating Mi R-30a-5p/Hippo Pathway

Objective: To investigate the effect of curcumol on proliferation,invasion and migration of colorectal cancer(CRC)and the effect of curcumol on Hippo/EMT pathway,and to study the role of miR-30a-5p in inhibiting the proliferation,invasion and migration of colorectal cancer cells,so as to provide a theoretical basis for the treatment of metastatic colon cancer.Methods: 1.Real-time quantitative polymerase chain reaction(RT-q PCR)assay was used to detect the expression of miR-30a-5p in human colorectal cancer tissues and cells.2.MTT,Transwell,Scratch and Western blot assay were used to detect the effects of different concentrations of curcumol on the proliferation,invasion and migration in colorectal cancer HCT116 cells,and the expression of Hippo/EMT pathway related proteins with different concentrations of curcumol.3.The knockdown and over-expressed miR-30a-5p plasmid were constructed to treat colorectal cancer cells alone or in combination with curcumol(50 μg/m L).MTT,Transwell,Scratch and Western blot assay were used to detect the effect on the proliferation,invasion and migration ability of HCT116 cells and the expression of Hippo/EMT pathway-related proteins.4.BALB/c nude mice were used to establish HCT116 transplanted tumor model,and they were randomly divided into positive group and curcumol dose groups(40 mg/kg/day).All mice were killed after 21 days,and tumors were obtained.RT-q PCR assay was used to detect the expression of miR-30a-5p and the expression of Hippo/EMT pathway-related proteins.Results: 1.The expression of miR-30a-5p in human colorectal cancer tissues was lower than that in adjacent normal tissues,and the expression of miR-30a-5p in HCT116 cells was higher than that in SW480 and SW620 cells.2.Curcumol up-regulated the expression of miR-30a-5p,and inhibited the proliferation,invasion and migration of CRC cells in a concentration-dependent manner.3.Mi R-30a-5p mimics promoted the expression of E-cadherin,MST-1,LATS1 and p-YAP1 in HCT116 cells,while decreased the expression of YAP1,β-catenin and MMP2.Mi R-30a-5p-sp downregulated the expressions of E-cadherin,MST-1,LATS1 and p-YAP1,while upregulated the expressions of YAP1,β-catenin and MMP2.4.The expression of miR-30a-5p was up-regulated in HCT116 cells after transfection with miR-30a-5p mimics,and the inhibitory effect of curcumol on proliferation,invasion and migration of colorectal cancer cells was enhanced.After transfection with miR-30a-5p-sp,the expression of miR-30a-5p in HCT116 cells was down-regulated,and the inhibitory effect of curcumol on the proliferation,invasion and migration of colorectal cancer cells was weakened.5.Mi R-30a-5p mimics enhanced the inhibition effect of curcumol on Hippo/EMT pathway,promoted the expression of E-cadherin,MST-1,LATS1 and p-YAP1 in HCT116 cells,while decreased the expression of YAP1,β-catenin and MMP2.However,miR-30a-5p-sp reversed the inhibitory effect of curcumol on Hippo/EMT pathway.Conclusions: The expression of miR-30a-5p was low in colorectal cancer.Curcuminol inhibited the proliferation,invasion and migration of CRC HCT116 cells by up-regulating the expression of miR-30a-5p.Curcumol inhibits the proliferation,invasion and migration of CRC cells,which may be related to the Hippo/EMT pathway.Mi R-30a-5p affects the proliferation,invasion and migration of colorectal cancer cells by regulating the Hippo/EMT pathway.Mi R-30a-5p enhanced the effect of curcumol on the proliferation,invasion and migration of CRC cells and the Hippo/EMT pathway.The down-regulation of miR-30a-5p reversed the inhibitory effect of curcumol on the proliferation,invasion and migration of CRC cells,suggesting that miR-30a-5p could be a potential target of curcumol in the treatment of colorectal cancer,and curcumol inhibits the proliferation,invasion and migration of colorectal cancer cells by miR-30a-5p to regulate the Hippo/EMT pathway.