Effect Of PTEN On Cell Proliferation And Apoptosis Of Colon Cancer Mediated By MiR-5590 And MCRS1

Colon cancer originates from colon epithelium and is one of the most common malignant tumors of digestive tract.In recent years,the incidence rate of colon cancer in China has continued to increase.The occurrence and development of colon cancer is a complex process related to multiple genes and factors.Therefore,it is of great practical significance to clarify the molecular mechanism related to the pathogenesis of colon cancer,especially to develop more effective therapeutic drugs targeting colon cancer.Microspherule protein 1(MCRS1)exists in the nucleus and cytoplasm.It can not only play a role as a member of NSL acetyltransferase complex or INO80 chromatin remodeling complex,but also participate in the growth,invasion and metastasis of cancer cells independently of NSL and INO80 complex.However,it is still unclear how MCRS1 affects the invasion and metastasis of tumor cells and its molecular mechanism.Micro RNA(mi RNA)is a small non-coding RNA family,which negatively regulates the post-transcriptional level of target genes by recognizing the 3’-UTR homologous sequence of target m RNA.A large number of research data have shown that mi RNA is closely related to the occurrence and development of tumors.In cancer cells,mi RNA can play a role as a tumor suppressor or carcinogen according to the different targeted genes.The mi R-5590 mentioned in this paper has been reported to be involved in the pathogenesis of multiple malignant tumors,but its role in colorectal cancer and its molecular mechanism are poorly understood.Therefore,this paper intends to explore the antagonistic effect of MCRS1 and mir-5590 on colon cancer cells and the signal pathway regulated by them by studying the interaction between MCRS1 and mir-5590.The main work and results of this paper are as follows:1.Our research group has been doing research on NSL and INO80 complex for many years.As the shared subunit of these two complexes,MCRS1 may play an important role in cells.We used TCGA database to conduct TIMER analysis,and found that the expression of MCRS1 in colon cancer tissue was significantly increased,suggesting its correlation with tumorigenesis.This assumption has been verified in cell experiments.In many tumor cell lines,we found that the expression of MCRS1 in HCT116 colon cancer cells was higher than that in other tumor cells.At the same time,the colony formation and scratch test confirmed that overexpression of MCRS1 can promote the proliferation of HCT116 cells and the migration of SW480 cells,suggesting that MCRS1 is related to the pathogenesis of colon cancer;2.In order to further explore the signal pathway related to the effect of MCRS1 on colon cancer cells,we detected several key proteins related to tumor-related pathways after overexpression of MCRS1 in HCT116 cells.The results showed that MCRS1 increased the level of phosphorylated AKT by inhibiting PTENactivated AKT signal pathway,and decreased the expression level of apoptotic factor Bax,suggesting that MCRS1 may mediate PTEN-AKT signal pathway to participate in the regulation of the pathogenesis of colon cancer.According to existing research reports,many non-coding mi RNAs in cells participate in the regulation of AKT signaling pathway.We selected several mi RNAs closely related to tumorigenesis and screened the genes that may be regulated by these mi RNAs using Target Scan website.We found that the candidate genes for targeted regulation of mi R-5590 include PTEN,AKT,Bax,NSL1(subunit of NSL complex)and YY1(subunit of INO80 complex),etc,suggesting that mi R-5590 may also participate in the regulation of PTEN-AKT signal pathway like MCRS1.Our experimental results confirmed that in HCT116 cells,mi R-5590 targeted PTEN,and by binding with the 3 ’-UTR region of PTEN,after transcription,inhibited the m RNA and translated protein levels of PTEN,thereby activating the AKT pathway and reducing the expression level of apoptotic factor Bax.In addition,the results of colony formation and scratch test showed that the expression of simulated mi R-5590 can promote the proliferation and migration of colon cancer cells,suggesting that MCSR1 and mi R-5590 participate in the regulation of the same signal pathway,and may coregulate the pathogenesis of colon cancer;3.In order to determine whether MCRS1 and mi R-5590 co-participate in the regulation of the pathogenesis of colon cancer,we detected AKT pathway protein after co-transfection of MCRS1 and mi R-5590 in HCT116 cells,and carried out colony formation and Hoechest staining experiments.The results showed that compared with single transfection of MCRS1 or mi R-5590,the cotransfection of MCRS1 and mi R-5509 had stronger inhibition on PTEN,and more obvious effect on the proliferation and apoptosis of colon cancer cells,It is suggested that MCRS1 and mi R-5590 are involved in the regulation of the pathogenesis of colon cancer.These results suggest that MCRS1 and mi R-5590 co-mediate PTEN to participate in the regulation of AKT pathway,thereby affecting the proliferation and migration of colon cancer cells.Our results will provide new theoretical basis and therapeutic strategy for the pathogenesis of colon cancer.mi R-5590/MCRS1 may be a new therapeutic target for colon cancer.