LINC00265 Promotes Growth Of Colorectal Carcinoma Via Increasing Expression Of ZMIZ2

Colorectal cancer(CRC)is one of the three most common cancers in the world.Therefore,it is of great practical significance to study the molecular mechanism of the occurrence and development of colorectal cancer and provide a theoretical basis for the development of effective anticancer drugs.Long non-coding RNA(lncRNA)is a class of RNA transcripts that are longer than 200 nucleotides and do not encode proteins.LncRNAs are abnormally expressed in many tumors and have carcinogenic or anticancer functions,but their specific molecular mechanisms in the development of colorectal cancer remain to be further studied.In this study,bioinformatics screening showed that the copy number and gene expression level of LINC00265 were significantly increased in colorectal cancer,and the high expression of LINC00265 in CRC was associated with poor clinical prognosis.First,we established four colorectal cancer cell lines with stable LINC00265 knockdown,namely HCT116,SW480,RKO and DLD1,and then conducted MTT assay and subcutaneous tumorigenesis assay in nude mice.The results showed that inhibition of LINC00265 inhibited the malignant proliferation of colorectal cancer cells.By analyzing the relationship between LINC00265 and mRNA expression in CRC cases in TCGA database,we found that ZMIZ2 had the strongest positive correlation with LINC00265.We confirmed that knockdown of LINC00265 inhibited the expression of ZMIZ2 in colorectal cancer cell lines,and knockdown of LINC00265 and Dicer1 restored the expression level of ZMIZ2 protein and mRNA.In addition,immunoprecipitation experiment with AGO-2 antibody showed that four miRNAs were simultaneously targeting LINC00265 and ZMIZ2 mRNA3 ’UTR,and LINC00265 was competitively bound to four miRNAs to reduce the inhibition of miRNA binding to ZMIZ2 mRNA3’ UTR on their expression.The above results indicate that LINC00265,as a miRNA sponge,can increase the expression of ZMIZ2.Similarly,we established four stable ZMIZ2-knockdown cancer cell lines.MTT assay and subcutaneous tumorigenesis assay in nude mice showed that inhibition of ZMIZ2 inhibited malignant growth of colorectal cancer cells,overexpression of ZMIZ2 promoted malignant growth of colorectal cancer cells,and inhibition of LINC00265 and overexpression of ZMIZ2 restored cell proliferation.The above results indicate that LINC00265 plays an important role in promoting CRC tumor growth by regulating the expression of ZMIZ2.In addition,we analyzed the patient samples in the TCGA database and found that the expression of ZMIZ2 in colorectal cancer was up-regulated,which corresponded to poor clinical prognosis.In conclusion,knockdown of LINC00265 and ZMIZ2 in colorectal cancer cell lines can significantly inhibit cell growth and subcutaneous tumorigenesis,indicating that high expression of LINC00265 and ZMIZ2 can maintain malignant proliferation of colorectal cancer.Moreover,LINC00265,as a miRNA sponge,increases the expression of ZMIZ2 and mediates the malignant proliferation of colorectal cancer.These studies are helpful to reveal the molecular mechanism of long non-coding RNA promoting the development and progression of colorectal cancer.