Mechanistic Investigation Of Epigenetic Upregulation Of TRIM11 In Colorectal Cancer

Objective:Colorectal cancer(CRC)is one of the deadliest cancers.This is mainly due to late diagnosis that is closely related to the lack of specific biomarkers.Nevertheless,recent studies have shown that alterations in the expression of some molecules can occur at early stages during the pathogenesis of CRC.Although tripartite motif 11(TRIM11)is known to be oncogenic in many types of cancers,its role in the development and progression of CRC remains to be fully understood.The aim of this study is: 1)to characterize the expression of TRIM11 in CRC and to define its relationship with clinicopathological characteristics of patients;and 2)to examine the epigenetic mechanisms responsible for regulation of TRIM11 expression in CRC.Methods:1)Analysis of existing publically available datasets to examine the relationship between TRIM11 expression and clinicopathological characteristics of patients.2)qPCR analysis of a cohort of colon cancer and paired adjacent /normal colon tissues to verify the relationship between TRIM11 expression and clinicopathological characteristics of patients.3)Identification of mi RNAs that potentially target TRIM11 mRNA by using of bioinformatics analysis and through introduction of anti-miRNA oligonucleotides and miRNA mimics to clarify the role of identified miRNA in regulation of TRIM11.4)Examination of the effects of inhibitors of histone acetylation and deacetylation enzymes to understand the role of histone modification in regulation of TRIM11 expression.Results:1)The expression of TRIM11 in colorectal cancer tissue compared with adjacent tissues/normal tissue was upregulation.2)Analysis of prognosis showed that CRC patients with higher TRIM11 expression had a poor overall survival(OS)compared with those with lower expression(P =0.0268).Correlation analysis showed that there were no relationship between TRIM11 expression and clinicopathological characteristics of CRC patients(P >0.05).3)Introduction of anti-miR-1 oligonucleotides in CRC cells increased the expression of TRIM11,but introduction of miR-1 mimics in CRC cells reduced the expression of TRIM11.This suggested that TRIM11 may be one of the target genes of miR-1 in CRC.miR-1 participated in the regulation of TRIM11 in CRC.4)The expression of TRIM11 in CRC cells was reduced after treatment with inhibitors of histone acetylation enzymes,curcumin or C646.Reversely,the expression of TRIM11 in CRC cells was increased after treatment with inhibitor of deacetylation enzyme,sodium butyrate.This suggested that histone modification played a role in regulation of TRIM11 expression in CRC.Conclusion:1)TRIM11 is upregulation in colorectal cancer and is a potential prognosis molecular marker of CRC.2)Increase of histone acetylation and decrease of mi R-1 are responsible for upregulation of TRIM11 expression in CRC.