miR-887-3p Inhibits the Progression of Colorectal Cancer via Downregulating DNMT1 Expression and Regulating P53 Expression

Colorectal cancer (crc) is the third most diagnosed cancer worldwide and the second leading cause of cancer-related deaths.Many researchers have reported that abnormal micro rnas (mi rs) were expressed in crc and participated in the occurrence and progression of crc.However, there are few reports of mi r-887-3p regulating crc development.In the current study, we investigated the abnormal expression of mi r-887-3p and also demonstrated its regulatory role and detailed molecular mechanism in crc.Initially, mi rna expression data were obtained from tcga-coad that consisted of 453 crc samples and 8 normal tissue samples.These were downloaded and analyzed to compare the expression level of mi r-887-3p in crc tissues to that in normal tissues.Moreover, 32 pairs of surgically resected crc tumors and para-cancer tissues from our hospital were collected.Quantitative real-time pcr (q rt-pcr) was performed to detect mi r-887-3p expression levels in crc tissues, para-cancer tissues, several crc cell lines, and an intestinal epithelial cell line.Following mi r-887-3p mimic transfection in colon cancer sw480 cell line, the regulatory roles of mi r-887-3p on cell proliferation, apoptosis, invasion, migration, and epithelial-mesenchymal transition (emt) were detected through cck-8, flow cytometry, transwell assay, and western blot.After potential targeting protein was predicted by bioinformatic websites, the luciferase reporter assay and western blot were used to confirm the target of mi r-887-3p.The targeting protein expressions were detected by western blot and q rt-pcr.The relationship between mi r-887-3p level and the effect of mi r-887-3p on p53 expression was evaluated by western blot and q rt-pcr.The effects of mi r-887-3p on crc cell growth in vivo by xenograft tumor experiments were investigated, and ki-67 in tumor tissue was determined by immunohistochemistry.Results.The coad data demonstrated that the expression levels of mi r-887-3p in crc clinical sample tissues and cell line cultures were remarkably lower than para-cancer normal tissues and ncm460 cells (normal colonic epithelial cell line).Functional experiments demonstrated that overexpression of mi r-887-3p in sw480 cells significantly reduced proliferation, migration, invasion, and emt, and promoted cancer cell apoptosis.Additionally, western blot, q rt-pcr, and luciferase reporter assays confirmed that dnmt1 was a downstream target of mi r-887-3p.Moreover, the blocking of dnmt1 by mi r-887-3p mimics also promoted p53 expression.Finally, overexpression of dnmt1 in sw480 cells could partially reverse the regulatory effect of mi r-887-3p mimics on crc cell development.From in vivo experiments, overexpression of mi r-887-3p could inhibit tumor growth in crc xenograft mice and reduce the ki-67 level.Conclusion.The micro rna mi r-887-3p is a potential biomarker of crc.It inhibited crc cell proliferation, invasion, and emt, and promoted cell apoptosis through targeting and downregulating dnmt1 and promoting p53 expression.Therefore, mi r-887-3p may be a good biomarker and therapeutic target for crc treatment.

Journal: Computational Intelligence and Neuroscience (2022)
Publication types: Research Article;