Increasing evidence suggests that microRNAs are associated with many important biologic processes in carcinogenesis. Despite ample research revealing the dysregualtion of miR-486-5p in various cancers, little is known about the roles of miR-486-5p in colorectal carcinoma (CRC). In this study, we investigated the biological functions and molecular mechanisms of miR-486-5p in CRC growth and invasion, discussing the potential of using miR-486-5p as a biomarker for colorectal cancers. Our data revealed that miR-486-5p was significantly downregulated in CRC tissues compared with the paracancer tissue by quantitative real-time polymerase chain reaction and that miR-486-5p was downregulated to a greater extent in advanced stage cancer (stage III and IV) as compared to early stage cancer (stage I and II). Luciferase reporter assay verified that neuropilin-2 was a direct functional target of miR-486-5p in the CRC cells, and upregulation of miR-486-5p in CRC cells negatively correlated with the expression of neuropilin-2. Furthermore, overexpression of miR-486-5p inhibited the tumor growth and lymphangiogenesis in nude mice, which was reversed by overexpression of neuropilin-2. Taken together, our study suggested miR-486-5p might be a suppressor of CRC.

No abstract

Background: Alternative splicing (AS) is an important mechanism of regulating eukaryotic gene expression. Understanding the most common AS events in colorectal cancer (CRC) will help developing diagnostic, prognostic or therapeutic tools in CRC. Methods: Publicly available RNA-seq data of 28 pairs of CRC and normal tissues and 18 pairs of metastatic and normal tissues were used to identify AS events using PSI and DEXSeq methods. Result: The highly significant splicing events were used to search a database of The Cancer Genome Atlas (TCGA). We identified AS events in 9 genes in CRC (more inclusion of CLK1-E4, COL6A3-E6, CD44v8-10, alternative first exon regulation of ARHGEF9, CHEK1, HKDC1 and HNF4A) or metastasis (decrease of SERPINA1-E1a, CALD-E5b, E6). Except for CHEK1, all other 8 splicing events were confirmed by TCGA data with 382 CRC tumors and 51 normal controls. The combination of three splicing events was used to build a logistic regression model that can predict sample type (CRC or normal) with near perfect performance (AUC = 1). Two splicing events (COL6A3 and HKDC1) were found to be significantly associated with patient overall survival. The AS features of the 9 genes are highly consistent with previous reports and/or relevant to cancer biology. Conclusions: The significant association of higher expression of the COL6A3 E5-E6 junction and HKDC1 E1-E2 with better overall survival was firstly reported. This study might be of significant value in the future biomarker, prognosis marker and therapeutics development of CRC.