The identification of novel genes involved in colorectal cancerogenesis is of high clinical relevance for early diagnosis, applying new therapeutic strategies and monitoring disease recurrence, in order to reduce disease incidence and mortality. Gene silencing through CpG island hypermethylation is a major epigenetic mechanism involved in cancer development. In our study, we aimed to identify and validate novel genes with a tumour specific DNA methylation profile in colorectal cancer. We performed a whole-genome methylation scan and identified several possible candidate genes that are hypermethylated in tumour in comparison to healthy colon mucosa. Using methylation-specific high-resolution melting analysis in a set consisting of 133 colorectal cancer samples, we were able to confirm an altered CpG site in TMEM25 in 69.2% (92/133) tumours analysed. Furthermore, the expression of TMEM25 was found to be significantly lower in tumour tissue. An inverse correlation between hypermethylation of TMEM25 and TMEM25 down-regulated expression was observed.Our results suggest that epigenetic down-regulation of TMEM25 is cancer-related; we thus suggest that TMEM25 hypermethylation might play a significant role in altering expression of this gene in colorectal cancer.

MicroRNAs (miRNAs) play an important role in various physiologic and developmental processes and in the initiation and progression of cancer. This class of small, non-coding RNAs critically regulate gene expression at the post-transcriptional level and evidence suggests that they may function as both oncogenes and tumor suppressors. Colorectal cancer (CRC) is a major healthcare concern worldwide and in order to reduce CRC related deaths, research is aimed into the search for some novel screening approaches. In this sense, miRNAs are rapidly emerging as a novel class of biomarkers, with good potential as diagnostic and therapeutic targets. This review summarizes the recent findings of the clinicopathological relevance that miRNAs have in CRC initiation, development, and progress, highlighting their potential diagnostic, prognostic, and therapeutic use in CRC, focusing on the group of microsatellite instable and the group of hypermethylated CRCs, as well as discussing future prospects.

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