MicroRNA in colorectal cancer: from benchtop to bedside

Abstract

Colon carcinogenesis represents a stepwise progression from benign polyps to invasive adenocarcinomas and distant metastasis. It is believed that these pathologic changes are contributed by aberrant activation or inactivation of protein-coding proto-oncogenes and tumor suppressor genes. However, recent discoveries in microRNA (miRNA) research have reshaped our understanding of the role of non-protein-coding genes in carcinogenesis. In this regard, a remarkable number of miRNAs exhibit differential expression in colon cancer tissues. These miRNAs alter cell proliferation, apoptosis and metastasis through their interactions with intracellular signaling networks. From a clinical perspective, polymorphisms within miRNA-binding sites are associated with the risk for colon cancer, whereas miRNAs isolated from feces or blood may serve as biomarkers for early diagnosis. Altered expression of miRNA or polymorphisms in miRNA-related genes have also been shown to correlate with patient survival or treatment outcome. With further insights into miRNA dysregulation in colon cancer and the advancement of RNA delivery technology, it is anticipated that novel miRNA-based therapeutics will emerge.

Influence of miRNA-106b and miRNA-135a on butyrate-regulated expression of p21 and Cyclin D2 in human colon adenoma cells

“…Lately, Hu et al (2011) as well as Humphreys et al (2013) showed that butyrate also influences miRNA expression in HCT116 and HT29 colon cancer cells, respectively. Therefore, it can act both via its function as HDI and by regulation of miRNA which are dysregulated in CRC (Bartley et al 2011;Schetter et al 2008;Slattery 2000;Wu et al 2011). In colon tumors for example, miRlet-7, miR-24, miR-34, miR-125 and miR-143 are downregulated, whereas miR-21, miR-135 and miR-106b are upregulated (Faber et al 2009;Wu et al 2011).…”

“…Therefore, it can act both via its function as HDI and by regulation of miRNA which are dysregulated in CRC (Bartley et al 2011;Schetter et al 2008;Slattery 2000;Wu et al 2011). In colon tumors for example, miRlet-7, miR-24, miR-34, miR-125 and miR-143 are downregulated, whereas miR-21, miR-135 and miR-106b are upregulated (Faber et al 2009;Wu et al 2011). The deregulation of these miRNAs may influence the development of colon cancer.…”

“…The expression of miR-106b was significantly reduced upon treatment with both HDIs butyrate and TSA, especially after 48 h. Several studies have shown that miR106b is overexpressed in colon cancer cells and that it has oncogenic potential (Hu et al 2011;Schetter et al 2008;Wu et al 2011). A validated target gene of miR-106b is the cell cycle regulator p21.…”

“…Depending on their downstream target genes, miRNAs can exert a function as tumor suppressor or promoter. The expression of miRNAs has also been identified to be dysregulated in colon cancer (Bartley et al 2011;Schetter et al 2008;Wu et al 2011). Another epigenetic mechanism of gene regulation is the modification of histones like (de)acetylation or (de)methylation which also plays a crucial role in colon cancer development (van Engeland et al 2011).…”

Advances in epigenetic biomarker research in colorectal cancer

“…Currently, 54 miRNAs have been identified that are regulated either up or down in CRC cells relative to nontumor cells (Table 3) [69,70] . Of these, miR-17, miR-20, miR-21, miR-31, miR-92a, miR-93, miR-183 and miR-203 were upregulated in CRC cells, while miR-30a, miR-30c, miR-133a, miR-143, miR-145 were downregulated.…”