Clinical significance of miR-22 expression in patients with colorectal cancer

Abstract

MicroRNAs (miRNAs) are non-coding RNAs that have been shown to be aberrantly expressed in several tumor types. Of these miRNAs, miR-22 as tumor suppressor has been shown to play a crucial role in human carcinogenesis. However, its association with the clinicopathological features of colorectal cancer has yet to be addressed. In this study, we compared the expression of miR-22 between colorectal cancer tissues and the normal adjacent mucosa using a quantitative real-time RT-PCR. The association of miR-22 expression with clinicopathological characters was analyzed by appropriate statistical analysis. Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the associations of miR-22 expression with survival of patients. Results showed that the relative expression levels of miR-22 were significantly lower in colorectal cancer tissues than those in the normal adjacent mucosa, and low expression of miR-22 correlated with liver metastasis. Kaplan-Meier analysis indicated that patients with reduced miR-22 had a poor overall survival. Moreover, the multivariate analysis showed that reduced expression of miR-22 was an independent predictor of overall survival. Our data indicate the potential of miR-22 as a novel prognostic biomarker for CRC.

MicroRNA-22 Regulates Smooth Muscle Cell Differentiation From Stem Cells by Targeting Methyl CpG–Binding Protein 2

“…Several studies have independently identified miR-22 as a tumor suppressor. [15][16][17] Moreover, it has been recently reported that miR-22 could contribute to cardiac aging by inducing cellular senescence and promoting migratory activity of cardiac fibroblasts through targeting osteoglycin, 18 suggesting that miR-22 might play a role in cardiovascular disease. Furthermore, it has been documented that miR-22 is upregulated during human ES cell differentiation, 19 induced by TPA (12-O-tetradecanoylphorbol-13-acetate) during monocytic differentiation from HL-60 leukemia cell lines, 34 and is close associated with erythroid maturation, 35 implying that miR-22 could play a potential role in hematopoietic cell differentiation and maturation.…”

“…Although the disruption of miR processing during embryonic development provides important insights into the understanding of the functional involvements of miRs in cardiovascular development, manipulation of individual miRs may offer more precise answers to the significance and exact role of individual miRs in SMC differentiation because the elimination of virtually all miRs makes it impossible to identify relevant regulatory circuits and related miR targets. microRNA-22 (miR-22), has been originally suggested as tumor suppressor, [15][16][17] was found to play an important role in cardiovascular disease. It has been recently reported that miR-22 could contribute to cardiac aging by inducing cellular senescence and promoting migratory activity of cardiac fibroblasts trough targeting mimecan (osteoglycin).…”

Investigation of nonspecific cross-reacting antigen 2 as a prognostic biomarker in bone marrow plasma from colorectal cancer patients

“…At first glance, miR-21 shows great potential as a prognostic biomarker in CRC, but there are issues to address. First, several exploratory studies performed on CRC cohorts failed to identify miR-21 as a prognostic biomarker, but instead other miRNAs, such as miR-17, miR-18a, miR-133b, miR-185, miR-22, miR-200c , miR-141, miR-221 and miR-150 were associated with overall survival [168,169,176,[199][200][201] [202,203]. Secondly, miR-21 is not tissue specific, as it is found to be overexpressed in several cancers including breast, lung and kidney [204][205][206].…”

“…In addition, it is debatable whether colon taken adjacent from cancer can be denoted normal. Studies performed on normal colon alone to establish a baseline for miRNA expression are lacking and the few publications that show normal miRNA expression levels, relative to cancer, show great variation in expression of the individual miRNA [200,212]. In a study performed on CRC tissue samples where miRNA expression was reported to be upregulated in tumor tissue as opposed to normal adjacent tissue, a significant proportion of normal samples actually had higher expression levels than in tumor tissue: 33% for miR-15b, 37.5% for miR-191, 4% for miR-181b and 21% for miR-200c ( Figure 11) [169].…”

“…In our cohort miR-21 69 showed both high and varied expression, but we did not find any association with clinicopathological parameters or outcome. As with miR-31, there are discrepancies between studies on miR-21 expression among the ones that have found an association with outcome and the ones that have not [168,169,176,199,200]. What may cause the discrepancies is difficult to say whether they are caused by biological differences in the cohorts, sample size, normalization methods or other factors is only speculation at this time.…”