Prognostic Significance of miR-215 in Colon Cancer

Abstract

The clinical utility of miR-215 as a potential biomarker in colon cancer was investigated. The levels of miR-215 were quantified by real-time qRT-PCR in 34 paired normal and tumor specimens. The expression levels of miR-215 were decreased in colon tumors, and were associated with patient survival. Thus, miR-215 is a potential prognostic biomarker in colon cancer. Background We have previously shown that miR-215 suppressed the expression of key targets such as thymidylate synthase (TS), dihydrofolate reductase, and denticleless protein homolog (DTL) in colon cancer. miR-215 is a tumor suppressor candidate due to the upregulation of p53 and p21 by targeting DTL. However, high levels of miR-215 conferred chemoresistance due to cell cycle arrest and reduced cell proliferation by suppressing DTL. In this study, the clinical significance of miR-215 was further investigated as a potential prognostic biomarker in colon cancer patients. Methods Total RNAs were extracted from 34 paired normal and colon (stage II and III) tumor specimens using the Trizol-based approach. The levels of miR-215 and a closely related miR-192 were quantified using quantitative real-time polymerase chain reaction (qRT-PCR) expression analysis. The expression of DTL mRNA and protein were quantified by real time qRT-PCR and immunohistochemistry. Results The expression levels of miR-192 (P = .0008) and miR-215 (P < .0001) were significantly decreased in colon tumors compared with normal tissues. DTL was significantly over-expressed and was inversely correlated with miR-215, further suggesting an in vivo physiologic relevance of miR-215 mediated DTL suppression. Kaplan-Meier survival analysis by Cox regression revealed that high levels of miR-215 expression (hazard ratio, 3.516; 95% confidence interval, 1.007–12.28, P = .025) are closely associated with poor patient’s overall survival. Furthermore, an elevated expression of a miR-215 target protein DTL was detected in colon cancer tissues whereas no expression was present in normal tissues. Conclusion miR-215 has a unique potential as a prognostic biomarker in stage II and III colon cancer.

MicroRNA-215 functions as a tumor suppressor and directly targets ZEB2 in human pancreatic cancer

“…Recent studies confirmed miR-215 downregulation in esophageal adenocarcinoma (Wijnhoven et al, 2010), colon cancer (Karaayvaz et al, 2011), and RCC (White et al, 2011). Decreased miR-215 levels in colorectal cancer were associated with increased tumor sizes and shorter disease-free survival after radical surgery (Chiang et al, 2012;Li et al, 2013).…”

“…miR-215 is upregulated in cervical cancer , hepatocellular carcinoma , gastric cancer (Deng et al, 2014), and prostate cancer (Walter et al, 2013), and it acts as a potential oncogene in these tumors. On the contrary, the expression of miR-215 was found to be significantly decreased in esophageal adenocarcinoma (Wijnhoven et al, 2010), colon cancer (Karaayvaz et al, 2011), and renal cell carcinoma (RCC) (White et al, 2011), where it acts as a candidate tumor suppressor. However, the correlation between miR-215 dysregulation and clinicopathological characteristics of pancreatic cancer has not yet been evaluated, and the biological roles of miR-215 and its direct functional targets in pancreatic cancer remain poorly understood.…”

MicroRNA-215 acts as a tumor suppressor in breast cancer by targeting AKT serine/threonine kinase 1

“…The expression level of miR-215 was demonstrated to be associated with the International Federation of Gynecology and Obstetrics stage, the histological grade, and the extents of vascular invasion and lymph node metastasis of cervical cancer; the 5-year survival rate was lower in patients with stage II cervical cancer who exhibited miR-215 overexpression (29). However, previous studies have also demonstrated that miR-215 may be downregulated in epithelial ovarian (30), pancreatic (31), non-small cell lung (32), breast (33) and colon (34) cancer. In the study on pancreatic cancer, a low expression level of miR-215 was significantly associated with a large tumor size, an advanced TNM stage, a high extent of lymph node metastasis and vessel invasion, and lower overall survival time; multivariate regression analysis demonstrated that miR-215 underexpression was an independent unfavorable prognostic factor for patients (31).…”

Associations between Markers of Colorectal Cancer Stem Cells, Mutations, Mirna, and Clinical Characteristics of Ulcerative Colitis

“…Although the cause of this discrepancy is unclear, we reason that miR-215 may act as a double-edged sword, modulating multiple targets and pathways. Karaayvaz et al reported that a high level of miR-215 suppresses tumor cell proliferation and increases cell cycle arrest [42]. The differential expression of miR-215 is reflected by the stage of transformation, dysplasia versus carcinoma.…”