MiR‐96‐5p influences cellular growth and is associated with poor survival in colorectal cancer patients

Abstract

Expression of miR-96-5p is frequently altered in various types of cancer and the KRAS oncogene has been identified as one of its potential targets. However, the biological role of miR-96-5p expression in colorectal cancer (CRC) and its ability to predict the clinical course of patients have not been investigated yet. In this study, we explored miR-96-5p expression in 80 CRC patients and evaluated the impact on clinical outcome by Kaplan-Meier curves and multivariate Cox proportional models. In vitro miR-96-5p inhibition and overexpression were performed in CRC cells and the effects on cellular growth, anchorage-independent growth, apoptosis, and epithelial-mesenchymal transition (EMT)-related gene expression were explored. Low miR-96-5p expression levels in tumor tissue were associated with distant metastasis (P = 0.025) and multivariate Cox regression analysis identified low levels of miR-96-5p as an independent prognostic factor with respect to cancer-specific survival (hazard ratio = 1.78, 95%CI = 1.03-3.03, P < 0.038). In vitro overexpression of miR-96-5p led to a reduced cellular growth rate (P < 0.05), reduced colonies in soft agar (P < 0.05), corroborated by a decreased cyclin D1 and increased p27-CDKN1A expression (P < 0.05). Forced expression of miR-96-5p in CRC cells entailed no effects on apoptosis or EMT-related genes but decreased the expression levels of the KRAS oncogene (P < 0.05). Despite regulating KRAS expression, there was no significant association in miR-96-5p expression levels and response rates to EGFR-targeting agents. In conclusion, our data suggest that miR-96-5p influences cellular growth of CRC cells and low expression of miR-96-5p seems to be associated with poor clinical outcome in CRC patients.