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

Authors:
Publisher website
Google Scholar
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.
Funding Information
  • Erwin Schroedinger Scholarship of the Austrian Science Funds (J3389-B23)

This publication has 29 references indexed in Scilit: