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.

• Authors: Anna Lena Ress, Verena Stiegelbauer, Elke Winter, Daniela Schwarzenbacher, Tobias Kiesslich, Sigurd Lax, Stefan Jahn, Alexander Deutsch, Thomas Bauernhofer, Hui Ling, Hellmut Samonigg, Armin Gerger, Gerald Hoefler, Martin Pichler
• Journal: Molecular carcinogenesis (Mol Carcinog) Vol. 54 Issue 11 Pg. 1442-50 (Nov 2015) ISSN: 1098-2744 [Electronic] United States
• PMID: 25256312 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 Wiley Periodicals, Inc.

Chemical References

• CDKN1A protein, human
• Cyclin-Dependent Kinase Inhibitor p21
• MIRN96 microRNA, human
• MicroRNAs
• Cyclin-Dependent Kinase Inhibitor p27

Topics

• Apoptosis (genetics)
• Cell Proliferation (genetics)
• Colorectal Neoplasms (genetics, mortality)
• Cyclin-Dependent Kinase Inhibitor p21 (genetics)
• Cyclin-Dependent Kinase Inhibitor p27 (genetics)
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Gene Expression Regulation, Neoplastic (genetics)
• Genes, ras (genetics)
• Humans
• Male
• MicroRNAs (genetics)
• Middle Aged
• Prognosis
• Proportional Hazards Models