title: 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.affiliation: Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria.
authors.forename: Anna Lena
authors.initials: AL
authors.lastname: Ress
authors.affiliation: Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria.
authors.forename: Verena
authors.initials: V
authors.lastname: Stiegelbauer
authors.affiliation: Institute of Pathology, Medical University of Graz (MUG), Graz, Austria.
authors.forename: Elke
authors.initials: E
authors.lastname: Winter
authors.affiliation: Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria.
authors.forename: Daniela
authors.initials: D
authors.lastname: Schwarzenbacher
authors.affiliation: Institute of Physiology and Pathophysiology, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Tobias
authors.initials: T
authors.lastname: Kiesslich
authors.affiliation: Department of Pathology, General Hospital Graz West, Graz, Austria.
authors.forename: Sigurd
authors.initials: S
authors.lastname: Lax
authors.affiliation: Institute of Pathology, Medical University of Graz (MUG), Graz, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Jahn
authors.affiliation: Division of Hematology, Department of Internal Medicine, Medical University of Graz (MUG), Austria.
authors.forename: Alexander
authors.initials: A
authors.lastname: Deutsch
authors.affiliation: Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bauernhofer
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Hui
authors.initials: H
authors.lastname: Ling
authors.affiliation: Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria.
authors.forename: Hellmut
authors.initials: H
authors.lastname: Samonigg
authors.affiliation: Division of Oncology, Department of Internal Medicine, Medical University of Graz (MUG), Graz, Austria.
authors.forename: Armin
authors.initials: A
authors.lastname: Gerger
authors.affiliation: Institute of Pathology, Medical University of Graz (MUG), Graz, Austria.
authors.forename: Gerald
authors.initials: G
authors.lastname: Hoefler
authors.affiliation: Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas.
authors.forename: Martin
authors.initials: M
authors.lastname: Pichler
mesh_terms: D017209:Apoptosis / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D008875:Middle Aged; D011379:Prognosis; D016016:Proportional Hazards Models
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; C541492:MIRN96 microRNA, human; D035683:MicroRNAs; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: colorectal cancer; microRNAs; prognosis