Skip to Content
Merck
  • MicroRNA-17-5p promotes chemotherapeutic drug resistance and tumour metastasis of colorectal cancer by repressing PTEN expression.

MicroRNA-17-5p promotes chemotherapeutic drug resistance and tumour metastasis of colorectal cancer by repressing PTEN expression.

Oncotarget (2014-06-11)
Lekun Fang, Haoran Li, Lei Wang, Jun Hu, Tianru Jin, Jianping Wang, Burton B Yang
ABSTRACT

Colorectal cancer (CRC) is one of the most common cancers worldwide, especially in Western countries. Although chemotherapy is used as an adjuvant or as a palliative treatment, drug resistance poses a great challenge. This study intended to identify biomarkers as predictive factors for chemotherapy. By microarray analysis, we studied miRNAs expression profiles in CRC patient, comparing chemoresistant and chemosensitive groups. The miRNAs of interest were validated and the impact on clinical outcomes was assessed in a cohort of 295 patients. To search for potential targets of these miRNAs, tissue samples were subject to in situ hybridization and immunohistochemistry analysis. Colorectal adenocarcinoma cells were also used for in vitro experimentation, where cellular invasiveness and drug resistance were examined in miRNA-transfected cells. The expression level of miRNA-17-5p was found increased in chemoresistant patients. Significantly higher expression levels of miR-17-5p were found in CRC patients with distant metastases and higher clinical stages. Kaplan-Meier analysis showed that CRC patients with higher levels of miR-17-5p had reduced survival, especially in patients who had previously received chemotherapy. Overexpression of miR-17-5p promoted COLO205 cell invasiveness. We found that PTEN was a target of miR-17-5p in the colon cancer cells, and their context-specific interactions were responsible for multiple drug-resistance. Chemotherapy was found to increase the expression levels of miR-17-5p, which further repressed PTEN levels, contributing to the development of chemo-resistance. MiR-17-5p is a predictive factor for chemotherapy response and a prognostic factor for overall survival in CRC, which is due to its regulation of PTEN expression.

MATERIALS
Product Number
Brand
Product Description

Sodium laurilsulfate, European Pharmacopoeia (EP) Reference Standard
Sigma-Aldrich
Mitomycin C from Streptomyces caespitosus, ≥98% (HPLC), potency: ≥970 μg per mg (USP XXIV), γ-irradiated, suitable for cell culture
Supelco
Sodium dodecyl sulfate, dust-free pellets, suitable for electrophoresis, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate solution, BioUltra, for molecular biology, 20% in H2O
Sigma-Aldrich
Sodium dodecyl sulfate solution, BioUltra, for molecular biology, 10% in H2O
Sigma-Aldrich
Propidium iodide solution
Sigma-Aldrich
Mitomycin C from Streptomyces caespitosus, powder, contains NaCl as solubilizer
Sigma-Aldrich
Propidium iodide, ≥94.0% (HPLC)
Sigma-Aldrich
Sodium dodecyl sulfate, ReagentPlus®, ≥98.5% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, BioReagent, suitable for electrophoresis, for molecular biology, ≥98.5% (GC)
Sigma-Aldrich
Mitomycin C from Streptomyces caespitosus, powder, BioReagent, suitable for cell culture
Sigma-Aldrich
Propidium iodide, ≥94% (HPLC)
Sigma-Aldrich
Sodium dodecyl sulfate, BioUltra, for molecular biology, ≥99.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, tested according to NF, mixture of sodium alkyl sulfates consisting mainly of sodium dodecyl sulfate
Sigma-Aldrich
Mitomycin C from Streptomyces caespitosus, ≥970 μg/mg (USP XXIV)
Supelco
Sodium dodecyl sulfate, suitable for ion pair chromatography, LiChropur, ≥99.0%
Sigma-Aldrich
Sodium dodecyl sulfate, ≥98.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, ≥90% ((Assay))
Sigma-Aldrich
Sodium dodecyl sulfate, ≥99.0% (GC), dust-free pellets
Sigma-Aldrich
Sodium dodecyl sulfate, ACS reagent, ≥99.0%
Sigma-Aldrich
Sodium dodecyl sulfate, BioXtra, ≥99.0% (GC)
Sigma-Aldrich
Sodium dodecyl sulfate, 92.5-100.5% based on total alkyl sulfate content basis
Sigma-Aldrich
Sodium dodecyl sulfate, BioReagent, suitable for electrophoresis, for molecular biology, ≥98.5% (GC), free-flowing, Redi-Dri