miR-27b-3p is Involved in Doxorubicin Resistance of Human Anaplastic Thyroid Cancer Cells via Targeting Peroxisome Proliferator-Activated Receptor Gamma

Autor:	Yi-Fan Han, Bing Ye, Yin-long Zhang, Yuan Xu, Shao-Jun Zhu, Jianda Dong, Jiong Chen
Rok vydání:	2018
Předmět:	0301 basic medicine Basic fibroblast growth factor Peroxisome proliferator-activated receptor Toxicology Real-Time Polymerase Chain Reaction Thyroid Carcinoma Anaplastic 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor microRNA polycyclic compounds medicine Humans Doxorubicin Luciferase Thyroid Neoplasms Anaplastic thyroid cancer Receptor Pharmacology chemistry.chemical_classification Antibiotics Antineoplastic technology industry and agriculture General Medicine medicine.disease Up-Regulation carbohydrates (lipids) PPAR gamma MicroRNAs 030104 developmental biology chemistry Cell culture Drug Resistance Neoplasm 030220 oncology & carcinogenesis Wetlands Cancer research medicine.drug
Zdroj:	Basicclinical pharmacologytoxicology. 123(6)
ISSN:	1742-7843
Popis:	Chemotherapy is one of the most effective forms of cancer treatment. It has been widely used in the treatment of various malignant tumours. To investigate molecular mechanisms responsible for the chemoresistance of anaplastic thyroid cancer (ATC), we established the doxorubicin (Dox) resistance of human ATC SW1736 and 8305C cells and named them SW1736/Dox and 8305C/Dox, respectively. We evaluated the expression of various micro-RNAs (miRNAs) between control and Dox-resistant ATC cells and found that the expression of miR-27b-3p was significantly increased in Dox-resistant ATC cells. Targeted inhibition of miR-27b can increase the sensitivity of SW1736/Dox and 8305C/Dox cells. Bioinformatics analysis revealed that miR-27b can directly target peroxisome proliferator-activated receptor gamma (PPARγ) within the 3' untranslated region (UTR). This was proved by the results that miR-27b-3p down-regulated the protein and mRNA levels of PPARγ. While the mutant in the core binding sites of PPARγ abolished miR-27b-3p-induced down-regulation of luciferase activity. Over-expression of PPARγ can increase the Dox sensitivity of SW1736/Dox and 8305C/Dox cells. Basic fibroblast growth factor (bFGF) might be involved in miR-27b-3p/PPARγ-regulated Dox resistance of ATC cells. The activation of p65 nuclear factor-κB (NF-κB) regulated the up-regulation of miR-27b-3p in Dox-resistant ATC cells. Collectively, our data revealed that miR-27b-3p/PPARγ is involved in the Dox resistance of human ATC cells. It suggested that targeted inhibition of miR-27b-3p might be helpful to overcome the drug resistance of ATC cells.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::cf4786a4b856de7ebb8c34e4e4a3da30 https://pubmed.ncbi.nlm.nih.gov/29924913 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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