PloS one, 2013-01, Vol.8 (1), p.e53906
2013
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- Autor(en) / Beteiligte
- Titel
- MicroRNA-221 induces cell survival and cisplatin resistance through PI3K/Akt pathway in human osteosarcoma
- Ist Teil von
- PloS one, 2013-01, Vol.8 (1), p.e53906
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2013
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- MicroRNAs are short regulatory RNAs that negatively modulate protein expression at a post-transcriptional and/or translational level and are deeply involved in the pathogenesis of several types of cancers. Specifically, microRNA-221 (miR-221) is overexpressed in many human cancers, wherein accumulating evidence indicates that it functions as an oncogene. However, the function of miR-221 in human osteosarcoma has not been totally elucidated. In the present study, the effects of miR-221 on osteosarcoma and the possible mechanism by which miR-221 affected the survival, apoptosis, and cisplatin resistance of osteosarcoma were investigated. Real-time quantitative PCR analysis revealed miR-221 was significantly upregulated in osteosarcoma cell lines than in osteoblasts. Both human osteosarcoma cell lines SOSP-9607 and MG63 were transfected with miR-221 mimic or inhibitor to regulate miR-221 expression. The effects of miR-221 were then assessed by cell viability, cell cycle analysis, apoptosis assay, and cisplatin resistance assay. In both cells, upregulation of miR-221 induced cell survival and cisplatin resistance and reduced cell apoptosis. In addition, knockdown of miR-221 inhibited cell growth and cisplatin resistance and induced cell apoptosis. Potential target genes of miR-221 were predicted using bioinformatics. Moreover, luciferase reporter assay and western blot confirmed that PTEN was a direct target of miR-221. Furthermore, introduction of PTEN cDNA lacking 3'-UTR or PI3K inhibitor LY294002 abrogated miR-221-induced cisplatin resistance. Finally, both miR-221 and PTEN expression levels in osteosarcoma samples were examined by using real-time quantitative PCR and immunohistochemistry. High miR-221 expression level and inverse correlation between miR-221 and PTEN levels were revealed in osteosarcoma tissues. These results for the first time demonstrate that upregulation of miR-221 induces the malignant phenotype of human osteosarcoma whereas knockdown of miR-221 reverses this phenotype, suggesting that miR-221 could be a potential target for osteosarcoma treatment.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0053906Titel-ID: cdi_plos_journals_1327799055
- Format
- –
- Schlagworte
- 1-Phosphatidylinositol 3-kinase, 3' Untranslated Regions, AKT protein, Analysis, Antineoplastic Agents - pharmacology, Apoptosis, Apoptosis - drug effects, Assaying, Bioaccumulation, Biocompatibility, Bioinformatics, Biology, Biotechnology, Bone cancer, Bone Neoplasms - genetics, Bone Neoplasms - metabolism, Bone Neoplasms - pathology, Bone surgery, Breast cancer, Cancer therapies, Cell cycle, Cell Cycle - drug effects, Cell growth, Cell Line, Tumor, Cell Proliferation - drug effects, Cell survival, Chemotherapy, Chromones - pharmacology, Cisplatin, Cisplatin - pharmacology, Drug Resistance, Neoplasm - drug effects, Drug Resistance, Neoplasm - genetics, Enzyme Inhibitors - pharmacology, Female, Gene expression, Gene Expression Regulation, Neoplastic - drug effects, Genes, Genes, Reporter, Genetic research, Humans, Immunohistochemistry, Inhibitors, Kinases, Liver cancer, Luciferase, Luciferases, Medicine, Metastasis, MicroRNA, MicroRNAs, MicroRNAs - antagonists & inhibitors, MicroRNAs - genetics, MicroRNAs - metabolism, miRNA, Morpholines - pharmacology, Oncology, Orthopedics, Osteoblasts, Osteosarcoma, Osteosarcoma - genetics, Osteosarcoma - metabolism, Osteosarcoma - pathology, Pathogenesis, Phosphatase, Phosphatidylinositol 3-Kinases - antagonists & inhibitors, Phosphatidylinositol 3-Kinases - genetics, Phosphatidylinositol 3-Kinases - metabolism, Post-transcription, Prostate, Proteins, Proto-Oncogene Proteins c-akt - genetics, Proto-Oncogene Proteins c-akt - metabolism, PTEN Phosphohydrolase - genetics, PTEN Phosphohydrolase - metabolism, PTEN protein, Real time, Retailing, Ribonucleic acid, RNA, Sarcoma, Signal Transduction - drug effects, Survival, Tissues, Transcription (Genetics)