MicroRNA-196a overexpression promotes cell proliferation and inhibits cell apoptosis through PTEN/Akt/FOXO1 pathway
| Autor: | Yong, Shang, Li-Qing, Wang, Quan-Yi, Guo, Tu-Long, Shi |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Osteosarcoma
Forkhead Box Protein O1 Reverse Transcriptase Polymerase Chain Reaction PTEN Phosphohydrolase Apoptosis Bone Neoplasms Cell Cycle Proteins Forkhead Transcription Factors Real-Time Polymerase Chain Reaction Transfection Up-Regulation Gene Expression Regulation Neoplastic MicroRNAs Cell Line Tumor Humans Original Article Phosphatidylinositol 3-Kinase Phosphorylation Apoptosis Regulatory Proteins Proto-Oncogene Proteins c-akt Cell Proliferation Signal Transduction |
| Zdroj: | International journal of clinical and experimental pathology. 8(3) |
| ISSN: | 1936-2625 |
| Popis: | MicroRNAs (miRNAs) are endogenous, non-coding, small RNAs, which play a critical role in regulating varieties of the biological and pathologic processes. MiR-196a has been reported to take part in tumorigenic progression of osteosarcoma (OS). However, the effects of miR-196a on OS are still unclear. The objective of this study is to investigate the molecular mechanism of miR-196a in osteosarcoma cells. In the present study, the expression of miR-196a in OS cell lines was detected by real-time PCR. We found that the expression level of miR-196a was markedly up-regulated in osteosarcoma cell lines compared with normal osteoblastic cells. Then, the miR-196a mimic was transiently transfected into MG63 and U2OS cells using Lipofectamine™ 2000 reagent. Subsequently, the MTT and Brdu-ELISA results showed that up-regulation of miR-196a promoted the cell viability and proliferation. Our results also showed that miR-196a mimic accelerated cell cycle progression of MG63 and U2OS cells by down regulation of p21 and p27, and upregulation of cyclin D1. In addition, overexpression of miR-196a suppressed apoptosis of MG63 and U2OS cells due to increasing BCL2L2 and MCL-1 expressions, and then inactivating caspase-3. Eventually, the effect of miR-196a mimic on the PTEN/phosphoinositide 3-kinase (PI3K)/Akt signaling pathway was explored by Western blot. From our results, transfection of miR-196a decreased the expression of PTEN and increased the phosphorylation of PI3K and Akt. Taken together, miR-196a should be an oncogene in osteosarcoma. The possible mechanism was that overexpression of miR-196a promoted proliferation of MG63 and U2OS cells by modulating the PTEN/PI3K/Akt signaling pathway. |
| Databáze: | OpenAIRE |
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