lncRNAPVT1 targets miR-152 to enhance chemoresistance of osteosarcoma to gemcitabine through activating c-MET/PI3K/AKT pathway
| Autor: | Huan-Ye Zhu, Yuekui Jian, Zeyu Sun, Bo Li |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Antimetabolites Antineoplastic C-Met Cellular differentiation Cell Mice Nude Bone Neoplasms Deoxycytidine Pathology and Forensic Medicine Phosphatidylinositol 3-Kinases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor medicine Animals Humans MTT assay Viability assay Protein kinase B PI3K/AKT/mTOR pathway Mice Inbred BALB C Osteosarcoma Cell growth Chemistry Cell Biology Proto-Oncogene Proteins c-met Gemcitabine Gene Expression Regulation Neoplastic MicroRNAs 030104 developmental biology medicine.anatomical_structure Drug Resistance Neoplasm 030220 oncology & carcinogenesis Cancer research Heterografts Female RNA Long Noncoding Proto-Oncogene Proteins c-akt Signal Transduction |
| Zdroj: | Pathology - Research and Practice. 215:555-563 |
| ISSN: | 0344-0338 |
| DOI: | 10.1016/j.prp.2018.12.013 |
| Popis: | Background: LncRNA PVT1 has been reported to be involved in a variety of biological processes, including cell proliferation, cell differentiation and cancer progression. However, the mechanism by which LncRNA PVT1 contributes to chemoresistance of osteosarcoma cell, has not been fully elucidated. Methods: We first generatedLncRNA PVT1-overexpressed MG63 cells and LncRNA PVT1 knockdown MG63/DOX cells. Then, we examined the effect of LncRNA PVT1 on cell viability and colony formation ability by MTT assay and soft agar assay, respectively. In addition, we performed flow cytometry analysis to detect apoptosis induced by GEM. Dual luciferase reporter assay and RIP were used to confirmed the interaction between LncRNA PVT1 and miR-152. Finally, we determined protein level of c-MET, p-PI3K, and p-AKT by westernblot. Results: LncRNA PVT1 overexpression promoted cell proliferation and exhibited the anti-apoptotic property in LncRNA PVT1-overexpressing MG63 cells treated with gemcitabine. While, LncRNA PVT1-depleted MG63/DOX cells treated with gemcitabine exhibited significant lower survival rate and high percentage of apoptosis. Next, we found that LncRNA PVT1 could target and downregulated the level of miR-152. Interestingly, miR-152 greatly rescued the biological outcomes of LncRNA PVT1 not only in MG63 but also in MG63/DOX cells. We observed that LncRNA PVT1 markedly induced PI3K/AKT pathway activation, which was abolished by miR-152 mimics overexpression. Finally, c-MET inhibitor was used to confirm the essential role of c-MET in LncRNA PVT1 and miR-152-regulated PI3K/AKT signaling. Conclusion: We showed thatlncRNA PVT1 played a contributory role in chemoresistance of osteosarcoma cells through c-MET/PI3K/AKT pathway activation, which was largely dependent on miR-152. Our findings advance our understanding of how lncRNA PVT1 promotes chemoresistance of osteosarcoma cells and facilitate development of novel strategies for treating osteosarcoma. |
| Databáze: | OpenAIRE |
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