10 March 2020 : Clinical Research
Downregulated Long Non-Coding RNA MSC-AS1 Inhibits Osteosarcoma Progression and Increases Sensitivity to Cisplatin by Binding to MicroRNA-142Longqiang Zhang1ACDF, Guangzong Zhao1ABDF, Shaolin Ji1CD, Qihua Yuan1DEF, Haiyan Zhou2F*
Med Sci Monit 2020; 26:e921594
BACKGROUND: Osteosarcoma (OS) is the most prevalent malignant primary bone tumor, resulting from severe transformation of primitive mesenchymal cells, which induces osteogenesis. Long non-coding RNA (lncRNA) MSC-AS1 triggers osteogenic differentiation by sponging microRNA (miR)-140-5p. The present study assessed the mechanism of lncRNA MSC-AS1 in OS biological features and sensitivity to cisplatin (DDP) by binding to miR-142.
MATERIAL AND METHODS: Firstly, lncRNA MSC-AS1 expression in OS tissues and cells was analyzed. OS cells were transfected with silenced MSC-AS1 to determine its role in OS biological behaviors, and we also assessed the effect of MSC-AS1 on OS sensitivity to DDP. Then, website prediction and dual-luciferase reporter gene assay were utilized for verification of the binding site between MSC-AS1 and miR-142. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were performed to determine the effect of MSC-AS1 on expression of miR-142, cyclin-dependent kinase 6 (CDK6), and the PI3K/AKT signaling pathway. Xenograft transplantation was also applied to confirm the in vitro experiments.
RESULTS: Overexpressed MSC-AS1 was associated with poor prognosis of OS patients. OS cell proliferation, invasion, and migration were reduced after silencing MSC-AS1, while cell apoptosis was enhanced. Moreover, silencing MSC-AS1 made OS cells more sensitive to DDP. Interestingly, MSC-AS1 knockdown induced miR-142 expression and reduced CDK6 levels, thereby decreasing the protein expression of p-PI3K/t-PI3K and p-AKT/t-AKT. Silencing MSC-AS1 repressed OS progression in vivo.
CONCLUSIONS: Our study demonstrated that silencing MSC-AS1 inhibited OS biological behaviors by enhancing miR-142 to decrease CDK6 and inactivating the PI3K/AKT axis. Our results may provide new insights for OS treatment.
Keywords: Cisplatin, Cyclin-Dependent Kinase 6, Osteosarcoma, Bone Neoplasms, Disease Progression, Down-Regulation, Drug Resistance, Neoplasm, Follow-Up Studies, Gene Expression Regulation, Neoplastic, Gene Knockdown Techniques, Kaplan-Meier Estimate, Osteotomy, phosphatidylinositol 3-kinase, Prognosis, Proto-Oncogene Proteins c-akt, RNA, Long Noncoding
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