Effect of lncRNA XLOC_005950 knockout by CRISPR/Cas9 gene editing on energy metabolism and proliferation in osteosarcoma MG63 cells mediated by hsa‑miR‑542‑3p

• Published in: Oncology letters Vol. 22; no. 3; p. 1
• Main Authors: Jia, Zhen, Wang, Yadong, Sun, Xiaoya, Zhao, Xuefeng, Zhang, Yan, Xu, Shuangyan, Wang, Yisheng, Li, Yuebai
• Format: Journal Article
• Language: English
• Published: Athens Spandidos Publications 01.09.2021; Spandidos Publications UK Ltd; D.A. Spandidos
• Subjects: Analysis; Apoptosis; Binding sites; Biotechnology; Bone cancer; Bone surgery; Cell growth; CRISPR; Dextrose; Gastric cancer; Gene expression; Genes; Genetic research; Genetic transcription; Genome editing; Genomes; Glucose; Health savings accounts; Kinases; Metabolism; MicroRNA; MicroRNAs; Oncology; Operating systems; Osteosarcoma; Sarcoma; Scientific equipment and supplies industry; United States; Beijing China; China
• ISSN: 1792-1074; 1792-1082
• DOI: 10.3892/ol.2021.12930

Cancer cells use glucose via glycolysis to maintain tumor cell proliferation. However, the effect of long non-coding RNAs (lncRNAs) on glycolysis in osteosarcoma (OS) cells remains unclear. The present study aimed to investigate the involvement of the lncRNA XLOC_005950/hsa-microRNA (miR)-542-3p/phosphofructokinase, muscle (PFKM) axis in the regulation of glucose metabolism, cell proliferation and apoptosis in the progression of OS. lncRNA XLOC_005950, hsa-miR-542-3p and PFKM expression in OS tissues and cells was detected via reverse transcription-quantitative PCR analysis. CRISPR/Cas9 gene editing was used to knockout lncRNA XLOC_005950 expression in MG63 cells. Cell Counting Kit-8 assay, flow cytometry, PFKM activity, and glucose and lactic acid content determination were performed to assess the effects of lncRNA XLOC_005950 knockout and overexpression of hsa-miR-542-3p on the phenotypes of OS cells. The dual-luciferase reporter assay was performed to confirm the targeting associations between lncRNA XLOC_005950, hsa-miR-542-3p and PFKM. The results demonstrated that lncRNA XLOC_005950 expression was upregulated in OS tissues and cells. Functional experiments indicated that lncRNA XLOC_005950 knockout decreased PFKM activity, the intracellular glucose and lactic acid content, and cell proliferation, while increasing apoptosis of OS cells. Furthermore, lncRNA XLOC_005950 knockout upregulated hsa-miR-542-3p expression and downregulated PFKM expression. Overexpression of hsa-miR-542-3p suppressed PFKM expression. Furthermore, lncRNA XLOC_005950, as the molecular sponge of miR-542-3p in OS, modulated the downstream target gene, PFKM. Taken together, the results of the present study suggest that lncRNA XLOC_005950 knockout may inhibit the progression of OS via hsa-miR-542-3p-mediated regulation of PFKM expression. Key words: long non-coding RNA, osteosarcoma, aerobic glycolysis, CRISPR/Cas9, hsa-microRNA-542-3p, proliferation