The emerging role of lncRNAs in the regulation of osteosarcoma stem cells.

Objective: Osteosarcoma is a common bone sarcoma that often occurs in childhood and adolescence. In recent years, the efficacy of osteosarcoma treatments has been improved by adjuvant chemotherapies and surgical approaches. However, poor prognosis often occurs among osteosarcoma patients due to recurrence, metastasis, or drug resistance problems. Cancer stem cells (CSCs), a specific type of tumor malignant cells with stem cell-like properties, have been reported to be responsible for tumor origination, aggression, metastasis, recurrence, and drug resistance. CSCs have been identified in osteosarcomas treatment, which exhibits self-renewal, multi-potency, and enhanced drug resistance. Therefore, in the present narrative review, we intend to summarize the role of lncRNAs in regulating CSCs and their effectiveness in the treatment of osteosarcoma.

Materials And Methods: The databases PubMed (Medline), Web of Science, Embase, Scopus, and Cochrane Library, were used for the presented study. The keywords we used to complete our search are 'lncRNA', 'Stem cell', and 'osteosarcoma'. A total of over 800 relevant articles, with a time limit from 2010 to 2021, were identified according to search strategy. Duplicate records and review articles were excluded by their titles and abstracts. Finally, we found about 80 articles matching our inclusion criteria, which included about 13 relevant studies focusing on both the mechanism and effectiveness of osteosarcomas treatment among osteosarcoma patients.

Results: CD133, CD117, ALDH, and Stro-1 are validated as the stem cell biomarkers in osteosarcoma CSCs. Accumulating evidence has revealed that lncRNAs, containing HIF2PUT, SOX2-OT, MALAT1, THOR, B4GALT1-AS1, H19, PVT1, FER1L4, LINK-A, DANCR, and DLX6-AS1, play a potential role in regulating CSCs in osteosarcoma. The drug resistance, inhibition of the relapse, and metastasis in osteosarcoma could be avoided via regulating lncRNAs of targeting CSCs.

Conclusions: Multiple lncRNAs regulate CSCs in osteosarcoma via various molecular mechanisms. This review demonstrated that the method of eliminating CSCs by targeting these lncRNAs is a safe, effective, and a well-tolerated way for osteosarcoma patients, which shows a broad research prospect in tumor diagnoses and therapies. However, this method should be further demonstrated by better animal models and more clinical experiments.