The Roles of Noncoding RNAs in the Development of Osteosarcoma Stem Cells and Potential Therapeutic Targets

Overview

Journal Front Cell Dev Biol

Specialty Cell Biology

Date 2022 Mar 7

PMID 35252166

Authors

Jinxin Liu

Guanning Shang

Affiliations

Soon will be listed here.

Abstract

Osteosarcoma (OS) is the common bone tumor in children and adolescents. Because of chemotherapy resistance, the OS patients have a poor prognosis. The one reason of chemotherapeutic resistance is the development of cancer stem cells (CSCs). CSCs represent a small portion of tumor cells with the capacity of self-renewal and multipotency, which are associated with tumor initiation, metastasis, recurrence and drug resistance. Recently, noncoding RNAs (ncRNAs) have been reported to critically regulate CSCs. Therefore, in this review article, we described the role of ncRNAs, especially miRNAs, lncRNAs and circRNAs, in regulating CSCs development and potential mechanisms. Specifically, we discussed the role of multiple miRNAs in targeting CSCs, including miR-26a, miR-29b, miR-34a, miR-133a, miR-143, miR-335, miR-382, miR-499a, miR-1247, and let-7days. Moreover, we highlighted the functions of lncRNAs in regulating CSCs in OS, such as B4GALT1-AS1, DANCR, DLX6-AS1, FER1L4, HIF2PUT, LINK-A, MALAT1, SOX2-OT, and THOR. Due to the critical roles of ncRNAs in regulation of OS CSCs, targeting ncRNAs might be a novel strategy for eliminating CSCs for OS therapy.

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References

Vares G, Ahire V, Sunada S, Kim E, Sai S, Chevalier F . A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells. Radiother Oncol. 2020; 150:253-261. DOI: 10.1016/j.radonc.2020.07.034. View

Shui X, Zhou C, Lin W, Yu Y, Feng Y, Kong J . Long non-coding RNA BCAR4 promotes chondrosarcoma cell proliferation and migration through activation of mTOR signaling pathway. Exp Biol Med (Maywood). 2017; 242(10):1044-1050. PMC: 5444642. DOI: 10.1177/1535370217700735. View

Li J, Wang L, Liu Z, Zu C, Xing F, Yang P . MicroRNA-494 inhibits cell proliferation and invasion of chondrosarcoma cells in vivo and in vitro by directly targeting SOX9. Oncotarget. 2015; 6(28):26216-29. PMC: 4694896. DOI: 10.18632/oncotarget.4460. View

Sun X, Dai G, Yu L, Hu Q, Chen J, Guo W . miR-143-3p inhibits the proliferation, migration and invasion in osteosarcoma by targeting FOSL2. Sci Rep. 2018; 8(1):606. PMC: 5766605. DOI: 10.1038/s41598-017-18739-3. View

Li M, Ma W . miR-26a Reverses Multidrug Resistance in Osteosarcoma by Targeting MCL1. Front Cell Dev Biol. 2021; 9:645381. PMC: 8012539. DOI: 10.3389/fcell.2021.645381. View

Di Fiore R, Drago-Ferrante R, Pentimalli F, Di Marzo D, Forte I, DAnneo A . MicroRNA-29b-1 impairs in vitro cell proliferation, self‑renewal and chemoresistance of human osteosarcoma 3AB-OS cancer stem cells. Int J Oncol. 2014; 45(5):2013-23. PMC: 4432724. DOI: 10.3892/ijo.2014.2618. View

Liang X, Xu C, Wang W, Li X . The DNMT1/miR-34a Axis Is Involved in the Stemness of Human Osteosarcoma Cells and Derived Stem-Like Cells. Stem Cells Int. 2019; 2019:7028901. PMC: 6875320. DOI: 10.1155/2019/7028901. View

Li Z, Li X, Xu D, Chen X, Li S, Zhang L . An update on the roles of circular RNAs in osteosarcoma. Cell Prolif. 2020; 54(1):e12936. PMC: 7791175. DOI: 10.1111/cpr.12936. View

Ghafouri-Fard S, Shirvani-Farsani Z, Hussen B, Taheri M . The critical roles of lncRNAs in the development of osteosarcoma. Biomed Pharmacother. 2021; 135:111217. DOI: 10.1016/j.biopha.2021.111217. View

10.

Liu Z, Liang Z, Li L, Zhou Y, Wang Z, Gu W . MiR-335 functions as a tumor suppressor and regulates survivin expression in osteosarcoma. Eur Rev Med Pharmacol Sci. 2016; 20(7):1251-7. View

11.

Li Y, Liu J, Zhou J, Chen R, Cen C . LncRNA HULC induces the progression of osteosarcoma by regulating the miR-372-3p/HMGB1 signalling axis. Mol Med. 2020; 26(1):26. PMC: 7081592. DOI: 10.1186/s10020-020-00155-5. View

12.

Huang Y, Zhang Y, Li X, Liu H, Yang Q, Jia L . The long non-coding RNA landscape of periodontal ligament stem cells subjected to compressive force. Eur J Orthod. 2018; 41(4):333-342. DOI: 10.1093/ejo/cjy057. View

13.

Humphries B, Wang Z, Yang C . MicroRNA Regulation of Breast Cancer Stemness. Int J Mol Sci. 2021; 22(7). PMC: 8038508. DOI: 10.3390/ijms22073756. View

14.

Fujiwara T, Katsuda T, Hagiwara K, Kosaka N, Yoshioka Y, Takahashi R . Clinical relevance and therapeutic significance of microRNA-133a expression profiles and functions in malignant osteosarcoma-initiating cells. Stem Cells. 2014; 32(4):959-73. DOI: 10.1002/stem.1618. View

15.

Wang Y, Zhang Y, Yang T, Zhao W, Wang N, Li P . Long non-coding RNA MALAT1 for promoting metastasis and proliferation by acting as a ceRNA of miR-144-3p in osteosarcoma cells. Oncotarget. 2017; 8(35):59417-59434. PMC: 5601743. DOI: 10.18632/oncotarget.19727. View

16.

Zhao D, Wang S, Chu X, Han D . LncRNA HIF2PUT inhibited osteosarcoma stem cells proliferation, migration and invasion by regulating HIF2 expression. Artif Cells Nanomed Biotechnol. 2019; 47(1):1342-1348. DOI: 10.1080/21691401.2019.1596934. View

17.

Yang G, Wu Y, Wan R, Sang H, Liu H, Huang W . The role of non‑coding RNAs in the regulation, diagnosis, prognosis and treatment of osteosarcoma (Review). Int J Oncol. 2021; 59(3). DOI: 10.3892/ijo.2021.5249. View

18.

Song Q, Shi Z, Zhang Y, Ji L, Wang K, Duan D . Downregulation of microRNA-26a is associated with metastatic potential and the poor prognosis of osteosarcoma patients. Oncol Rep. 2014; 31(3):1263-70. DOI: 10.3892/or.2014.2989. View

19.

Lu J, Song G, Tang Q, Yin J, Zou C, Zhao Z . MiR-26a inhibits stem cell-like phenotype and tumor growth of osteosarcoma by targeting Jagged1. Oncogene. 2016; 36(2):231-241. DOI: 10.1038/onc.2016.194. View

20.

Wei Q, Yao J, Yang Y . MicroRNA-1247 inhibits the viability and metastasis of osteosarcoma cells via targeting NRP1 and mediating Wnt/β-catenin pathway. Eur Rev Med Pharmacol Sci. 2019; 23(17):7266-7274. DOI: 10.26355/eurrev_201909_18831. View