Circular RNAs in Stem Cells: from Basic Research to Clinical Implications

Overview

Journal Biosci Rep

Specialty Cell Biology

Date 2021 Dec 15

PMID 34908111

Citations 8

Authors

Hui-Juan Lu

Juan Li

Guodong Yang

Cun-Jian Yi

Daping Zhang

Fenggang Yu

Zhaowu Ma

Affiliations

Soon will be listed here.

Abstract

Circular RNAs (circRNAs) are a special class of endogenous RNAs with a wide variety of pathophysiological functions via diverse mechanisms, including transcription, microRNA (miRNA) sponge, protein sponge/decoy, and translation. Stem cells are pluripotent cells with unique properties of self-renewal and differentiation. Dysregulated circRNAs identified in various stem cell types can affect stem cell self-renewal and differentiation potential by manipulating stemness. However, the emerging roles of circRNAs in stem cells remain largely unknown. This review summarizes the major functions and mechanisms of action of circRNAs in stem cell biology and disease progression. We also highlight circRNA-mediated common pathways in diverse stem cell types and discuss their diagnostic significance with respect to stem cell-based therapy.

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References

Olschewski D, Rueger M . The silencing of circular RNA in neural stem cells - A gateway to new therapeutic strategies in cerebral ischemia?. EBioMedicine. 2020; 53:102705. PMC: 7063169. DOI: 10.1016/j.ebiom.2020.102705. View

Li F, Yang Q, He A, Yang B . Circular RNAs in cancer: Limitations in functional studies and diagnostic potential. Semin Cancer Biol. 2020; 75:49-61. DOI: 10.1016/j.semcancer.2020.10.002. View

Li Y, Sarkar F . MicroRNA Targeted Therapeutic Approach for Pancreatic Cancer. Int J Biol Sci. 2016; 12(3):326-37. PMC: 4753161. DOI: 10.7150/ijbs.15017. View

Feng Z, Meng S, Zhou H, Xu Z, Tang Y, Li P . Functions and Potential Applications of Circular RNAs in Cancer Stem Cells. Front Oncol. 2019; 9:500. PMC: 6584801. DOI: 10.3389/fonc.2019.00500. View

Jian X, He H, Zhu J, Zhang Q, Zheng Z, Liang X . Hsa_circ_001680 affects the proliferation and migration of CRC and mediates its chemoresistance by regulating BMI1 through miR-340. Mol Cancer. 2020; 19(1):20. PMC: 6993513. DOI: 10.1186/s12943-020-1134-8. View

Lei W, Feng T, Fang X, Yu Y, Yang J, Zhao Z . Signature of circular RNAs in human induced pluripotent stem cells and derived cardiomyocytes. Stem Cell Res Ther. 2018; 9(1):56. PMC: 5845222. DOI: 10.1186/s13287-018-0793-5. View

Li Y, Bian M, Zhou Z, Wu X, Ge X, Xiao T . Circular RNA SIPA1L1 regulates osteoblastic differentiation of stem cells from apical papilla via miR-204-5p/ALPL pathway. Stem Cell Res Ther. 2020; 11(1):461. PMC: 7607702. DOI: 10.1186/s13287-020-01970-7. View

Grimaldi A, Zarone M, Irace C, Zappavigna S, Lombardi A, Kawasaki H . Non-coding RNAs as a new dawn in tumor diagnosis. Semin Cell Dev Biol. 2017; 78:37-50. DOI: 10.1016/j.semcdb.2017.07.035. View

Li L, Chen Y, Nie L, Ding X, Zhang X, Zhao W . MyoD-induced circular RNA CDR1as promotes myogenic differentiation of skeletal muscle satellite cells. Biochim Biophys Acta Gene Regul Mech. 2019; 1862(8):807-821. DOI: 10.1016/j.bbagrm.2019.07.001. View

10.

Clara J, Monge C, Yang Y, Takebe N . Targeting signalling pathways and the immune microenvironment of cancer stem cells - a clinical update. Nat Rev Clin Oncol. 2019; 17(4):204-232. DOI: 10.1038/s41571-019-0293-2. View

11.

Xu T, Wang M, Jiang L, Ma L, Wan L, Chen Q . CircRNAs in anticancer drug resistance: recent advances and future potential. Mol Cancer. 2020; 19(1):127. PMC: 7429705. DOI: 10.1186/s12943-020-01240-3. View

12.

Sharma A, Sances S, Workman M, Svendsen C . Multi-lineage Human iPSC-Derived Platforms for Disease Modeling and Drug Discovery. Cell Stem Cell. 2020; 26(3):309-329. PMC: 7159985. DOI: 10.1016/j.stem.2020.02.011. View

13.

Li J, Zhang G, Liu C, Xiang X, Le M, Sethi G . The potential role of exosomal circRNAs in the tumor microenvironment: insights into cancer diagnosis and therapy. Theranostics. 2022; 12(1):87-104. PMC: 8690929. DOI: 10.7150/thno.64096. View

14.

Ruan Z, Chen G, Zhang R, Zhu L . Circular RNA expression profiles during the differentiation of human umbilical cord-derived mesenchymal stem cells into cardiomyocyte-like cells. J Cell Physiol. 2019; 234(9):16412-16423. DOI: 10.1002/jcp.28310. View

15.

Khan A, Ahmed E, Elareer N, Junejo K, Steinhoff M, Uddin S . Role of miRNA-Regulated Cancer Stem Cells in the Pathogenesis of Human Malignancies. Cells. 2019; 8(8). PMC: 6721829. DOI: 10.3390/cells8080840. View

16.

Ashwal-Fluss R, Meyer M, Pamudurti N, Ivanov A, Bartok O, Hanan M . circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014; 56(1):55-66. DOI: 10.1016/j.molcel.2014.08.019. View

17.

Li Z, Huang C, Bao C, Chen L, Lin M, Wang X . Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 2015; 22(3):256-64. DOI: 10.1038/nsmb.2959. View

18.

Wang F, Chen X, Han Y, Xi S, Wu G . circRNA CDR1as Regulated the Proliferation of Human Periodontal Ligament Stem Cells under a Lipopolysaccharide-Induced Inflammatory Condition. Mediators Inflamm. 2019; 2019:1625381. PMC: 6754938. DOI: 10.1155/2019/1625381. View

19.

Kristensen L, Okholm T, Veno M, Kjems J . Circular RNAs are abundantly expressed and upregulated during human epidermal stem cell differentiation. RNA Biol. 2017; 15(2):280-291. PMC: 5798954. DOI: 10.1080/15476286.2017.1409931. View

20.

Sneha S, Nagare R, Sidhanth C, Krishnapriya S, Garg M, Ramachandran B . The hedgehog pathway regulates cancer stem cells in serous adenocarcinoma of the ovary. Cell Oncol (Dordr). 2020; 43(4):601-616. DOI: 10.1007/s13402-020-00504-w. View