10,707
Views
11
CrossRef citations to date
0
Altmetric
Review

Functions and mechanisms of circular RNAs in regulating stem cell differentiation

, , , , &
Pages 2136-2149 | Received 09 Jan 2021, Accepted 02 Apr 2021, Published online: 26 Apr 2021

References

  • Reya T, Morrison SJ, Clarke MF, et al. Stem cells, cancer, and cancer stem cells. Nature. 2001;414(6859):105–111.
  • Lancaster MA, Knoblich JA. Organogenesis in a dish: modeling development and disease using organoid technologies. Science. 2014;345(6194):1247125.
  • Castillo-Cardiel G, Lopez-Echaury AC, Saucedo-Ortiz JA, et al. Bone regeneration in mandibular fractures after the application of autologous mesenchymal stem cells, a randomized clinical trial. Dent Traumatol. 2017;33(1):38–44.
  • Mesimaki K, Lindroos B, Tornwall J, et al. Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells. Int J Oral Maxillofac Surg. 2009;38(3):201–209.
  • Clevers H, Loh KM, Nusse R. Stem cell signaling. An integral program for tissue renewal and regeneration: wnt signaling and stem cell control. Science. 2014;346(6205):1248012.
  • Ermolaeva M, Neri F, Ori A, et al. Cellular and epigenetic drivers of stem cell ageing. Nat Rev Mol Cell Biol. 2018;19(9):594–610.
  • Kristensen LS, Andersen MS, Stagsted LVW, et al. The biogenesis, biology and characterization of circular RNAs. Nat Rev Genet. 2019;20(11):675–691.
  • Sanger HL, Klotz G, Riesner D, et al. Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci U S A. 1976;73(11):3852–3856.
  • Li Z, Huang C, Bao C, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 2015;22(3):256–264. .
  • Lasda E, Parker R. Circular RNAs: diversity of form and function. RNA. 2014;20(12):1829–1842.
  • Zhang X-O, Dong R, Zhang Y, et al. Diverse alternative back-splicing and alternative splicing landscape of circular RNAs. Genome Res. 2016;26(9):1277–1287.
  • Rankin CR, Lokhandwala ZA, Huang R, et al. Linear and circular CDKN2B-AS1 expression is associated with Inflammatory Bowel Disease and participates in intestinal barrier formation. Life Sci. 2019;231:116571.
  • Zhang Y, Zhang X-O, Chen T, et al. Circular intronic long noncoding RNAs. Mol Cell. 2013;51(6):792–806.
  • Huang C, Liang D, Tatomer DC, et al. A length-dependent evolutionarily conserved pathway controls nuclear export of circular RNAs. Genes Dev. 2018;32(9–10):639–644.
  • Park OH, Ha H, Lee Y, et al. Endoribonucleolytic Cleavage of m6A-Containing RNAs by RNase P/MRP Complex. Mol Cell. 2019;74(3):494–507. e498. .
  • Kleaveland B, Shi CY, Stefano J, et al. A Network of Noncoding Regulatory RNAs Acts in the Mammalian Brain. Cell. 2018;174(2):350–362. e317. .
  • Hansen TB, Wiklund ED, Bramsen JB, et al. miRNA-dependent gene silencing involving Ago2-mediated cleavage of a circular antisense RNA. Embo J. 2011;30(21):4414–4422.
  • Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495(7441):333–338. .
  • Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495(7441):384–388.
  • Yang L, Bin Z, Hui S, et al. The Role of CDR1as in Proliferation and Differentiation of Human Umbilical Cord-Derived Mesenchymal Stem Cells. Stem Cells Int. 2019;2019:2316834.
  • Li Y, Ge Y-Z, Xu L, et al. Circular RNA ITCH: a novel tumor suppressor in multiple cancers. Life Sci. 2020;254:117176.
  • Du WW, Yang W, Chen Y, et al. Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. Eur Heart J. 2017;38(18):1402–1412.
  • Du WW, Fang L, Yang W, et al. Induction of tumor apoptosis through a circular RNA enhancing Foxo3 activity. Cell Death Differ. 2017;24(2):357–370.
  • Zeng Y, Du WW, Wu Y, et al. A Circular RNA Binds To and Activates AKT Phosphorylation and Nuclear Localization Reducing Apoptosis and Enhancing Cardiac Repair. Theranostics. 2017;7(16):3842–3855. .
  • Pamudurti NR, Bartok O, Jens M, et al. Translation of CircRNAs. Mol Cell. 2017;66(1):9–21. e27. .
  • Yang Y, Fan X, Mao M, et al. Extensive translation of circular RNAs driven by N6-methyladenosine. Cell Res. 2017;27(5):626–641. .
  • Di Timoteo G, Dattilo D, Centron-Broco A, et al. Modulation of circRNA Metabolism by m6A Modification. Cell Rep. 2020;31(6):107641. .
  • Legnini I, Di Timoteo G, Rossi F, et al. Circ-ZNF609 Is a Circular RNA that Can Be Translated and Functions in Myogenesis. Mol Cell. 2017;66(1):22–37. e29. .
  • Han B, Chao J, Yao H. Circular RNA and its mechanisms in disease: from the bench to the clinic. Pharmacol Ther. 2018;187:31–44.
  • Feng XQ, Nie SM, Huang JX, et al. Circular RNA circHIPK3 serves as a prognostic marker to promote chronic myeloid leukemia progression. Neoplasma. 2020;67(1):171–177.
  • Kun-Peng Z, Xiao-Long M, Chun-Lin Z. Overexpressed circPVT1, a potential new circular RNA biomarker, contributes to doxorubicin and cisplatin resistance of osteosarcoma cells by regulating ABCB1. Int J Biol Sci. 2018;14(3):321–330.
  • Li J, Ni S, Zhou C, et al. The expression profile and clinical application potential of hsa_circ_0000711 in colorectal cancer. Cancer Manag Res. 2018;10:2777–2784.
  • Guo Z, Zhao L, Ji S, et al. CircRNA-23525 regulates osteogenic differentiation of adipose-derived mesenchymal stem cells via miR-30a-3p. Cell Tissue Res. 2021;383(2):795–807.
  • Li H, Yang J, Wei X, et al. CircFUT10 reduces proliferation and facilitates differentiation of myoblasts by sponging miR-133a. J Cell Physiol. 2018;233(6):4643–4651. .
  • Kristensen LS, Okholm TLH, Veno MT, et al. Circular RNAs are abundantly expressed and upregulated during human epidermal stem cell differentiation. RNA Biol. 2018;15(2):280–291.
  • Lei W, Feng T, Fang X, et al. Signature of circular RNAs in human induced pluripotent stem cells and derived cardiomyocytes. Stem Cell Res Ther. 2018;9(1):56.
  • Della Bella E, Menzel U, Basoli V, et al. Differential Regulation of circRNA, miRNA, and piRNA during Early Osteogenic and Chondrogenic Differentiation of Human Mesenchymal Stromal Cells. Cells. 2020;9(2):398.
  • Chen M, Yang Y, Zeng J, et al. circRNA Expression Profile in Dental Pulp Stem Cells during Odontogenic Differentiation. Stem Cells Int. 2020;2020:1–19.
  • Chen R, Jiang T, Lei S, et al. Expression of circular RNAs during C2C12 myoblast differentiation and prediction of coding potential based on the number of open reading frames and N6-methyladenosine motifs. Cell Cycle. 2018;17(14):1832–1845.
  • Li X, Li C, Liu Z, et al. Circular RNA circ-FoxO3 Inhibits Myoblast Cells Differentiation. Cells. 2019;8(6):616.
  • Chen G, Wang Q, Li Z, et al. Circular RNA CDR1as promotes adipogenic and suppresses osteogenic differentiation of BMSCs in steroid-induced osteonecrosis of the femoral head. Bone. 2020;133:115258.
  • Siede D, Rapti K, Gorska AA, et al. Identification of circular RNAs with host gene-independent expression in human model systems for cardiac differentiation and disease. J Mol Cell Cardiol. 2017;109:48–56.
  • Qian D-Y, Yan G-B, Bai B, et al. Differential circRNA expression profiles during the BMP2-induced osteogenic differentiation of MC3T3-E1 cells. Biomed Pharmacother. 2017;90:492–499.
  • Kang Y, Guo S, Sun Q, et al. Differential circular RNA expression profiling during osteogenic differentiation in human adipose-derived stem cells. Epigenomics. 2020;12(4):289–302.
  • Li Z, Li N, Ge X, et al. Differential circular RNA expression profiling during osteogenic differentiation of stem cells from apical papilla. Epigenomics. 2019;11(9):1057–1073.
  • Zhang P, Xu H, Li R, et al. Assessment of myoblast circular RNA dynamics and its correlation with miRNA during myogenic differentiation. Int J Biochem Cell Biol. 2018;99:211–218.
  • Yang Q, Wu J, Zhao J, et al. Circular RNA expression profiles during the differentiation of mouse neural stem cells. BMC Syst Biol. 2018;12(Suppl 8):128.
  • Xie F, Zhao Y, Wang S-D, et al. Identification, characterization, and functional investigation of circular RNAs in subventricular zone of adult rat brain. J Cell Biochem. 2019;120(3):3428–3437.
  • Nicolet BP, Engels S, Aglialoro F, et al. Circular RNA expression in human hematopoietic cells is widespread and cell-type specific. Nucleic Acids Res. 2018;46(16):8168–8180.
  • Young RA. Control of the embryonic stem cell state. Cell. 2011;144(6):940–954.
  • Yu C-Y, Li T-C, Wu -Y-Y, et al. The circular RNA circBIRC6 participates in the molecular circuitry controlling human pluripotency. Nat Commun. 2017;8(1):1149.
  • Errichelli L, Dini Modigliani S, Laneve P, et al. FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons. Nat Commun. 2017;8(1):14741. .
  • You KT, Park J, Kim VN. Role of the small subunit processome in the maintenance of pluripotent stem cells. Genes Dev. 2015;29(19):2004–2009.
  • Ding D-C, Shyu W-C, Lin S-Z. Mesenchymal stem cells. Cell Transplantation. 2011;20(1):5–14.
  • Baker N, Boyette LB, Tuan RS. Characterization of bone marrow-derived mesenchymal stem cells in aging. Bone. 2015;70:37–47.
  • Chen C, Uludag H, Wang Z, et al. Noggin suppression decreases BMP-2-induced osteogenesis of human bone marrow-derived mesenchymal stem cells in vitro. J Cell Biochem. 2012;113(12):3672–3680.
  • Chia W, Liu J, Huang Y-G, et al. A circular RNA derived from DAB1 promotes cell proliferation and osteogenic differentiation of BMSCs via RBPJ/DAB1 axis. Cell Death Dis. 2020;11(5):372.
  • Ouyang Z, Tan T, Zhang X, et al. CircRNA hsa_circ_0074834 promotes the osteogenesis-angiogenesis coupling process in bone mesenchymal stem cells (BMSCs) by acting as a ceRNA for miR-942-5p. Cell Death Dis. 2019;10(12):932.
  • Wen J, Guan Z, Yu B, et al. Circular RNA hsa_circ_0076906 competes with OGN for miR-1305 biding site to alleviate the progression of osteoporosis. Int J Biochem Cell Biol. 2020;122:105719.
  • Wang X-B, Li P-B, Guo S-F, et al. circRNA_0006393 promotes osteogenesis in glucocorticoid‑induced osteoporosis by sponging miR‑145‑5p and upregulating FOXO1. Mol Med Rep. 2019;20(3):2851–2858.
  • Li X, Peng B, Zhu X, et al. Changes in related circular RNAs following ERβ knockdown and the relationship to rBMSC osteogenesis. Biochem Biophys Res Commun. 2017;493(1):100–107.
  • Li X, Chen R, Lei X, et al. Quercetin regulates ERalpha mediated differentiation of BMSCs through circular RNA. Gene. 2020;2020:145172.
  • Zhang M, Jia L, Zheng Y. circRNA Expression Profiles in Human Bone Marrow Stem Cells Undergoing Osteoblast Differentiation. Stem Cell Rev Rep. 2019;15(1):126–138.
  • Wankhade UD, Shen M, Kolhe R, et al. Advances in Adipose-Derived Stem Cells Isolation, Characterization, and Application in Regenerative Tissue Engineering. Stem Cells Int. 2016;2016:3206807.
  • Tabatabaei Qomi R, Sheykhhasan M. Adipose-derived stromal cell in regenerative medicine: a review. World J Stem Cells. 2017;9(8):107–117.
  • Shen W, Sun B, Zhou C, et al. CircFOXP1/FOXP1 promotes osteogenic differentiation in adipose-derived mesenchymal stem cells and bone regeneration in osteoporosis via miR-33a-5p. J Cell Mol Med. 2020;24(21):12513–12524.
  • Zhang D, Ni N, Wang Y, et al. CircRNA-vgll3 promotes osteogenic differentiation of adipose-derived mesenchymal stem cells via modulating miRNA-dependent integrin alpha5 expression. Cell Death Differ. 2020;28(1):283–302.
  • Huang X, Cen X, Zhang B, et al. The roles of circRFWD2 and circINO80 during NELL-1-induced osteogenesis. J Cell Mol Med. 2019;23(12):8432–8441.
  • Long T, Guo Z, Han L, et al. Differential Expression Profiles of Circular RNAs During Osteogenic Differentiation of Mouse Adipose-Derived Stromal Cells. Calcif Tissue Int. 2018;103(3):338–352.
  • Liu H, Sun Q, Wan C, et al. MicroRNA-338-3p regulates osteogenic differentiation of mouse bone marrow stromal stem cells by targeting Runx2 and Fgfr2. J Cell Physiol. 2014;229(10):1494–1502.
  • Zhu Y, Gui W, Lin X, et al. Knock-down of circular RNA H19 induces human adipose-derived stem cells adipogenic differentiation via a mechanism involving the polypyrimidine tract-binding protein 1. Exp Cell Res. 2020;387(2):111753.
  • Huang X-Q, Cen X, Sun W-T, et al. CircPOMT1 and circMCM3AP inhibit osteogenic differentiation of human adipose-derived stem cells by targeting miR-6881-3p. Am J Transl Res. 2019;11(8):4776–4788.
  • Mortada I, Mortada R, Al Bazzal M. Dental Pulp Stem Cells and Neurogenesis. Adv Exp Med Biol. 2018;1083:63–75.
  • Ge X, Li Z, Zhou Z, et al. Circular RNA SIPA1L1 promotes osteogenesis via regulating the miR-617/Smad3 axis in dental pulp stem cells. Stem Cell Res Ther. 2020;11(1):364.
  • Xie L, Guan Z, Zhang M, et al. Exosomal circLPAR1 Promoted Osteogenic Differentiation of Homotypic Dental Pulp Stem Cells by Competitively Binding to hsa-miR-31. Biomed Res Int. 2020;2020:6319395.
  • Ji F, Pan J, Shen Z, et al. The Circular RNA circRNA124534 Promotes Osteogenic Differentiation of Human Dental Pulp Stem Cells Through Modulation of the miR-496/β-Catenin Pathway. Front Cell Dev Biol. 2020;8:230.
  • Ji F, Zhu L, Pan J, et al. hsa_circ_0026827 Promotes Osteoblast Differentiation of Human Dental Pulp Stem Cells Through the Beclin1 and RUNX1 Signaling Pathways by Sponging miR-188-3p. Front Cell Dev Biol. 2020;8:470.
  • Park J-Y, Jeon SH, Choung P-H. Efficacy of periodontal stem cell transplantation in the treatment of advanced periodontitis. Cell Transplantation. 2011;20(2):271–285.
  • Gu X, Li M, Jin Y, et al. Identification and integrated analysis of differentially expressed lncRNAs and circRNAs reveal the potential ceRNA networks during PDLSC osteogenic differentiation. BMC Genet. 2017;18(1):100.
  • Li X, Zheng Y, Zheng Y, et al. Circular RNA CDR1as regulates osteoblastic differentiation of periodontal ligament stem cells via the miR-7/GDF5/SMAD and p38 MAPK signaling pathway. Stem Cell Res Ther. 2018;9(1):232.
  • Zheng J, Zhu X, He Y, et al. CircCDK8 regulates osteogenic differentiation and apoptosis of PDLSCs by inducing ER stress/autophagy during hypoxia. Ann N Y Acad Sci. 2021;1485(1):56–70.
  • Fan C-G, Zhang Q-J, Zhou J-R. Therapeutic potentials of mesenchymal stem cells derived from human umbilical cord. Stem Cell Rev Rep. 2011;7(1):195–207.
  • Ruan Z-B, Chen G-C, Zhang R, et al. 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.
  • Peng W, Zhu S, Chen J, et al. Hsa_circRNA_33287 promotes the osteogenic differentiation of maxillary sinus membrane stem cells via miR-214-3p/Runx3. Biomed Pharmacother. 2019;109:1709–1717.
  • Li Y, Bian M, Zhou Z, et al. 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.
  • Bentzinger CF, Wang YX, Rudnicki MA. Building muscle: molecular regulation of myogenesis. Cold Spring Harb Perspect Biol. 2012;4(2):a008342–a008342.
  • Giordani L, Parisi A, Le Grand F. Satellite Cell Self-Renewal. Curr Top Dev Biol. 2018;126:177–203.
  • Li L, Chen Y, Nie L, et al. MyoD-induced circular RNA CDR1as promotes myogenic differentiation of skeletal muscle satellite cells. Biochim Biophys Acta Gene Regul Mech. 2019;1862(8):807–821.
  • Shen X, Liu Z, Cao X, et al. Circular RNA profiling identified an abundant circular RNA circTMTC1 that inhibits chicken skeletal muscle satellite cell differentiation by sponging miR-128-3p. Int J Biol Sci. 2019;15(10):2265–2281.
  • Yin H, Shen X, Zhao J, et al. Circular RNA CircFAM188B Encodes a Protein That Regulates Proliferation and Differentiation of Chicken Skeletal Muscle Satellite Cells. Front Cell Dev Biol. 2020;8:522588.
  • Stockdale FE, Hager EJ, Fernyak SE, et al. Myoblasts, satellite cells, and myoblast transfer. Adv Exp Med Biol. 1990;280:7–11.
  • Du GQ, Du WJ, Liu JJ, et al. Wnt1-overexpressing skeletal myoblasts as an improved cell therapy for cardiac repair following myocardial infarction. Panminerva Med. 2015;57(4):153–166.
  • Chen B, Yu J, Guo L, et al. Circular RNA circHIPK3 Promotes the Proliferation and Differentiation of Chicken Myoblast Cells by Sponging miR-30a-3p. Cells. 2019;8(2):177.
  • Ouyang H, Chen X, Li W, et al. Circular RNA circSVIL Promotes Myoblast Proliferation and Differentiation by Sponging miR-203 in Chicken. Front Genet. 2018;9:172.
  • Chen X, Ouyang H, Wang Z, et al. A Novel Circular RNA Generated by FGFR2 Gene Promotes Myoblast Proliferation and Differentiation by Sponging miR-133a-5p and miR-29b-1-5p. Cells. 2018;7(11):199.
  • Pandey PR, Yang J-H, Tsitsipatis D, et al. circSamd4 represses myogenic transcriptional activity of PUR proteins. Nucleic Acids Res. 2020;48(7):3789–3805. .
  • Yao R, Yao Y, Li C, et al. Circ-HIPK3 plays an active role in regulating myoblast differentiation. Int J Biol Macromol. 2020;155:1432–1439.
  • Li H, Wei X, Yang J, et al. circFGFR4 Promotes Differentiation of Myoblasts via Binding miR-107 to Relieve Its Inhibition of Wnt3a. Mol Ther Nucleic Acids. 2018;11:272–283.
  • Wang X, Cao X, Dng D, et al. Circular RNA TTN Acts As a miR-432 Sponge to Facilitate Proliferation and Differentiation of Myoblasts via the IGF2/PI3K/AKT Signaling Pathway. Mol Ther Nucleic Acids. 2019;18:966–980.
  • Peng S, Song C, Li H, et al. Circular RNA SNX29 Sponges miR-744 to regulate proliferation and differentiation of myoblasts by activating the Wnt5a/Ca2+ signaling pathway. Mol Ther Nucleic Acids. 2019;16:481–493.
  • Yue B, Wang J, Ru W, et al. The circular RNA circHUWE1 sponges the miR-29b-AKT3 axis to regulate myoblast development. Mol Ther Nucleic Acids. 2020;19:1086–1097.
  • Wei X, Li H, Yang J, et al. Circular RNA profiling reveals an abundant circLMO7 that regulates myoblasts differentiation and survival by sponging miR-378a-3p. Cell Death Dis. 2017;8(10):e3153. .
  • Wang Y, Li M, Wang Y, et al. A Zfp609 circular RNA regulates myoblast differentiation by sponging miR-194-5p. Int J Biol Macromol. 2019;121:1308–1313.
  • Blanpain C, Fuchs E. Epidermal stem cells of the skin. Annu Rev Cell Dev Biol. 2006;22(1):339–373.
  • Barbollat-Boutrand L, Joly-Tonetti N, Dos Santos M, et al. MicroRNA-23b-3p regulates human keratinocyte differentiation through repression of TGIF1 and activation of the TGF-ss-SMAD2 signalling pathway. Exp Dermatol. 2017;26(1):51–57.
  • Barker N. Adult intestinal stem cells: critical drivers of epithelial homeostasis and regeneration. Nat Rev Mol Cell Biol. 2014;15(1):19–33.
  • Zhu P, Zhu X, Wu J, et al. IL-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3. Nat Immunol. 2019;20(2):183–194.
  • McKay R. Stem cells in the central nervous system. Science. 1997;276(5309):66–71.
  • Hanan M, Soreq H, Kadener S. CircRNAs in the brain. RNA Biol. 2017;14(8):1028–1034.
  • Yang M, Xiang G, Yu D, et al. Hsa_circ_0002468 regulates the neuronal differentiation of SH-SY5Y cells by modulating the MiR-561/E2F8 Axis. Med Sci Monit. 2019;25:2511–2519.
  • Salzman J, Chen RE, Olsen MN, et al. Cell-type specific features of circular RNA expression. PLoS Genet. 2013;9(9):e1003777.
  • Li X, Zhang B, Li F, et al. The mechanism and detection of alternative splicing events in circular RNAs. PeerJ. 2020;8:e10032.
  • Yan B, Zhang Y, Liang C, et al. Stem cell-derived exosomes prevent pyroptosis and repair ischemic muscle injury through a novel exosome/circHIPK3/ FOXO3a pathway. Theranostics. 2020;10(15):6728–6742.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.