Circular RNAs (circRNAs) constitute a recently recognized group of noncoding transcripts that function as posttranscriptional regulators of gene expression at a new level. Recent developments in experimental methods together with rapidly evolving bioinformatics approaches have accelerated the exploration of circRNAs. The differentiation of hematopoietic stem cells into a broad spectrum of specialized blood lineages is a tightly regulated process that depends on a multitude of factors, including circRNAs. However, despite the growing number of circRNAs described to date, the roles of the majority of them in hematopoiesis remain unknown. Given their stability and disease-specific expression, circRNAs have been acknowledged as novel promising biomarkers and therapeutic targets. In this paper, the biogenesis, characteristics, and roles of circRNAs are reviewed with an emphasis on their currently recognized or presumed involvement in hematopoiesis, especially in acute myeloid leukemia and myelodysplastic syndrome.

Institute of Hematology and Blood Transfusion 128 20 Prague Czech Republic

See more in PubMed

ENCODE Project Consortium An Integrated Encyclopedia of DNA Elements in the Human Genome. Nature. 2012;489:57–74. doi: 10.1038/nature11247. PubMed DOI PMC

Sanger H.L., Klotz G., Riesner D., Gross H.J., Kleinschmidt A.K. Viroids are Single-Stranded Covalently Closed Circular RNA Molecules Existing as Highly Base-Paired Rod-Like Structures. Proc. Natl. Acad. Sci. USA. 1976;73:3852–3856. doi: 10.1073/pnas.73.11.3852. PubMed DOI PMC

Cocquerelle C., Mascrez B., Hétuin D., Bailleul B. Mis-Splicing Yields Circular RNA Molecules. FASEB J. 1993;7:155–160. doi: 10.1096/fasebj.7.1.7678559. PubMed DOI

Bailleul B. During in Vivo Maturation of Eukaryotic Nuclear mRNA, Splicing Yields Excised Exon Circles. Nucleic Acids Res. 1996;24:1015–1019. doi: 10.1093/nar/24.6.1015. PubMed DOI PMC

Pasman Z., Been M.D., Garcia-Blanco M.A. Exon Circularization in Mammalian Nuclear Extracts. RNA. 1996;2:603–610. PubMed PMC

Nigro J.M., Cho K.R., Fearon E.R., Kern S.E., Ruppert J.M., Oliner J.D., Kinzler K.W., Vogelstein B. Scrambled. Exons. Cell. 1991;64:607–613. doi: 10.1016/0092-8674(91)90244-S. PubMed DOI

Capel B., Swain A., Nicolis S., Hacker A., Walter M., Koopman P., Goodfellow P., Lovell-Badge R. Circular Transcripts of the Testis-Determining Gene Sry in Adult Mouse Testis. Cell. 1993;73:1019–1030. doi: 10.1016/0092-8674(93)90279-Y. PubMed DOI

Hansen T.B., Jensen T.I., Clausen B.H., Bramsen J.B., Finsen B., Damgaard C.K., Kjems J. Natural RNA Circles Function as Efficient microRNA Sponges. Nature. 2013;495:384–388. doi: 10.1038/nature11993. PubMed DOI

Glažar P., Papavasileiou P., Rajewsky N. circBase: A Database for Circular RNAs. RNA. 2014;20:1666–1670. doi: 10.1261/rna.043687.113. PubMed DOI PMC

Salzman J., Chen R.E., Olsen M.N., Wang P.L., Brown P.O. Cell-Type Specific Features of Circular RNA Expression. PLoS Genet. 2013;9:e1003777. doi: 10.1371/annotation/f782282b-eefa-4c8d-985c-b1484e845855. PubMed DOI PMC

Rybak-Wolf A., Stottmeister C., Glažar P., Jens M., Pino N., Giusti S., Hanan M., Behm M., Bartok O., Ashwal-Fluss R., et al. Circular RNAs in the Mammalian Brain are Highly Abundant, Conserved, and Dynamically Expressed. Mol. Cell. 2015;58:870–885. doi: 10.1016/j.molcel.2015.03.027. PubMed DOI

Jeck W.R., Sorrentino J.A., Wang K., Slevin M.K., Burd C.E., Liu J., Marzluff W.F., Sharpless N.E. Circular RNAs are Abundant, Conserved, and Associated with ALU Repeats. RNA. 2013;19:426. doi: 10.1261/rna.035667.112. PubMed DOI PMC

Salzman J., Gawad C., Wang P.L., Lacayo N., Brown P.O. Circular RNAs are the Predominant Transcript Isoform from Hundreds of Human Genes in Diverse Cell Types. PLoS ONE. 2012;7:e30733. doi: 10.1371/journal.pone.0030733. PubMed DOI PMC

Enuka Y., Lauriola M., Feldman M.E., Sas-Chen A., Ulitsky I., Yarden Y. Circular RNAs are Long-Lived and Display Only Minimal Early Alterations in Response to a Growth Factor. Nucleic Acids Res. 2016;44:1370–1383. doi: 10.1093/nar/gkv1367. PubMed DOI PMC

Chen L. The Biogenesis and Emerging Roles of Circular RNAs. Nat. Rev. Mol. Cell Biol. 2016;17:205–211. doi: 10.1038/nrm.2015.32. PubMed DOI

Ashwal-Fluss R., Meyer M., Pamudurti N.R., Ivanov A., Bartok O., Hanan M., Evantal N., Memczak S., Rajewsky N., Kadener S. circRNA Biogenesis Competes with Pre-mRNA Splicing. Mol. Cell. 2014;56:55–66. doi: 10.1016/j.molcel.2014.08.019. PubMed DOI

Starke S., Jost I., Rossbach O., Schneider T., Schreiner S., Hung L., Bindereif A. Exon Circularization Requires Canonical Splice Signals. Cell Rep. 2015;10:103–111. doi: 10.1016/j.celrep.2014.12.002. PubMed DOI

Zhang X., Wang H., Zhang Y., Lu X., Chen L., Yang L. Complementary Sequence-Mediated Exon Circularization. Cell. 2014;159:134–147. doi: 10.1016/j.cell.2014.09.001. PubMed DOI

Li Z., Huang C., Bao C., Chen L., Lin M., Wang X., Zhong G., Yu B., Hu W., Dai L., et al. Exon-Intron Circular RNAs Regulate Transcription in the Nucleus. Nat. Struct. Mol. Biol. 2015;22:256–264. doi: 10.1038/nsmb.2959. PubMed DOI

Zhang Y., Zhang X., Chen T., Xiang J., Yin Q., Xing Y., Zhu S., Yang L., Chen L. Circular Intronic Long Noncoding RNAs. Mol. Cell. 2013;51:792–806. doi: 10.1016/j.molcel.2013.08.017. PubMed DOI

Memczak S., Jens M., Elefsinioti A., Torti F., Krueger J., Rybak A., Maier L., Mackowiak S.D., Gregersen L.H., Munschauer M., et al. Circular RNAs are a Large Class of Animal RNAs with Regulatory Potency. Nature. 2013;495:333–338. doi: 10.1038/nature11928. PubMed DOI

Guarnerio J., Bezzi M., Jeong J.C., Paffenholz S.V., Berry K., Naldini M.M., Lo-Coco F., Tay Y., Beck A.H., Pandolfi P.P. Oncogenic Role of Fusion-circRNAs Derived from Cancer-Associated Chromosomal Translocations. Cell. 2016;165:289–302. doi: 10.1016/j.cell.2016.03.020. PubMed DOI

Floris G., Zhang L., Follesa P., Sun T. Regulatory Role of Circular RNAs and Neurological Disorders. Mol. Neurobiol. 2017;54:5156–5165. doi: 10.1007/s12035-016-0055-4. PubMed DOI PMC

Wang Y., Lu T., Wang Q., Liu J., Jiao W. Circular RNAs: Crucial Regulators in the Human Body (Review) Oncol. Rep. 2018;40:3119–3135. doi: 10.3892/or.2018.6733. PubMed DOI PMC

Liang D., Wilusz J.E. Short Intronic Repeat Sequences Facilitate Circular RNA Production. Genes Dev. 2014;28:2233–2247. doi: 10.1101/gad.251926.114. PubMed DOI PMC

Wilusz J.E. Repetitive Elements Regulate Circular RNA Biogenesis. Mobile Genetic Elements. 2015;5:39–45. doi: 10.1080/2159256X.2015.1045682. PubMed DOI PMC

Ivanov A., Memczak S., Wyler E., Torti F., Porath H.T., Orejuela M.R., Piechotta M., Levanon E.Y., Landthaler M., Dieterich C., et al. Analysis of Intron Sequences Reveals Hallmarks of Circular RNA Biogenesis in Animals. Cell Rep. 2015;10:170–177. doi: 10.1016/j.celrep.2014.12.019. PubMed DOI

Aktaş T., Avşar Ilık İ., Maticzka D., Bhardwaj V., Pessoa Rodrigues C., Mittler G., Manke T., Backofen R., Akhtar A. DHX9 Suppresses RNA Processing Defects Originating from the Alu Invasion of the Human Genome. Nature. 2017;544:115–119. doi: 10.1038/nature21715. PubMed DOI

Yu C., Li T., Wu Y., Yeh C., Chiang W., Chuang C., Kuo H. The Circular RNA circBIRC6 Participates in the Molecular Circuitry Controlling Human Pluripotency. Nat. Commun. 2017;8:1149. doi: 10.1038/s41467-017-01216-w. PubMed DOI PMC

Kramer M.C., Liang D., Tatomer D.C., Gold B., March Z.M., Cherry S., Wilusz J.E. Combinatorial Control of Drosophila Circular RNA Expression by Intronic Repeats, hnRNPs, and SR Proteins. Genes Dev. 2015;29:2168–2182. doi: 10.1101/gad.270421.115. PubMed DOI PMC

Du W.W., Yang W., Liu E., Yang Z., Dhaliwal P., Yang B.B. Foxo3 Circular RNA Retards Cell Cycle Progression Via Forming Ternary Complexes with p21 and CDK2. Nucleic Acids Res. 2016;44:2846–2858. doi: 10.1093/nar/gkw027. PubMed DOI PMC

Hansen T.B., Wiklund E.D., Bramsen J.B., Villadsen S.B., Statham A.L., Clark S.J., Kjems J. miRNA-Dependent Gene Silencing Involving Ago2-Mediated Cleavage of a Circular Antisense RNA. EMBO J. 2011;30:4414–4422. doi: 10.1038/emboj.2011.359. PubMed DOI PMC

Du W.W., Zhang C., Yang W., Yong T., Awan F.M., Yang B.B. Identifying and Characterizing circRNA-Protein Interaction. Theranostics. 2017;7:4183–4191. doi: 10.7150/thno.21299. PubMed DOI PMC

Legnini I., Di Timoteo G., Rossi F., Morlando M., Briganti F., Sthandier O., Fatica A., Santini T., Andronache A., Wade M., et al. Circ-ZNF609 is a Circular RNA that can be Translated and Functions in Myogenesis. Mol. Cell. 2017;66:22–37.e9. doi: 10.1016/j.molcel.2017.02.017. PubMed DOI PMC

Pamudurti N.R., Bartok O., Jens M., Ashwal-Fluss R., Stottmeister C., Ruhe L., Hanan M., Wyler E., Perez-Hernandez D., Ramberger E., et al. Translation of CircRNAs. Mol. Cell. 2017;66:9–21.e7. doi: 10.1016/j.molcel.2017.02.021. PubMed DOI PMC

Hansen T.B., Kjems J., Damgaard C.K. Circular RNA and miR-7 in Cancer. Cancer Res. 2013;73:5609–5612. doi: 10.1158/0008-5472.CAN-13-1568. PubMed DOI

Militello G., Weirick T., John D., Döring C., Dimmeler S., Uchida S. Screening and Validation of lncRNAs and circRNAs as miRNA Sponges. Brief. Bioinform. 2017;18:780–788. doi: 10.1093/bib/bbw053. PubMed DOI

Dudekula D.B., Panda A.C., Grammatikakis I., De S., Abdelmohsen K., Gorospe M. CircInteractome: A Web Tool for Exploring Circular RNAs and their Interacting Proteins and microRNAs. RNA Biol. 2016;13:34–42. doi: 10.1080/15476286.2015.1128065. PubMed DOI PMC

Dong R., Ma X., Li G., Yang L. CIRCpedia V2: An Updated Database for Comprehensive Circular RNA Annotation and Expression Comparison. Genom. Proteomics Bioinform. 2018;16:226–233. doi: 10.1016/j.gpb.2018.08.001. PubMed DOI PMC

Wu S., Liu H., Huang P., Chang I.Y., Lee C., Yang C., Tsai W., Tan B.C. circlncRNAnet: An Integrated Web-Based Resource for Mapping Functional Networks of Long Or Circular Forms of Noncoding RNAs. Gigascience. 2018;7:1–10. doi: 10.1093/gigascience/gix118. PubMed DOI PMC

Fan C., Lei X., Fang Z., Jiang Q., Wu F. CircR2Disease: A Manually Curated Database for Experimentally Supported Circular RNAs Associated with various Diseases. Database (Oxford) 2018;2018 doi: 10.1093/database/bay044. PubMed DOI PMC

Xia S., Feng J., Lei L., Hu J., Xia L., Wang J., Xiang Y., Liu L., Zhong S., Han L., et al. Comprehensive Characterization of Tissue-Specific Circular RNAs in the Human and Mouse Genomes. Brief. Bioinform. 2017;18:984–992. doi: 10.1093/bib/bbw081. PubMed DOI

Xia S., Feng J., Chen K., Ma Y., Gong J., Cai F., Jin Y., Gao Y., Xia L., Chang H., et al. CSCD: A Database for Cancer-Specific Circular RNAs. Nucleic Acids Res. 2018;46:D925–D929. doi: 10.1093/nar/gkx863. PubMed DOI PMC

Szabo L., Salzman J. Detecting Circular RNAs: Bioinformatic and Experimental Challenges. Nature reviews. Genetics. 2016;17:679–692. PubMed PMC

Vincent H.A., Deutscher M.P. Substrate Recognition and Catalysis by the Exoribonuclease RNase. R.J. Biol. Chem. 2006;281:29769–29775. doi: 10.1074/jbc.M606744200. PubMed DOI

Jeck W.R., Sharpless N.E. Detecting and Characterizing Circular RNAs. Nat. Biotechnol. 2014;32:453–461. doi: 10.1038/nbt.2890. PubMed DOI PMC

Pandey P.R., Rout P.K., Das A., Gorospe M., Panda A.C. RPAD (RNase R Treatment, Polyadenylation, and Poly(A)+ RNA Depletion) Method to Isolate Highly Pure Circular RNA. Methods. 2019;155:41–48. doi: 10.1016/j.ymeth.2018.10.022. PubMed DOI PMC

Barrett S.P., Salzman J. Circular RNAs: Analysis, Expression and Potential Functions. Development. 2016;143:1838–1847. doi: 10.1242/dev.128074. PubMed DOI PMC

Zaghlool A., Ameur A., Wu C., Westholm J.O., Niazi A., Manivannan M., Bramlett K., Nilsson M., Feuk L. Expression Profiling and in Situ Screening of Circular RNAs in Human Tissues. Sci. Rep. 2018;8:1–12. doi: 10.1038/s41598-018-35001-6. PubMed DOI PMC

Szabo L., Morey R., Palpant N.J., Wang P.L., Afari N., Jiang C., Parast M.M., Murry C.E., Laurent L.C., Salzman J. Statistically Based Splicing Detection Reveals Neural Enrichment and Tissue-Specific Induction of Circular RNA during Human Fetal Development. Genome Biol. 2015;16:126. doi: 10.1186/s13059-015-0690-5. PubMed DOI PMC

Chuang T., Wu C., Chen C., Hung L., Chiang T., Yang M. NCLscan: Accurate Identification of Non-Co-Linear Transcripts (Fusion, Trans-Splicing and Circular RNA) with a Good Balance between Sensitivity and Precision. Nucleic Acids Res. 2016;44:e29. doi: 10.1093/nar/gkv1013. PubMed DOI PMC

Meng X., Li X., Zhang P., Wang J., Zhou Y., Chen M. Circular RNA: An Emerging Key Player in RNA World. Brief. Bioinform. 2017;18:547–557. doi: 10.1093/bib/bbw045. PubMed DOI

Zhang Z., Qi S., Tang N., Zhang X., Chen S., Zhu P., Ma L., Cheng J., Xu Y., Lu M., et al. Discovery of Replicating Circular RNAs by RNA-Seq and Computational Algorithms. PLoS Pathog. 2014;10:e1004553. doi: 10.1371/journal.ppat.1004553. PubMed DOI PMC

Wang K., Singh D., Zeng Z., Coleman S.J., Huang Y., Savich G.L., He X., Mieczkowski P., Grimm S.A., Perou C.M., et al. MapSplice: Accurate Mapping of RNA-Seq Reads for Splice Junction Discovery. Nucleic Acids Res. 2010;38:e178. doi: 10.1093/nar/gkq622. PubMed DOI PMC

Cheng J., Metge F., Dieterich C. Specific Identification and Quantification of Circular RNAs from Sequencing Data. Bioinformatics. 2016;32:1094–1096. doi: 10.1093/bioinformatics/btv656. PubMed DOI

Jakobi T., Uvarovskii A., Dieterich C. Circtools—A One-Stop Software Solution for Circular RNA Research. Bioinformatics. 2019;35:2326–2328. doi: 10.1093/bioinformatics/bty948. PubMed DOI PMC

Gao Y., Wang J., Zhao F. CIRI: An Efficient and Unbiased Algorithm for De Novo Circular RNA Identification. Genome Biol. 2015;16:4. doi: 10.1186/s13059-014-0571-3. PubMed DOI PMC

Li X., Chu C., Pei J., Măndoiu I., Wu Y. CircMarker: A Fast and Accurate Algorithm for Circular RNA Detection. BMC Genomics. 2018;19:572. doi: 10.1186/s12864-018-4926-0. PubMed DOI PMC

Zeng X., Lin W., Guo M., Zou Q. A Comprehensive Overview and Evaluation of Circular RNA Detection Tools. PLoS Comput. Biol. 2017;13:e1005420. doi: 10.1371/journal.pcbi.1005420. PubMed DOI PMC

Hansen T.B., Venø M.T., Damgaard C.K., Kjems J. Comparison of Circular RNA Prediction Tools. Nucleic Acids Res. 2016;44:e58. doi: 10.1093/nar/gkv1458. PubMed DOI PMC

Li S., Teng S., Xu J., Su G., Zhang Y., Zhao J., Zhang S., Wang H., Qin W., Lu Z.J., et al. Microarray is an Efficient Tool for circRNA Profiling. Brief. Bioinform. 2019;20:1420–1433. doi: 10.1093/bib/bby006. PubMed DOI

Zheng Q., Bao C., Guo W., Li S., Chen J., Chen B., Luo Y., Lyu D., Li Y., Shi G., et al. Circular RNA Profiling Reveals an Abundant circHIPK3 that Regulates Cell Growth by Sponging Multiple miRNAs. Nat. Commun. 2016;7:11215. doi: 10.1038/ncomms11215. PubMed DOI PMC

Li X., Yang L., Chen L. The Biogenesis, Functions, and Challenges of Circular RNAs. Mol. Cell. 2018;71:428–442. doi: 10.1016/j.molcel.2018.06.034. PubMed DOI

Panda A.C., Gorospe M. Detection and Analysis of Circular RNAs by RT-PCR. Bio. Protoc. 2018;8:e2775. doi: 10.21769/BioProtoc.2775. PubMed DOI PMC

Panda A.C., Grammatikakis I., Kim K.M., De S., Martindale J.L., Munk R., Yang X., Abdelmohsen K., Gorospe M. Identification of Senescence-Associated Circular RNAs (SAC-RNAs) Reveals Senescence Suppressor CircPVT1. Nucleic Acids Res. 2017;45:4021–4035. doi: 10.1093/nar/gkw1201. PubMed DOI PMC

Hindson B.J., Ness K.D., Masquelier D.A., Belgrader P., Heredia N.J., Makarewicz A.J., Bright I.J., Lucero M.Y., Hiddessen A.L., Legler T.C., et al. High-Throughput Droplet Digital PCR System for Absolute Quantitation of DNA Copy Number. Anal. Chem. 2011;83:8604–8610. doi: 10.1021/ac202028g. PubMed DOI PMC

Li T., Shao Y., Fu L., Xie Y., Zhu L., Sun W., Yu R., Xiao B., Guo J. Plasma Circular RNA Profiling of Patients with Gastric Cancer and their Droplet Digital RT-PCR Detection. J. Mol. Med. 2018;96:85–96. doi: 10.1007/s00109-017-1600-y. PubMed DOI

Czubak K., Taylor K., Piasecka A., Sobczak K., Kozlowska K., Philips A., Sedehizadeh S., Brook J.D., Wojciechowska M., Kozlowski P. Global Increase in Circular RNA Levels in Myotonic Dystrophy. Front Genet. 2019;10:649. doi: 10.3389/fgene.2019.00649. PubMed DOI PMC

Pandey P.R., Munk R., Kundu G., De S., Abdelmohsen K., Gorospe M. Methods for Analysis of Circular RNAs. Wiley Interdiscip Rev. RNA. 2020;11:e1566. doi: 10.1002/wrna.1566. PubMed DOI PMC

Chen Y.G., Kim M.V., Chen X., Batista P.J., Aoyama S., Wilusz J.E., Iwasaki A., Chang H.Y. Sensing Self and Foreign Circular RNAs by Intron Identity. Mol. Cell. 2017;67:228–238.e5. doi: 10.1016/j.molcel.2017.05.022. PubMed DOI PMC

Wesselhoeft R.A., Kowalski P.S., Anderson D.G. Engineering Circular RNA for Potent and Stable Translation in Eukaryotic Cells. Nat. Commun. 2018;9:2629. doi: 10.1038/s41467-018-05096-6. PubMed DOI PMC

Meng J., Chen S., Han J., Tan Q., Wang X., Wang H., Zhong W., Qin Y., Qiao K., Zhang C., et al. Derepression of Co-Silenced Tumor Suppressor Genes by Nanoparticle-Loaded Circular ssDNA Reduces Tumor Malignancy. Sci. Transl. Med. 2018;10:eaao6321. doi: 10.1126/scitranslmed.aao6321. PubMed DOI

Piwecka M., Glažar P., Hernandez-Miranda L.R., Memczak S., Wolf S.A., Rybak-Wolf A., Filipchyk A., Klironomos F., Cerda Jara C.A., Fenske P., et al. Loss of a Mammalian Circular RNA Locus Causes miRNA Deregulation and Affects Brain Function. Science. 2017;357:1254. doi: 10.1126/science.aam8526. PubMed DOI

Caldas C., So C.W., MacGregor A., Ford A.M., McDonald B., Chan L.C., Wiedemann L.M. Exon Scrambling of MLL Transcripts Occur Commonly and Mimic Partial Genomic Duplication of the Gene. Gene. 1998;208:167–176. doi: 10.1016/S0378-1119(97)00640-9. PubMed DOI

Memczak S., Papavasileiou P., Peters O., Rajewsky N. Identification and Characterization of Circular RNAs as a New Class of Putative Biomarkers in Human Blood. PLoS ONE. 2015;10:e0141214. doi: 10.1371/journal.pone.0141214. PubMed DOI PMC

Nicolet B.P., Engels S., Aglialoro F., van den Akker E., von Lindern M., Wolkers M.C. Circular RNA Expression in Human Hematopoietic Cells is Widespread and Cell-Type Specific. Nucleic Acids Res. 2018;46:8168–8180. doi: 10.1093/nar/gky721. PubMed DOI PMC

Preußer C., Hung L., Schneider T., Schreiner S., Hardt M., Moebus A., Santoso S., Bindereif A. Selective Release of circRNAs in Platelet-Derived Extracellular Vesicles. J. Extracell. Vesicles. 2018;7:1424473. doi: 10.1080/20013078.2018.1424473. PubMed DOI PMC

Hirsch S., Blätte T.J., Grasedieck S., Cocciardi S., Rouhi A., Jongen-Lavrencic M., Paschka P., Krönke J., Gaidzik V.I., Döhner H., et al. Circular RNAs of the Nucleophosmin (NPM1) Gene in Acute Myeloid Leukemia. Haematologica. 2017;102:2039–2047. doi: 10.3324/haematol.2017.172866. PubMed DOI PMC

Wu D., Wen X., Han X., Wang S., Wang Y., Shen M., Fan S., Zhang Z., Shan Q., Li M., et al. Role of Circular RNA DLEU2 in Human Acute Myeloid Leukemia. Mol. Cell. Biol. 2018;38:e00259-18. doi: 10.1128/MCB.00259-18. PubMed DOI PMC

Chen H., Liu T., Liu J., Feng Y., Wang B., Wang J., Bai J., Zhao W., Shen Y., Wang X., et al. Circ-ANAPC7 is Upregulated in Acute Myeloid Leukemia and Appears to Target the MiR-181 Family. Cell Physiol. Biochem. 2018;47:1998–2007. doi: 10.1159/000491468. PubMed DOI

Fan H., Li Y., Liu C., Liu Y., Bai J., Li W. Circular RNA-100290 Promotes Cell Proliferation and Inhibits Apoptosis in Acute Myeloid Leukemia Cells Via Sponging miR-203. Biochem. Biophys. Res. Commun. 2018;507:178–184. doi: 10.1016/j.bbrc.2018.11.002. PubMed DOI

Zhang Y., Zhou S., Yan H., Xu D., Chen H., Wang X., Wang X., Liu Y., Zhang L., Wang S., et al. miR-203 Inhibits Proliferation and Self-Renewal of Leukemia Stem Cells by Targeting Survivin and Bmi-1. Sci. Rep. 2016;6:19995. doi: 10.1038/srep19995. PubMed DOI PMC

Wu S., Du Y., Beckford J., Alachkar H. Upregulation of the EMT Marker Vimentin is Associated with Poor Clinical Outcome in Acute Myeloid Leukemia. J. Transl. Med. 2018;16:170. doi: 10.1186/s12967-018-1539-y. PubMed DOI PMC

Ping L., Jian-Jun C., Chu-Shu L., Guang-Hua L., Ming Z. Silencing of circ_0009910 Inhibits Acute Myeloid Leukemia Cell Growth through Increasing miR-20a-5p. Blood Cells Mol. Dis. 2019;75:41–47. doi: 10.1016/j.bcmd.2018.12.006. PubMed DOI

Li W., Zhong C., Jiao J., Li P., Cui B., Ji C., Ma D. Characterization of hsa_circ_0004277 as a New Biomarker for Acute Myeloid Leukemia Via Circular RNA Profile and Bioinformatics Analysis. Int. J. Mol. Sci. 2017;18:597. doi: 10.3390/ijms18030597. PubMed DOI PMC

Shang J., Chen W., Wang Z., Wei T., Chen Z., Wu W. CircPAN3 Mediates Drug Resistance in Acute Myeloid Leukemia through the miR-153-5p/miR-183-5p-XIAP Axis. Exp. Hematol. 2019;70:42–54. PubMed

Haferlach T., Nagata Y., Grossmann V., Okuno Y., Bacher U., Nagae G., Schnittger S., Sanada M., Kon A., Alpermann T., et al. Landscape of Genetic Lesions in 944 Patients with Myelodysplastic Syndromes. Leukemia. 2014;28:241–247. doi: 10.1038/leu.2013.336. PubMed DOI PMC

Papaemmanuil E., Gerstung M., Malcovati L., Tauro S., Gundem G., Van Loo P., Yoon C.J., Ellis P., Wedge D.C., Pellagatti A., et al. Clinical and Biological Implications of Driver Mutations in Myelodysplastic Syndromes. Blood. 2013;122:3616–3627. doi: 10.1182/blood-2013-08-518886. PubMed DOI PMC

Armstrong R.N., Steeples V., Singh S., Sanchi A., Boultwood J., Pellagatti A. Splicing Factor Mutations in the Myelodysplastic Syndromes: Target Genes and Therapeutic Approaches. Adv. Biol. Regul. 2018;67:13–29. doi: 10.1016/j.jbior.2017.09.008. PubMed DOI

Joshi P., Halene S., Abdel-Wahab O. How do Messenger RNA Splicing Alterations Drive Myelodysplasia? Blood. 2017;129:2465–2470. doi: 10.1182/blood-2017-02-692715. PubMed DOI PMC

Ramabadran R., Wang J., Guzman A., Cullen S.M., Brunetti L., Gundry M., Chan S., Kyba M., Westbrook T., Goodell M. Loss of De Novo DNA Methyltransferase DNMT3A Impacts Alternative Splicing in Hematopoietic Stem Cells. Blood. 2017;130:1. PubMed

Lord A.M., Clement K., Schneider R.K., Marie M., Chen M.C., Levine R.L., Mullally A., Galili N., Ali A.M., Raza A., et al. Loss of TET2 Function in Myelodysplastic Syndrome Results in Intragenic Hypermethylation and Alterations in mRNA Splicing. Blood. 2014;124:775. doi: 10.1182/blood.V124.21.775.775. DOI

Liang D., Tatomer D.C., Luo Z., Wu H., Yang L., Chen L., Cherry S., Wilusz J.E. The Output of Protein-Coding Genes Shifts to Circular RNAs when the Pre-mRNA Processing Machinery is Limiting. Mol. Cell. 2017;68:940–954. doi: 10.1016/j.molcel.2017.10.034. PubMed DOI PMC