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Squaring the circle: circRNAs in melanoma

Abstract

Non-coding RNAs are emerging as critical molecules in the genesis, progression, and therapy resistance of cutaneous melanoma. This includes circular RNAs (circRNAs), a class of non-coding RNAs with distinct characteristics that forms through non-canonical back-splicing. In this review, we summarize the features and functions of circRNAs and introduce the current knowledge of the roles of circRNAs in melanoma. We also highlight the various mechanisms of action of the well-studied circRNA CDR1as and describe how it acts as a melanoma tumor suppressor. We further discuss the utility of circRNAs as biomarkers, therapeutic targets, and therapeutic agents in melanoma and outline challenges that must be overcome to comprehensively characterize circRNA functions.

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Fig. 1: The many functions of CDR1as.

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Gregory J. Goodall & Vihandha O. Wickramasinghe

References

  1. Alexandrov LB, Nik-Zainal S, Wedge DC, Aparicio SAJR, Behjati S, Biankin AV. et al. Signatures of mutational processes in human cancer. Nature. 2013;500:415–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Hayward NK, Wilmott JS, Waddell N, Johansson PA, Field MA, Nones K, et al. Whole-genome landscapes of major melanoma subtypes. Nature. 2017;545:175–80.

    Article  CAS  PubMed  Google Scholar 

  3. Shain AH, Joseph NM, Yu R, Benhamida J, Liu S, Prow T, et al. Genomic and transcriptomic analysis reveals incremental disruption of key signaling pathways during melanoma evolution. Cancer cell. 2018;34:45–55. e4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Shain AH, Yeh I, Kovalyshyn I, Sriharan A, Talevich E, Gagnon A, et al. The genetic evolution of melanoma from precursor lesions. N Engl J Med. 2015;373:1926–36.

    Article  PubMed  CAS  Google Scholar 

  5. The CGAN. Genomic classification of cutaneous melanoma. Cell. 2015;161:1681–96.

    Article  CAS  Google Scholar 

  6. Pollock PM, Harper UL, Hansen KS, Yudt LM, Stark M, Robbins CM, et al. High frequency of BRAF mutations in nevi. Nat Genet. 2003;33:19–20.

    Article  CAS  PubMed  Google Scholar 

  7. Turner N, Ware O, Bosenberg M. Genetics of metastasis: melanoma and other cancers. Clin Exp Metastasis. 2018;35:379–91.

    Article  CAS  PubMed  Google Scholar 

  8. Vergara IA, Mintoff CP, Sandhu S, McIntosh L, Young RJ, Wong SQ, et al. Evolution of late-stage metastatic melanoma is dominated by aneuploidy and whole genome doubling. Nat Commun. 2021;12:1434.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Rambow F, Marine J-C, Goding CR. Melanoma plasticity and phenotypic diversity: therapeutic barriers and opportunities. Gene Dev. 2019;33:1295–318.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Sarkar D, Leung EY, Baguley BC, Finlay GJ, Askarian-Amiri ME. Epigenetic regulation in human melanoma: past and future. Epigenetics. 2015;10:103–21.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Vera O, Jasani N, Karreth FA. Long non-coding RNAs in melanoma development and biology. Proc Singap Natl Acad Sci. 2020;14:145–66.

    Article  Google Scholar 

  12. Leucci E, Vendramin R, Spinazzi M, Laurette P, Fiers M, Wouters J, et al. Melanoma addiction to the long non-coding RNA SAMMSON. Nature. 2016;531:518–22.

    Article  CAS  PubMed  Google Scholar 

  13. Vendramin R, Verheyden Y, Ishikawa H, Goedert L, Nicolas E, Saraf K, et al. SAMMSON fosters cancer cell fitness by concertedly enhancing mitochondrial and cytosolic translation. Nat Struct Mol Biol. 2018;25:1035–46.

    Article  CAS  PubMed  Google Scholar 

  14. Vera O, Bok I, Jasani N, Nakamura K, Xu X, Mecozzi N, et al. A MAPK/miR-29 axis suppresses melanoma by targeting MAFG and MYBL2. Cancers. 2021;13:1408.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chen L-L. The expanding regulatory mechanisms and cellular functions of circular RNAs. Nat Rev Mol Cell Bio. 2020;21:475–90.

    Article  CAS  Google Scholar 

  16. Xiao M-S, Ai Y, Wilusz JE. Biogenesis and functions of circular RNAs come into focus. Trends Cell Biol. 2020;30:226–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chen L-L, Yang L. Regulation of circRNA biogenesis. Rna Biol. 2015;12:381–8.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, et al. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014;56:55–66.

    Article  CAS  PubMed  Google Scholar 

  19. Conn SJ, Pillman KA, Toubia J, Conn VM, Salmanidis M, Phillips CA, et al. The RNA binding protein quaking regulates formation of circRNAs. Cell. 2015;160:1125–34.

    Article  CAS  PubMed  Google Scholar 

  20. Errichelli L, Modigliani SD, Laneve P, Colantoni A, Legnini I, Capauto D, et al. FUS affects circular RNA expression in murine embryonic stem cell-derived motor neurons. Nat Commun. 2017;8:14741.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Ivanov A, Memczak S, Wyler E, Torti F, Porath HT, Orejuela MR, et al. Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep. 2015;10:170–7.

    Article  CAS  PubMed  Google Scholar 

  22. Nemlich Y, Greenberg E, Ortenberg R, Besser MJ, Barshack I, Jacob-Hirsch J, et al. MicroRNA-mediated loss of ADAR1 in metastatic melanoma promotes tumor growth. J Clin Invest. 2013;123:2703–18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Liang D, Tatomer DC, Luo Z, Wu H, Yang L, Chen L-L, et al. The output of protein-coding genes shifts to circular RNAs when the pre-mRNA processing machinery is limiting. Mol Cell. 2017;68:940–54. e3

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Guo JU, Agarwal V, Guo H, Bartel DP. Expanded identification and characterization of mammalian circular RNAs. Genome Biol. 2014;15:409.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2013;19:141–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495:333–8.

    Article  CAS  PubMed  Google Scholar 

  27. Rybak-Wolf A, Stottmeister C, Glažar P, Jens M, Pino N, Giusti S, et al. Circular RNAs in the mammalian brain are highly abundant, conserved, and dynamically expressed. Mol Cell. 2015;58:870–85.

    Article  CAS  PubMed  Google Scholar 

  28. Salzman J, Gawad C, Wang PL, Lacayo N, Brown PO. Circular RNAs are the predominant transcript isoform from hundreds of human genes in diverse cell types. PloS one. 2012;7:e30733.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Salzman J, Chen RE, Olsen MN, Wang PL, Brown PO. Cell-type specific features of circular RNA expression. PLoS Genet. 2013;9:e1003777.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Szabo L, Morey R, Palpant NJ, Wang PL, Afari N, Jiang C, et al. Statistically based splicing detection reveals neural enrichment and tissue-specific induction of circular RNA during human fetal development. Genome Biol. 2015;16:126.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Venø MT, Hansen TB, Venø ST, Clausen BH, Grebing M, Finsen B, et al. Spatio-temporal regulation of circular RNA expression during porcine embryonic brain development. Genome Biol. 2015;16:245.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Westholm JO, Miura P, Olson S, Shenker S, Joseph B, Sanfilippo P, et al. Genome-wide analysis of drosophila circular RNAs reveals their structural and sequence properties and age-dependent neural accumulation. Cell Rep. 2014;9:1966–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. You X, Vlatkovic I, Babic A, Will T, Epstein I, Tushev G, et al. Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci. 2015;18:603–10.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495:384–8.

    Article  CAS  PubMed  Google Scholar 

  35. Capel B, Swain A, Nicolis S, Hacker A, Walter M, Koopman P, et al. Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell. 1993;73:1019–30.

    Article  CAS  PubMed  Google Scholar 

  36. Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP. A ceRNA hypothesis: the Rosetta Stone of a hidden RNA language? Cell. 2011;146:353–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Karreth FA, Pandolfi PP. ceRNA cross-talk in cancer: when ce-bling rivalries go awry. Cancer Discov. 2013;3:1113–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Du WW, Fang L, Yang W, Wu N, Awan FM, Yang Z, et al. Induction of tumor apoptosis through a circular RNA enhancing Foxo3 activity. Cell Death Differ. 2017;24:357–70.

    Article  CAS  PubMed  Google Scholar 

  39. Du WW, Yang W, Liu E, Yang Z, Dhaliwal P, Yang BB. Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res. 2016;44:2846–58.

    Article  PubMed  PubMed Central  Google Scholar 

  40. Holdt LM, Stahringer A, Sass K, Pichler G, Kulak NA, Wilfert W, et al. Circular non-coding RNA ANRIL modulates ribosomal RNA maturation and atherosclerosis in humans. Nat Commun. 2016;7:12429.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Abdelmohsen K, Panda AC, Munk R, Grammatikakis I, Dudekula DB, De S, et al. Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1. Rna Biol. 2017;14:361–9.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Yang Q, Du WW, Wu N, Yang W, Awan FM, Fang L, et al. A circular RNA promotes tumorigenesis by inducing c-myc nuclear translocation. Cell Death Differ. 2017;24:1609–20.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Yang Z-G, Awan FM, Du WW, Zeng Y, Lyu J, Wu D, et al. The circular RNA interacts with STAT3, increasing its nuclear translocation and wound repair by modulating Dnmt3a and miR-17 function. Mol Ther: J Am Soc Gene Ther. 2017;25:2062–74.

    Article  CAS  Google Scholar 

  44. Li Z, Huang C, Bao C, Chen L, Lin M, Wang X, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 2015;22:256–64.

    Article  PubMed  CAS  Google Scholar 

  45. Zhang Y, Zhang X-O, Chen T, Xiang J-F, Yin Q-F, Xing Y-H, et al. Circular intronic long noncoding RNAs. Mol Cell. 2013;51:792–806.

    Article  CAS  PubMed  Google Scholar 

  46. Conn VM, Hugouvieux V, Nayak A, Conos SA, Capovilla G, Cildir G, et al. A circRNA from SEPALLATA3 regulates splicing of its cognate mRNA through R-loop formation. Nat Plants. 2017;3:17053.

    Article  CAS  PubMed  Google Scholar 

  47. Wang Y, Wang Z. Efficient backsplicing produces translatable circular mRNAs. Rna. 2015;21:172–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Pamudurti NR, Bartok O, Jens M, Ashwal-Fluss R, Stottmeister C, Ruhe L, et al. Translation of CircRNAs. Mol cell. 2017;66:9–21. e7

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Yang Y, Fan X, Mao M, Song X, Wu P, Zhang Y, et al. Extensive translation of circular RNAs driven by N6-methyladenosine. Cell Res. 2017;27:626–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Begum S, Yiu A, Stebbing J, Castellano L. Novel tumour suppressive protein encoded by circular RNA, circ-SHPRH, in glioblastomas. Oncogene. 2018;37:4055–7.

    Article  CAS  PubMed  Google Scholar 

  51. Zhang M, Huang N, Yang X, Luo J, Yan S, Xiao F, et al. A novel protein encoded by the circular form of the SHPRH gene suppresses glioma tumorigenesis. Oncogene. 2018;37:1805–14.

    Article  CAS  PubMed  Google Scholar 

  52. Liang W-C, Wong C-W, Liang P-P, Shi M, Cao Y, Rao S-T, et al. Translation of the circular RNA circβ-catenin promotes liver cancer cell growth through activation of the Wnt pathway. Genome Biol. 2019;20:84.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Yang Y, Gao X, Zhang M, Yan S, Sun C, Xiao F, et al. Novel role of FBXW7 circular RNA in repressing glioma tumorigenesis. J Natl Cancer Inst. 2017;110:304–15.

    Article  PubMed Central  CAS  Google Scholar 

  54. Zheng X, Chen L, Zhou Y, Wang Q, Zheng Z, Xu B, et al. A novel protein encoded by a circular RNA circPPP1R12A promotes tumor pathogenesis and metastasis of colon cancer via Hippo-YAP signaling. Mol Cancer. 2019;18:47.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Zhang M, Zhao K, Xu X, Yang Y, Yan S, Wei P, et al. A peptide encoded by circular form of LINC-PINT suppresses oncogenic transcriptional elongation in glioblastoma. Nat Commun. 2018;9:4475.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  56. Legnini I, Timoteo GD, Rossi F, Morlando M, Briganti F, Sthandier O, et al. Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis. Mol Cell. 2017;66:22–37. e9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Ho-Xuan H, Glažar P, Latini C, Heizler K, Haase J, Hett R, et al. Comprehensive analysis of translation from overexpressed circular RNAs reveals pervasive translation from linear transcripts. Nucleic Acids Res. 2020;48:gkaa704.

    Article  CAS  Google Scholar 

  58. Hansen TB, Wiklund ED, Bramsen JB, Villadsen SB, Statham AL, Clark SJ, et al. miRNA‐dependent gene silencing involving Ago2‐mediated cleavage of a circular antisense RNA. Embo J. 2011;30:4414–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Barrett SP, Parker KR, Horn C, Mata M, Salzman J. ciRS-7 exonic sequence is embedded in a long non-coding RNA locus. Plos Genet. 2017;13:e1007114.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Hanniford D, Ulloa-Morales A, Karz A, Berzoti-Coelho MG, Moubarak RS, Sánchez-Sendra B, et al. Epigenetic silencing of CDR1as drives IGF2BP3-mediated melanoma invasion and metastasis. Cancer Cell. 2020;37:55–70. e15

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Kristensen LS, Ebbesen KK, Sokol M, Jakobsen T, Korsgaard U, Eriksen AC, et al. Spatial expression analyses of the putative oncogene ciRS-7 in cancer reshape the microRNA sponge theory. Nat Commun. 2020;11:4551.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Yoshimoto R, Rahimi K, Hansen TB, Kjems J, Mayeda A. Biosynthesis of circular RNA ciRS-7/CDR1as is mediated by mammalian-wide interspersed repeats. Iscience. 2020;23:101345.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Piwecka M, Glažar P, Hernandez-Miranda LR, Memczak S, Wolf SA, Rybak-Wolf A, et al. Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science. 2017;8:eaam8526.

    Article  CAS  Google Scholar 

  64. Giles KM, Brown RAM, Ganda C, Podgorny MJ, Candy PA, Wintle LC, et al. microRNA-7-5p inhibits melanoma cell proliferation and metastasis by suppressing RelA/NF-κB. Oncotarget. 2016;7:31663–80.

    Article  PubMed  PubMed Central  Google Scholar 

  65. Giles KM, Brown RAM, Epis MR, Kalinowski FC, Leedman PJ. miRNA-7-5p inhibits melanoma cell migration and invasion. Biochem Bioph Res Co. 2013;430:706–10.

    Article  CAS  Google Scholar 

  66. Horsham JL, Kalinowski FC, Epis MR, Ganda C, Brown RAM, Leedman PJ. Clinical potential of microRNA-7 in cancer. J Clin Med. 2015;4:1668–87.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  67. Tang W, Ji M, He G, Yang L, Niu Z, Jian M, et al. Silencing CDR1as inhibits colorectal cancer progression through regulating microRNA-7. Oncotargets Ther. 2017;10:2045–56.

    Article  CAS  Google Scholar 

  68. Xu L, Zhang M, Zheng X, Yi P, Lan C, Xu M. The circular RNA ciRS-7 (Cdr1as) acts as a risk factor of hepatic microvascular invasion in hepatocellular carcinoma. J Cancer Res Clin. 2017;143:17–27.

    Article  CAS  Google Scholar 

  69. Zhong Q, Huang J, Wei J, Wu R. Circular RNA CDR1as sponges miR-7-5p to enhance E2F3 stability and promote the growth of nasopharyngeal carcinoma. Cancer Cell Int. 2019;19:252.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  70. Ulitsky I, Shkumatava A, Jan CH, Sive H, Bartel DP. Conserved function of lincRNAs in vertebrate embryonic development despite rapid sequence evolution. Cell. 2012;151:684–6.

    Article  CAS  Google Scholar 

  71. Kleaveland B, Shi CY, Stefano J, Bartel DP. A network of noncoding regulatory RNAs acts in the mammalian brain. Cell. 2018;174:350–62. e17

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  72. Lou J, Hao Y, Lin K, Lyu Y, Chen M, Wang H, et al. Circular RNA CDR1as disrupts the p53/MDM2 complex to inhibit Gliomagenesis. Mol Cancer. 2020;19:138.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Li P, Yang X, Yuan W, Yang C, Zhang X, Han J, et al. CircRNA-Cdr1as exerts anti-oncogenic functions in bladder cancer by sponging MicroRNA-135a. Cell Physiol Biochem. 2018;46:1606–16.

    Article  CAS  PubMed  Google Scholar 

  74. Chen H, Mao M, Jiang J, Zhu D, Li P. Circular RNA CDR1as acts as a sponge of miR-135b-5p to suppress ovarian cancer progression. Oncotargets Ther. 2019;12:3869–79.

    Article  CAS  Google Scholar 

  75. Ren J-W, Li Z-J, Tu C. MiR-135 post-transcriptionally regulates FOXO1 expression and promotes cell proliferation in human malignant melanoma cells. Int J Clin Exp Patho. 2015;8:6356–66.

    Google Scholar 

  76. Hu Y, Wang Q, Zhu X. MiR-135b is a novel oncogenic factor in cutaneous melanoma by targeting LATS2. Melanoma Res. 2018;29:119–25.

    Article  CAS  Google Scholar 

  77. Zhang X-H, Xin Z-M. MiR-135b-5p inhibits the progression of malignant melanoma cells by targeting RBX1. Eur Rev Med Pharm. 2020;24:1309–15.

    Google Scholar 

  78. Wang Q, Chen J, Wang A, Sun L, Qian L, Zhou X, et al. Differentially expressed circRNAs in melanocytes and melanoma cells and their effect on cell proliferation and invasion. Oncol Rep. 2018;39:1813–24.

    CAS  PubMed  Google Scholar 

  79. Lu R, Zhang X, Li X, Wan X. Circ_0016418 promotes melanoma development and glutamine catabolism by regulating the miR-605-5p/GLS axis. Int J Clin Exp Pathol. 2020;13:1791–801.

    PubMed  PubMed Central  Google Scholar 

  80. Zou Y, Wang S-S, Wang J, Su H-L, Xu J-H. CircRNA_0016418 expedites the progression of human skin melanoma via miR-625/YY1 axis. Eur Rev Med Pharm. 2019;23:10918–30.

    CAS  Google Scholar 

  81. Chen Z, Chen J, Wa Q, He M, Wang X, Zhou J, et al. Knockdown of circ_0084043 suppresses the development of human melanoma cells through miR-429/tribbles homolog 2 axis and Wnt/β-catenin pathway. Life Sci. 2020;243:117323.

    Article  CAS  PubMed  Google Scholar 

  82. Luan W, Shi Y, Zhou Z, Xia Y, Wang J. circRNA_0084043 promote malignant melanoma progression via miR-153-3p/Snail axis. Biochem Bioph Res Co. 2018;502:22–29.

    Article  CAS  Google Scholar 

  83. Bian D, Wu Y, Song G. Novel circular RNA, hsa_circ_0025039 promotes cell growth, invasion and glucose metabolism in malignant melanoma via the miR-198/CDK4 axis. Biomed Pharmacother. 2018;108:165–76.

    Article  CAS  PubMed  Google Scholar 

  84. Tian S, Han G, Lu L, Meng X. Circ-FOXM1 contributes to cell proliferation, invasion, and glycolysis and represses apoptosis in melanoma by regulating miR-143-3p/FLOT2 axis. World J Surg Oncol. 2020;18:56.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Qian P, Linbo L, Xiaomei Z, Hui P. Circ_0002770, acting as a competitive endogenous RNA, promotes proliferation and invasion by targeting miR-331-3p in melanoma. Cell Death Dis. 2020;11:264.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Wei C-Y, Zhu M-X, Lu N-H, Liu J-Q, Yang Y-W, Zhang Y, et al. Circular RNA circ_0020710 drives tumor progression and immune evasion by regulating the miR-370-3p/CXCL12 axis in melanoma. Mol Cancer. 2020;19:84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Yin D, Wei G, Yang F, Sun X. Circular RNA has circ 0001591 promoted cell proliferation and metastasis of human melanoma via ROCK1/PI3K/AKT by targeting miR-431-5p. Hum Exp Toxicol. 2021;40:310–24.

    Article  CAS  PubMed  Google Scholar 

  88. Lu J, Li Y. Circ_0079593 facilitates proliferation, metastasis, glucose metabolism and inhibits apoptosis in melanoma by regulating the miR-516b/GRM3 axis. Mol Cell Biochem. 2020;475:227–37.

    Article  CAS  PubMed  Google Scholar 

  89. Jin C, Dong D, Yang Z, Xia R, Tao S, Piao M. CircMYC regulates glycolysis and cell proliferation in melanoma. Cell Biochem Biophys. 2020;78:77–88.

    Article  CAS  PubMed  Google Scholar 

  90. Chen J, Zhou X, Yang J, Sun Q, Liu Y, Li N, et al. Circ-GLI1 promotes metastasis in melanoma through interacting with p70S6K2 to activate Hedgehog/GLI1 and Wnt/β-catenin pathways and upregulate Cyr61. Cell Death Dis. 2020;11:596.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Fang L, Du WW, Awan FM, Dong J, Yang BB. The circular RNA circ-Ccnb1 dissociates Ccnb1/Cdk1 complex suppressing cell invasion and tumorigenesis. Cancer Lett. 2019;459:216–26.

    Article  CAS  PubMed  Google Scholar 

  92. Lin Q, Jiang H, Lin D. Circular RNA ITCH downregulates GLUT1 and suppresses glucose uptake in melanoma to inhibit cancer cell proliferation. J Dermatol Treat. 2019;32:1–16.

    CAS  Google Scholar 

  93. Kramer MC, Liang D, Tatomer DC, Gold B, March ZM, Cherry S, et al. Combinatorial control of Drosophila circular RNA expression by intronic repeats, hnRNPs, and SR proteins. Genes Dev. 2015;29:2168–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Mecozzi N, Nenci A, Vera O, Falzone A, DeNicola GM, Karreth FA. Genetic tools for the stable overexpression of circular RNAs. Biorxiv 2021. https://doi.org/10.1101/2021.05.27.446018.

  95. Zhang Y, Nguyen TM, Zhang X-O, Wang L, Phan T, Clohessy JG, et al. Optimized RNA-targeting CRISPR/Cas13d technology outperforms shRNA in identifying functional circRNAs. Genome Biol. 2021;22:41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Li Y, Zheng Q, Bao C, Li S, Guo W, Zhao J, et al. Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res. 2015;25:981–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Lasda E, Parker R. Circular RNAs co-precipitate with extracellular vesicles: a possible mechanism for circRNA clearance. Plos One. 2016;11:e0148407.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  98. Chen Y, Bathula SR, Yang Q, Huang L. Targeted nanoparticles deliver siRNA to melanoma. J Invest Dermatol. 2010;130:2790–8.

    Article  CAS  PubMed  Google Scholar 

  99. Fattore L, Campani V, Ruggiero CF, Salvati V, Liguoro D, Scotti L, et al. In vitro biophysical and biological characterization of lipid nanoparticles co-encapsulating oncosuppressors mir-199b-5p and mir-204-5p as potentiators of target therapy in metastatic melanoma. Int J Mol Sci. 2020;21:1930.

    Article  CAS  PubMed Central  Google Scholar 

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Acknowledgements

This work was supported by grants from the NCI/NIH (R01 CA259046) and the Harry J. Lloyd Charitable Foundation to FAK.

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NM and FAK devised the conceptual idea of the article. NM wrote the manuscript with input from OV and FAK.

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Correspondence to Florian A. Karreth.

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Mecozzi, N., Vera, O. & Karreth, F.A. Squaring the circle: circRNAs in melanoma. Oncogene 40, 5559–5566 (2021). https://doi.org/10.1038/s41388-021-01977-1

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