REFERENCES
1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71:209-49.
2. Yang JD, Hainaut P, Gores GJ, Amadou A, Plymoth A, Roberts LR. A global view of hepatocellular carcinoma: trends, risk, prevention and management. Nat Rev Gastroenterol Hepatol. 2019;16:589-604.
3. Omata M, Cheng AL, Kokudo N, et al. Asia-Pacific clinical practice guidelines on the management of hepatocellular carcinoma: a 2017 update. Hepatol Int. 2017;11:317-70.
4. Tian Y, Zhang M, Liu LX, et al. Exploring non-coding RNA mechanisms in hepatocellular carcinoma: implications for therapy and prognosis. Front Immunol. 2024;15:1400744.
5. Project Consortium. An integrated encyclopedia of DNA elements in the human genome. Nature. 2012;489:57-74.
6. Mercer TR, Dinger ME, Mattick JS. Long non-coding RNAs: insights into functions. Nat Rev Genet. 2009;10:155-9.
7. Glažar P, Papavasileiou P, Rajewsky N. circBase: a database for circular RNAs. RNA. 2014;20:1666-70.
8. Sanger HL, Klotz G, Riesner D, Gross HJ, Kleinschmidt AK. 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;73:3852-6.
9. Capel B, Swain A, Nicolis S, et al. Circular transcripts of the testis-determining gene Sry in adult mouse testis. Cell. 1993;73:1019-30.
10. Chen CK, Cheng R, Demeter J, et al. Structured elements drive extensive circular RNA translation. Mol Cell. 2021;81:4300-18.e13.
12. Fan X, Zhang X, Wu X, et al. Single-cell RNA-seq transcriptome analysis of linear and circular RNAs in mouse preimplantation embryos. Genome Biol. 2015;16:148.
13. Memczak S, Jens M, Elefsinioti A, et al. Circular RNAs are a large class of animal RNAs with regulatory potency. Nature. 2013;495:333-8.
14. Hsu MT, Coca-Prados M. Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells. Nature. 1979;280:339-40.
16. 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.
17. Enuka Y, Lauriola M, Feldman ME, 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;44:1370-83.
18. Huang K, Li N, Li Y, et al. Delivery of circular mRNA via degradable lipid nanoparticles against SARS-CoV-2 delta variant. bioRxiv 2022;bioRxiv:2022.05.12.491597.
19. Qu L, Yi Z, Shen Y, et al. Circular RNA vaccines against SARS-CoV-2 and emerging variants. Cell. 2022;185:1728-44.e16.
20. Li H, Li K, Lai W, et al. Comprehensive circular RNA profiles in plasma reveals that circular RNAs can be used as novel biomarkers for systemic lupus erythematosus. Clin Chim Acta. 2018;480:17-25.
21. 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.
22. Vo JN, Cieslik M, Zhang Y, et al. The landscape of circular RNA in cancer. Cell. 2019;176:869-81.e13.
23. Bahn JH, Zhang Q, Li F, et al. The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva. Clin Chem. 2015;61:221-30.
24. Maass PG, Glažar P, Memczak S, et al. A map of human circular RNAs in clinically relevant tissues. J Mol Med. 2017;95:1179-89.
25. Preußer C, Hung LH, Schneider T, et al. Selective release of circRNAs in platelet-derived extracellular vesicles. J Extracell Vesicles. 2018;7:1424473.
26. Zhao X, Cai Y, Xu J. Circular RNAs: biogenesis, mechanism, and function in human cancers. Int J Mol Sci. 2019;20:3926.
27. Lee Y, Rio DC. Mechanisms and regulation of alternative pre-mRNA splicing. Annu Rev Biochem. 2015;84:291-323.
28. Jeck WR, Sorrentino JA, Wang K, et al. Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA. 2013;19:141-57.
29. Ivanov A, Memczak S, Wyler E, et al. Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep. 2015;10:170-7.
30. Conn SJ, Pillman KA, Toubia J, et al. The RNA binding protein quaking regulates formation of circRNAs. Cell. 2015;160:1125-34.
31. Fei T, Chen Y, Xiao T, et al. Genome-wide CRISPR screen identifies HNRNPL as a prostate cancer dependency regulating RNA splicing. Proc Natl Acad Sci U S A. 2017;114:E5207-15.
32. 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;8:14741.
33. Ashwal-Fluss R, Meyer M, Pamudurti NR, et al. circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014;56:55-66.
34. Shi L, Yan P, Liang Y, et al. Circular RNA expression is suppressed by androgen receptor (AR)-regulated adenosine deaminase that acts on RNA (ADAR1) in human hepatocellular carcinoma. Cell Death Dis. 2017;8:e3171.
35. Chen Q, Wang H, Li Z, et al. Circular RNA ACTN4 promotes intrahepatic cholangiocarcinoma progression by recruiting YBX1 to initiate FZD7 transcription. J Hepatol. 2022;76:135-47.
36. Zhang Y, Zhang XO, Chen T, et al. Circular intronic long noncoding RNAs. Mol Cell. 2013;51:792-806.
37. Li Z, Huang C, Bao C, et al. Exon-intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol. 2015;22:256-64.
38. Broderick JA, Zamore PD. Competitive endogenous RNAs cannot alter microRNA function in vivo. Mol Cell. 2014;54:711-3.
39. Fei D, Wang F, Wang Y, et al. Circular RNA ACVR2A promotes the progression of hepatocellular carcinoma through mir-511-5p targeting PI3K-Akt signaling pathway. Mol Cancer. 2024;23:159.
40. Tian Y, Han W, Lv K, Fu L, Zhou X. CircSNX6 promotes proliferation, metastasis, and angiogenesis in hepatocellular carcinoma via miR-383-5p/VEGFA signaling pathway. Sci Rep. 2024;14:8243.
41. Liang WC, Wong CW, Liang PP, 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.
42. Li H, Su B, Jiang Y, et al. Circular RNA circDCUN1D4 suppresses hepatocellular carcinoma development via targeting the miR-590-5p/ TIMP3 axis. Mol Cancer. 2025;24:95.
43. Xu J, Ji L, Liang Y, et al. CircRNA-SORE mediates sorafenib resistance in hepatocellular carcinoma by stabilizing YBX1. Signal Transduct Target Ther. 2020;5:298.
44. Huang XY, Huang ZL, Zhang PB, et al. CircRNA-100338 is associated with mTOR signaling pathway and poor prognosis in hepatocellular carcinoma. Front Oncol. 2019;9:392.
45. Huang XY, Huang ZL, Huang J, et al. Exosomal circRNA-100338 promotes hepatocellular carcinoma metastasis via enhancing invasiveness and angiogenesis. J Exp Clin Cancer Res. 2020;39:20.
46. Yu J, Xu QG, Wang ZG, et al. Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma. J Hepatol. 2018;68:1214-27.
47. Wang L, Long H, Zheng Q, Bo X, Xiao X, Li B. Circular RNA circRHOT1 promotes hepatocellular carcinoma progression by initiation of NR2F6 expression. Mol Cancer. 2019;18:119.
48. Huang XY, Zhang PF, Wei CY, et al. Circular RNA circMET drives immunosuppression and anti-PD1 therapy resistance in hepatocellular carcinoma via the miR-30-5p/snail/DPP4 axis. Mol Cancer. 2020;19:92.
49. Zhao J, Zhang T, Wu P, et al. circRNA-0015004 act as a ceRNA to promote RCC2 expression in hepatocellular carcinoma. Sci Rep. 2024;14:16913.
50. Chen G, Shi Y, Liu M, Sun J. circHIPK3 regulates cell proliferation and migration by sponging miR-124 and regulating AQP3 expression in hepatocellular carcinoma. Cell Death Dis. 2018;9:175.
51. Wei Y, Chen X, Liang C, et al. A noncoding regulatory RNAs network driven by circ-CDYL acts specifically in the early stages hepatocellular carcinoma. Hepatology. 2020;71:130-47.
52. Hu ZQ, Zhou SL, Li J, et al. Circular RNA sequencing identifies circASAP1 as a key regulator in hepatocellular carcinoma metastasis. Hepatology. 2020;72:906-22.
53. Sun C, Li G, Liu M. A novel circular RNA, circ_0005394, predicts unfavorable prognosis and contributes to hepatocellular carcinoma progression by regulating miR-507/E2F3 and miR-515-5p/CXCL6 signaling pathways. Onco Targets Ther. 2020;13:6171-80.
54. Zhu YJ, Zheng B, Luo GJ, et al. Circular RNAs negatively regulate cancer stem cells by physically binding FMRP against CCAR1 complex in hepatocellular carcinoma. Theranostics. 2019;9:3526-40.
55. Zhang PF, Wei CY, Huang XY, et al. Circular RNA circTRIM33-12 acts as the sponge of MicroRNA-191 to suppress hepatocellular carcinoma progression. Mol Cancer. 2019;18:105.
56. Han D, Li J, Wang H, et al. Circular RNA circMTO1 acts as the sponge of microRNA-9 to suppress hepatocellular carcinoma progression. Hepatology. 2017;66:1151-64.
57. Wang J, Tan Q, Wang W, Yu J. Mechanism of the regulatory effect of overexpression of circMTO1 on proliferation and apoptosis of hepatoma cells via miR-9-5p/NOX4 axis. Cancer Manag Res. 2020;12:3915-25.
58. Li D, Zhang J, Yang J, et al. CircMTO1 suppresses hepatocellular carcinoma progression via the miR-541-5p/ZIC1 axis by regulating Wnt/β-catenin signaling pathway and epithelial-to-mesenchymal transition. Cell Death Dis. 2021;13:12.
59. Zhong L, Wang Y, Cheng Y, et al. Circular RNA circC3P1 suppresses hepatocellular carcinoma growth and metastasis through miR-4641/PCK1 pathway. Biochem Biophys Res Commun. 2018;499:1044-9.
60. Qiu L, Huang Y, Li Z, et al. Circular RNA profiling identifies circADAMTS13 as a miR-484 sponge which suppresses cell proliferation in hepatocellular carcinoma. Mol Oncol. 2019;13:441-55.
61. Li Y, Chen B, Zhao J, et al. HNRNPL circularizes ARHGAP35 to produce an oncogenic protein. Adv Sci (Weinh). 2021;8:2001701.
62. Song R, Ma S, Xu J, et al. A novel polypeptide encoded by the circular RNA ZKSCAN1 suppresses HCC via degradation of mTOR. Mol Cancer. 2023;22:16.
63. Chen S, Cao X, Zhang J, Wu W, Zhang B, Zhao F. circVAMP3 drives CAPRIN1 phase separation and inhibits hepatocellular carcinoma by suppressing c-Myc translation. Adv Sci (Weinh). 2022;9:e2103817.
64. Rossi F, Legnini I, Megiorni F, et al. Circ-ZNF609 regulates G1-S progression in rhabdomyosarcoma. Oncogene. 2019;38:3843-54.
65. Rossi F, Beltran M, Damizia M, et al. Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity. Mol Cell. 2022;82:75-89.e9.
67. He Y, Huang H, Jin L, et al. CircZNF609 enhances hepatocellular carcinoma cell proliferation, metastasis, and stemness by activating the Hedgehog pathway through the regulation of miR-15a-5p/15b-5p and GLI2 expressions. Cell Death Dis. 2020;11:358.
68. Yao H, Liu N, Lin MC, Zheng J. Positive feedback loop between cancer stem cells and angiogenesis in hepatocellular carcinoma. Cancer Lett. 2016;379:213-9.
69. Lu JC, Zhang PF, Huang XY, et al. Amplification of spatially isolated adenosine pathway by tumor-macrophage interaction induces anti-PD1 resistance in hepatocellular carcinoma. J Hematol Oncol. 2021;14:200.
70. Rao G, Peng X, Tian Y, Fu X, Zhang Y. Circular RNAs in hepatocellular carcinoma: biogenesis, function, and pathology. Front Genet. 2023;14:1106665.
72. Hu Z, Chen G, Zhao Y, et al. Exosome-derived circCCAR1 promotes CD8 + T-cell dysfunction and anti-PD1 resistance in hepatocellular carcinoma. Mol Cancer. 2023;22:55.
73. Zhang PF, Gao C, Huang XY, et al. Cancer cell-derived exosomal circUHRF1 induces natural killer cell exhaustion and may cause resistance to anti-PD1 therapy in hepatocellular carcinoma. Mol Cancer. 2020;19:110.
74. Nishikawa H, Sakaguchi S. Regulatory T cells in cancer immunotherapy. Curr Opin Immunol. 2014;27:1-7.
75. Huang M, Huang X, Huang N. Exosomal circGSE1 promotes immune escape of hepatocellular carcinoma by inducing the expansion of regulatory T cells. Cancer Sci. 2022;113:1968-83.
76. Ying F, Chan MSM, Lee TKW. Cancer-associated fibroblasts in hepatocellular carcinoma and cholangiocarcinoma. Cell Mol Gastroenterol Hepatol. 2023;15:985-99.
77. Liu G, Sun J, Yang ZF, et al. Cancer-associated fibroblast-derived CXCL11 modulates hepatocellular carcinoma cell migration and tumor metastasis through the circUBAP2/miR-4756/IFIT1/3 axis. Cell Death Dis. 2021;12:260.
78. Ma YY, He XJ, Wang HJ, et al. Interaction of coagulation factors and tumor-associated macrophages mediates migration and invasion of gastric cancer. Cancer Sci. 2011;102:336-42.
79. Lan J, Sun L, Xu F, et al. M2 macrophage-derived exosomes promote cell migration and invasion in colon cancer. Cancer Res. 2019;79:146-58.
80. Hao X, Sun G, Zhang Y, et al. Targeting immune cells in the tumor microenvironment of HCC: new opportunities and challenges. Front Cell Dev Biol. 2021;9:775462.
81. Wang Y, Gao R, Li J, et al. Downregulation of hsa_circ_0074854 suppresses the migration and invasion in hepatocellular carcinoma via interacting with HuR and via suppressing exosomes-mediated macrophage M2 polarization. Int J Nanomedicine. 2021;16:2803-18.
82. Kudo M, Finn RS, Qin S, et al. Lenvatinib versus sorafenib in first-line treatment of patients with unresectable hepatocellular carcinoma: a randomised phase 3 non-inferiority trial. Lancet. 2018;391:1163-73.
83. Finn RS, Qin S, Ikeda M, et al. Atezolizumab plus bevacizumab in unresectable hepatocellular carcinoma. N Engl J Med. 2020;382:1894-905.
84. Tang W, Chen Z, Zhang W, et al. The mechanisms of sorafenib resistance in hepatocellular carcinoma: theoretical basis and therapeutic aspects. Signal Transduct Target Ther. 2020;5:87.
85. Chang Z, Song Y, Luo F, Yang X, Cai Y, Guo H. Circular RNA SMARCA5 promotes a poor prognosis and radiotherapy resistance for patients with hepatocellular carcinoma. Ann Clin Lab Sci. 2023;53:573-77.
86. Duan J, Cai H, Huang Y, Shi L. SNAI2-induced circMTO1 promotes cell proliferation and inhibits apoptosis through the miR-320b/MCL1 axis in human granulosa-like tumor cells. Front Genet. 2021;12:689916.
87. Zhang X, Zhong B, Zhang W, Wu J, Wang Y. Circular RNA circMTO1 inhibits proliferation of glioblastoma cells via miR-92/WWOX signaling pathway. Med Sci Monit. 2019;25:6454-61.
88. Liu DY, Li Z, Zhang K, et al. Circular RNA CircMTO1 suppressed proliferation and metastasis of osteosarcoma through miR-630/KLF6 axis. Eur Rev Med Pharmacol Sci. 2021;25:86-93.
89. Wang P, Zhou C, Li D, Zhang D, Wei L, Deng Y. circMTO1 sponges microRNA-219a-5p to enhance gallbladder cancer progression via the TGF-β/Smad and EGFR pathways. Oncol Lett. 2021;22:563.
90. Chen M, Ai G, Zhou J, Mao W, Li H, Guo J. circMTO1 promotes tumorigenesis and chemoresistance of cervical cancer via regulating miR-6893. Biomed Pharmacother. 2019;117:109064.
91. Yu N, Gong H, Chen W, Peng W. CircRNA ZKSCAN1 promotes lung adenocarcinoma progression by miR-185-5p/TAGLN2 axis. Thorac Cancer. 2023;14:1467-76.
92. Hutvágner G, Zamore PD. A microRNA in a multiple-turnover RNAi enzyme complex. Science. 2002;297:2056-60.
93. Imanishi S, Nagata S, Fujita T, Fujii H. Circular RNAs hsa_circ_0001438 and hsa_circ_0000417 are downregulated and upregulated, respectively, in hepatocellular carcinoma. Int J Exp Pathol. 2022;103:245-51.
94. Wang Z, Deng C, Zheng Y. Involvement of circRNAs in proinflammatory cytokines-mediated β-Cell dysfunction. Mediators Inflamm. 2021;2021:5566453.
95. Yuan X, Mao Y, Ou S. Diagnostic accuracy of circulating exosomal circRNAs in malignances: a meta-analysis and systematic review. Medicine (Baltimore). 2023;102:e33872.
96. Wang M, Yang Y, Xu J, Bai W, Ren X, Wu H. CircRNAs as biomarkers of cancer: a meta-analysis. BMC Cancer. 2018;18:303.
97. Nie G, Peng D, Li B, et al. Diagnostic accuracy of serum/plasma circular RNAs and the combination of circular RNAs and α-fetoprotein for detecting hepatocellular carcinoma: a meta-analysis. Front Genet. 2021;12:722208.
98. Bedair HM, El-Banna EA, Ahmed EA, et al. Evaluation of circular RNA SMARCA5 as a novel biomarker for hepatocellular carcinoma. Asian Pac J Cancer Prev. 2024;25:1411-7.
99. Ji Y, Yang S, Yan X, et al. CircCRIM1 promotes hepatocellular carcinoma proliferation and angiogenesis by sponging miR-378a-3p and regulating SKP2 expression. Front Cell Dev Biol. 2021;9:796686.
100. Feng Y, Liang L, Jia W, et al. Circ_0007386 promotes the progression of hepatocellular carcinoma through the miR-507/ CCNT2 axis. J Hepatocell Carcinoma. 2024;11:1095-112.
101. Li ZD, Li YL, Lu J, Liang S, Zhang C, Zeng LH. Recent research progress of circular RNAs in hepatocellular carcinoma. Front Oncol. 2024;13:1192386.
102. Tang Y, Yuan F, Cao M, et al. CircRNA-mTOR promotes hepatocellular carcinoma progression and lenvatinib resistance through the PSIP1/c-Myc axis. Adv Sci (Weinh). 2025;12:e2410591.
103. Orna Therapeutics. Merck and orna therapeutics collaborate to advance Orna’s next generation of RNA technology. Available from: https://www.ornatx.com/merck-and-orna-therapeutics-collaborate-to-advance-ornas-next-generation-of-rna-technology%ef%bf%bc/. [Last accessed on 17 Jun 2025].
104. Jost I, Shalamova LA, Gerresheim GK, Niepmann M, Bindereif A, Rossbach O. Functional sequestration of microRNA-122 from hepatitis C Virus by circular RNA sponges. RNA Biol. 2018;15:1032-9.
105. Niu D, Wu Y, Lian J. Circular RNA vaccine in disease prevention and treatment. Signal Transduct Target Ther. 2023;8:341.
106. Xie J, Ye F, Deng X, et al. Circular RNA: a promising new star of vaccine. J Transl Int Med. 2023;11:372-81.
107. Bu T, Yang Z, Zhao J, Gao Y, Li F, Yang R. Expanding the potential of circular RNA (CircRNA) vaccines: a promising therapeutic approach. Int J Mol Sci. 2025;26:379.
108. Shen H, Liu B, Xu J, et al. Circular RNAs: characteristics, biogenesis, mechanisms and functions in liver cancer. J Hematol Oncol. 2021;14:134.
109. Wang F, Cai G, Wang Y, et al. Circular RNA-based neoantigen vaccine for hepatocellular carcinoma immunotherapy. MedComm. 2024;5:e667.
110. Li H, Peng K, Yang K, et al. Circular RNA cancer vaccines drive immunity in hard-to-treat malignancies. Theranostics. 2022;12:6422-36.
111. Liu CX, Guo SK, Nan F, Xu YF, Yang L, Chen LL. RNA circles with minimized immunogenicity as potent PKR inhibitors. Mol Cell. 2022;82:420-34.e6.
112. Zhang J, Luo Z, Zheng Y, Duan M, Qiu Z, Huang C. CircRNA as an Achilles heel of cancer: characterization, biomarker and therapeutic modalities. J Transl Med. 2024;22:752.
113. Sun D, Lu ZR. Structure and function of cationic and ionizable lipids for nucleic acid delivery. Pharm Res. 2023;40:27-46.
114. Fan N, Chen K, Zhu R, et al. Manganese-coordinated mRNA vaccines with enhanced mRNA expression and immunogenicity induce robust immune responses against SARS-CoV-2 variants. Sci Adv. 2022;8:eabq3500.
115. Chen R, Wang SK, Belk JA, et al. Engineering circular RNA for enhanced protein production. Nat Biotechnol. 2023;41:262-72.
116. Zhang L, Liang D, Chen C, et al. Circular siRNAs for reducing off-target effects and enhancing long-term gene silencing in cells and mice. Mol Ther Nucleic Acids. 2018;10:237-44.
117. Yang J, Zhu J, Sun J, et al. Intratumoral delivered novel circular mRNA encoding cytokines for immune modulation and cancer therapy. Mol Ther Nucleic Acids. 2022;30:184-97.
118. Amiri A, Bagherifar R, Ansari Dezfouli E, Kiaie SH, Jafari R, Ramezani R. Exosomes as bio-inspired nanocarriers for RNA delivery: preparation and applications. J Transl Med. 2022;20:125.
119. Suzuki H, Zuo Y, Wang J, Zhang MQ, Malhotra A, Mayeda A. Characterization of RNase R-digested cellular RNA source that consists of lariat and circular RNAs from pre-mRNA splicing. Nucleic Acids Res. 2006;34:e63.
120. Hansen TB. Improved circRNA identification by combining prediction algorithms. Front Cell Dev Biol. 2018;6:20.
121. Zeng X, Lin W, Guo M, Zou Q. A comprehensive overview and evaluation of circular RNA detection tools. PLoS Comput Biol. 2017;13:e1005420.
122. Jeck WR, Sharpless NE. Detecting and characterizing circular RNAs. Nat Biotechnol. 2014;32:453-61.
123. Yao Z, Luo J, Hu K, et al. ZKSCAN1 gene and its related circular RNA (circZKSCAN1) both inhibit hepatocellular carcinoma cell growth, migration, and invasion but through different signaling pathways. Mol Oncol. 2017;11:422-37.
124. Nielsen AF, Bindereif A, Bozzoni I, et al. Best practice standards for circular RNA research. Nat Methods. 2022;19:1208-20.
125. Zhang XO, Dong R, Zhang Y, et al. Diverse alternative back-splicing and alternative splicing landscape of circular RNAs. Genome Res. 2016;26:1277-87.
126. Szabo L, Salzman J. Detecting circular RNAs: bioinformatic and experimental challenges. Nat Rev Genet. 2016;17:679-92.
127. Liu CX, Chen LL. Circular RNAs: characterization, cellular roles, and applications. Cell. 2022;185:2016-34.
129. Chujo T, Yamazaki T, Kawaguchi T, et al. Unusual semi-extractability as a hallmark of nuclear body-associated architectural noncoding RNAs. EMBO J. 2017;36:1447-62.
130. Wu M, Xu G, Han C, et al. lncRNA SLERT controls phase separation of FC/DFCs to facilitate Pol I transcription. Science. 2021;373:547-55.
131. You X, Vlatkovic I, Babic A, et al. Neural circular RNAs are derived from synaptic genes and regulated by development and plasticity. Nat Neurosci. 2015;18:603-10.
132. Hansen TB, Jensen TI, Clausen BH, et al. Natural RNA circles function as efficient microRNA sponges. Nature. 2013;495:384-8.
133. Li X, Liu CX, Xue W, et al. Coordinated circRNA biogenesis and function with NF90/NF110 in viral infection. Mol Cell. 2017;67:214-27.e7.
134. Liang D, Wilusz JE. Short intronic repeat sequences facilitate circular RNA production. Genes Dev. 2014;28:2233-47.
135. Starke S, Jost I, Rossbach O, et al. Exon circularization requires canonical splice signals. Cell Rep. 2015;10:103-11.
136. Guarnerio J, Zhang Y, Cheloni G, et al. Intragenic antagonistic roles of protein and circRNA in tumorigenesis. Cell Res. 2019;29:628-40.
137. Litke JL, Jaffrey SR. Highly efficient expression of circular RNA aptamers in cells using autocatalytic transcripts. Nat Biotechnol. 2019;37:667-75.
138. Chen S, Huang V, Xu X, et al. Widespread and functional RNA circularization in localized prostate cancer. Cell. 2019;176:831-43.e22.
139. Pamudurti NR, Patop IL, Krishnamoorthy A, Ashwal-Fluss R, Bartok O, Kadener S. An in vivo strategy for knockdown of circular RNAs. Cell Discov. 2020;6:52.
140. Guarnerio J, Bezzi M, Jeong JC, et al. Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations. Cell. 2016;165:289-302.
141. Li S, Li X, Xue W, et al. Screening for functional circular RNAs using the CRISPR-Cas13 system. Nat Methods. 2021;18:51-9.
142. Piwecka M, Glažar P, Hernandez-Miranda LR, et al. Loss of a mammalian circular RNA locus causes miRNA deregulation and affects brain function. Science. 2017;357:eaam8526.
143. Gao X, Ma XK, Li X, et al. Knockout of circRNAs by base editing back-splice sites of circularized exons. Genome Biol. 2022;23:16.
144. Li X, Yang L, Chen LL. The biogenesis, functions, and challenges of circular RNAs. Mol Cell. 2018;71:428-42.
145. Hama Faraj GS, Hussen BM, Abdullah SR, et al. Advanced approaches of the use of circRNAs as a replacement for cancer therapy. Noncoding RNA Res. 2024;9:811-30.
146. Aldén M, Olofsson Falla F, Yang D, et al. Intracellular reverse transcription of Pfizer BioNTech COVID-19 mRNA vaccine BNT162b2 in vitro in human liver cell line. Curr Issues Mol Biol. 2022;44:1115-26.
147. Long J, Yu C, Zhang H, et al. Novel ionizable lipid nanoparticles for SARS-CoV-2 omicron mRNA delivery. Adv Healthc Mater. 2023;12:e2202590.
148. Alqahtani S, Alqahtani T, Venkatesan K, et al. Unveiling pharmacogenomics insights into circular RNAs: toward precision medicine in cancer therapy. Biomolecules. 2025;15:535.
149. Long G, Ma S, Shi R, Sun Y, Hu Z, Chen K. Circular RNAs and drug resistance in genitourinary cancers: a literature review. Cancers (Basel). 2022;14:866.
