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Circular RNAs: pivotal molecular regulators and novel diagnostic and prognostic biomarkers in non-small cell lung cancer

  • Review – Cancer Research
  • Published:
Journal of Cancer Research and Clinical Oncology Aims and scope Submit manuscript

Abstract

Purpose

Circular RNAs (circRNAs), a large class of non-coding RNAs with covalently closed-loop structures, are abundant, stable, conserved, and have tissue and developmental-stage specificities. The biological functions of circRNAs are varied. Moreover, circRNAs participate in various pathological processes, especially in multiple cancers. Lung cancer is the most frequent malignant tumor worldwide. Many studies have suggested that circRNAs are pivotal in non-small cell lung cancer. This article aims to provide a retrospective review of the latest research on the functions of circRNAs in non-small cell lung cancer. In particular, we focus our discussion on the role of circRNAs in cell-cycle regulation and the epithelial–mesenchymal transition, and also discuss the known regulatory molecular mechanisms of circRNAs in non-small cell lung cancer.

Methods

We reviewed the literature on circRNAs and non-small cell lung cancer from PubMed databases. Specifically, we focused on the roles and mechanisms of circRNAs in regulating the cell cycle and the epithelial–mesenchymal transition.

Results

Dysregulation of circRNAs is closely correlated with proliferation, migration, and invasion of non-small cell lung cancer, especially in terms of modulating cell-cycle regulation and the epithelial–mesenchymal transition.

Conclusion

Taken together, circRNAs have potential as biomarkers for the diagnosis, prognosis, and treatment of non-small cell lung cancer.

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References

  • Abbas T, Dutta A (2009) p21 in cancer: intricate networks and multiple activities. Nat Rev Cancer 9:400–414

    CAS  PubMed  PubMed Central  Google Scholar 

  • Abdelmohsen K, Panda AC, Munk R, Grammatikakis I, Dudekula DB, De S, Kim J, Noh JH, Kim KM, Martindale JL, Gorospe M (2017) Identification of HuR target circular RNAs uncovers suppression of PABPN1 translation by CircPABPN1. RNA Biol 14:361–369

    PubMed  PubMed Central  Google Scholar 

  • Abe N, Matsumoto K, Nishihara M, Nakano Y, Shibata A, Maruyama H, Shuto S, Matsuda A, Yoshida M, Ito Y, Abe H (2015) Rolling circle translation of circular RNA in living human cells. Sci Rep 5:16435

    CAS  PubMed  PubMed Central  Google Scholar 

  • Ashwal-Fluss R, Meyer M, Pamudurti NR, Ivanov A, Bartok O, Hanan M, Evantal N, Memczak S, Rajewsky N, Kadener S (2014) circRNA biogenesis competes with pre-mRNA splicing. Mol Cell 56:55–66

    CAS  PubMed  Google Scholar 

  • Bahn JH, Zhang Q, Li F, Chan TM, Lin X, Kim Y, Wong DT, Xiao X (2015) The landscape of microRNA, Piwi-interacting RNA, and circular RNA in human saliva. Clin Chem 61:221–230

    CAS  PubMed  Google Scholar 

  • Bazzini AA, Johnstone TG, Christiano R, Mackowiak SD, Obermayer B, Fleming ES, Vejnar CE, Lee MT, Rajewsky N, Walther TC, Giraldez AJ (2014) Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation. EMBO J 33:981–993

    CAS  PubMed  PubMed Central  Google Scholar 

  • Beermann J, Piccoli MT, Viereck J, Thum T (2016) Non-coding RNAs in development and disease: background, mechanisms, and therapeutic approaches. Physiol Rev 96:1297–1325

    CAS  PubMed  Google Scholar 

  • Chen CY, Sarnow P (1995) Initiation of protein synthesis by the eukaryotic translational apparatus on circular RNAs. Science 268:415–417

    CAS  PubMed  Google Scholar 

  • Chen W, Zheng R, Baade PD, Zhang S, Zeng H, Bray F, Jemal A, Yu XQ, He J (2016) Cancer statistics in China, 2015. CA Cancer J Clin 66:115–132

    PubMed  Google Scholar 

  • Chen D, Ma W, Ke Z, Xie F (2018) CircRNA hsa_circ_100395 regulates miR-1228/TCF21 pathway to inhibit lung cancer progression. Cell Cycle 17:2080–2090

    CAS  PubMed  PubMed Central  Google Scholar 

  • Chin L, Hahn WC, Getz G, Meyerson M (2011) Making sense of cancer genomic data. Genes Dev 25:534–555

    CAS  PubMed  PubMed Central  Google Scholar 

  • Cho E-C, Kuo M-L, Liu X, Yang L, Hsieh Y-C, Wang J, Cheng Y, Yen Y (2014) Tumor suppressor FOXO3 regulates ribonucleotide reductase subunit RRM2B and impacts on survival of cancer patients. Oncotarget 5:4834–4844

    PubMed  PubMed Central  Google Scholar 

  • Cocquerelle C, Mascrez B, Hétuin D, Bailleul B (1993) Mis-splicing yields circular RNA molecules. FASEB J 7:155–160

    CAS  PubMed  Google Scholar 

  • Collins LG, Haines C, Perkel R, Robert EE (2007) Lung cancer: diagnosis and management. Am Fam Physician 75:56–63

    PubMed  Google Scholar 

  • Conn SJ, Pillman KA, Toubia J, Conn VM, Salmanidis M, Phillips CA, Roslan S, Schreiber AW, Gregory PA, Goodall GJ (2015) The RNA binding protein quaking regulates formation of circRNAs. Cell 160:1125–1134

    CAS  PubMed  Google Scholar 

  • Dai X, Zhang N, Cheng Y, Yang T, Chen Y, Liu Z, Wang Z, Yang C, Jiang Y (2018) RNA-binding protein trinucleotide repeat-containing 6A regulates the formation of circular RNA 0006916, with important functions in lung cancer cells. Carcinogenesis 39(8):981–992

    CAS  PubMed  Google Scholar 

  • Ding L, Yao W, Lu J, Gong J, Zhang X (2018) Upregulation of circ_001569 predicts poor prognosis and promotes cell proliferation in non-small cell lung cancer by regulating the Wnt/beta-catenin pathway. Oncol Lett 16:453–458

    PubMed  PubMed Central  Google Scholar 

  • Dong R, Zhang XO, Zhang Y, Ma XK, Chen LL, Yang L (2016) CircRNA-derived pseudogenes. Cell Res 26:747–750

    CAS  PubMed  PubMed Central  Google Scholar 

  • Du WW, Yang W, Liu E, Yang Z, Dhaliwal P, Yang BB (2016) Foxo3 circular RNA retards cell cycle progression via forming ternary complexes with p21 and CDK2. Nucleic Acids Res 44:2846–2858

    PubMed  PubMed Central  Google Scholar 

  • Du WW, Fang L, Yang W, Wu N, Awan FM, Yang Z, Yang BB (2017a) Induction of tumor apoptosis through a circular RNA enhancing Foxo3 activity. Cell Death Differ 24:357–370

    CAS  PubMed  Google Scholar 

  • Du WW, Yang W, Chen Y, Wu ZK, Foster FS, Yang Z, Li X, Yang BB (2017b) Foxo3 circular RNA promotes cardiac senescence by modulating multiple factors associated with stress and senescence responses. Eur Heart J 38:1402–1412

    CAS  PubMed  Google Scholar 

  • Ebert MS, Neilson JR, Sharp PA (2007) MicroRNA sponges: competitive inhibitors of small RNAs in mammalian cells. Nat Methods 4:721–726

    CAS  PubMed  Google Scholar 

  • Fang J, Hong H, Xue X, Zhu X, Jiang L, Qin M, Liang H, Gao L (2019) A novel circular RNA, circFAT1(e2), inhibits gastric cancer progression by targeting miR-548 g in the cytoplasm and interacting with YBX1 in the nucleus. Cancer Lett 442:222–232

    CAS  PubMed  Google Scholar 

  • Filbin ME, Kieft JS (2009) Toward a structural understanding of IRES RNA function. Curr Opin Struct Biol 19:267–276

    CAS  PubMed  PubMed Central  Google Scholar 

  • Fu L, Yao T, Chen Q, Mo X, Hu Y, Guo J (2017) Screening differential circular RNA expression profiles reveals hsa_circ_0004018 is associated with hepatocellular carcinoma. Oncotarget 8:58405

    PubMed  PubMed Central  Google Scholar 

  • Gu X, Wang G, Shen H, Fei X (2018) Hsa_circ_0033155: a potential novel biomarker for non-small cell lung cancer. Exp Ther Med 16:3220–3226

    PubMed  PubMed Central  Google Scholar 

  • Guarnerio J, Bezzi M, Jeong JC, Paffenholz SV, Berry K, Naldini MM, Lo-Coco F, Tay Y, Beck AH, Pandolfi PP (2016) Oncogenic role of fusion-circRNAs derived from cancer-associated chromosomal translocations. Cell 165:289–302

    CAS  PubMed  Google Scholar 

  • Guo T, Li J, Zhang L, Hou W, Wang R, Zhang J, Gao P (2019) Multidimensional communication of microRNAs and long non-coding RNAs in lung cancer. J Cancer Res Clin Oncol 145:31–48

    CAS  PubMed  Google Scholar 

  • Han J, Zhao G, Ma X, Dong Q, Zhang H, Wang Y, Cui J (2018) CircRNA circ-BANP-mediated miR-503/LARP1 signaling contributes to lung cancer progression. Biochem Biophys Res Commun 503:2429–2435

    CAS  PubMed  Google Scholar 

  • Hang D, Zhou J, Qin N, Zhou W, Ma H, Jin G, Hu Z, Dai J, Shen H (2018) A novel plasma circular RNA circFARSA is a potential biomarker for non-small cell lung cancer. Cancer Med 7:2783–2791

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, Kjems J (2013) Natural RNA circles function as efficient microRNA sponges. Nature 495:384–388

    CAS  PubMed  Google Scholar 

  • Hochegger H, Takeda S, Hunt T (2008) Cyclin-dependent kinases and cell-cycle transitions: does one fit all? Nat Rev Mol Cell Biol 9:910–916

    CAS  PubMed  Google Scholar 

  • Hsiao KY, Lin YC, Gupta SK, Chang N, Yen L, Sun HS, Tsai SJ (2017) Noncoding effects of circular RNA CCDC66 promote colon cancer growth and metastasis. Cancer Res 77:2339

    CAS  PubMed  PubMed Central  Google Scholar 

  • Hsu MT, Coca-Prados M (1979) Electron microscopic evidence for the circular form of RNA in the cytoplasm of eukaryotic cells. Nature 280:339–340

    CAS  PubMed  Google Scholar 

  • Ivanov A, Memczak S, Wyler E, Torti F, Porath HT, Orejuela MR, Piechotta M, Levanon EY, Landthaler M, Dieterich C, Rajewsky N (2015) Analysis of intron sequences reveals hallmarks of circular RNA biogenesis in animals. Cell Rep 10:170–177

    CAS  PubMed  Google Scholar 

  • Jeck WR, Sorrentino JA, Wang K, Slevin MK, Burd CE, Liu J, Marzluff WF, Sharpless NE (2013) Circular RNAs are abundant, conserved, and associated with ALU repeats. RNA 19:141–157

    CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang MM, Mai ZT, Wan SZ, Chi YM, Zhang X, Sun BH, Di QG (2018) Microarray profiles reveal that circular RNA hsa_circ_0007385 functions as an oncogene in non-small cell lung cancer tumorigenesis. J Cancer Res Clin Oncol 144:667–674

    CAS  PubMed  Google Scholar 

  • Karreth FA, Pandolfi PP (2013) ceRNA cross-talk in cancer: when ce-bling rivalries go awry. Cancer Discov 3:1113–1121

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kastan MB, Jiri B (2004) Cell-cycle checkpoints and cancer. Nature 432:316

    CAS  PubMed  Google Scholar 

  • Katayama R, Khan TM, Benes C, Lifshits E, Ebi H, Rivera VM, Shakespeare WC, Iafrate AJ, Engelman JA, Shaw AT (2011) Therapeutic strategies to overcome crizotinib resistance in non-small cell lung cancers harboring the fusion oncogene EML4-ALK. Proc Natl Acad Sci 108:7535–7540

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kos A, Dijkema R, Arnberg AC, van der Meide PH, Schellekens H (1986) The hepatitis delta (delta) virus possesses a circular RNA. Nature 323:558–560

    CAS  PubMed  Google Scholar 

  • Legnini I, Di Timoteo G, Rossi F, Morlando M, Briganti F, Sthandier O, Fatica A, Santini T, Andronache A, Mark W (2017) Circ-ZNF609 is a circular RNA that can be translated and functions in myogenesis. Mol Cell 66:22–37

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Zheng Q, Bao C, Li S, Guo W, Zhao J, Chen D, Gu J, He X, Huang S (2015a) Circular RNA is enriched and stable in exosomes: a promising biomarker for cancer diagnosis. Cell Res 25:981–984

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li Z, Huang C, Bao C, Chen L, Lin M, Wang X, Zhong G, Yu B, Hu W, Dai L, Zhu P, Chang Z, Wu Q, Zhao Y, Jia Y, Xu P, Liu H, Shan G (2015b) Exon–intron circular RNAs regulate transcription in the nucleus. Nat Struct Mol Biol 22:256–264

    PubMed  Google Scholar 

  • Li J, Wang J, Chen Z, Chen Y, Jin M (2018a) Hsa_circ_0079530 promotes cell proliferation and invasion in non-small cell lung cancer. Gene 665:1–5

    PubMed  Google Scholar 

  • Li S, Sun X, Miao S, Lu T, Wang Y, Liu J, Jiao W (2018b) hsa_circ_0000729, a potential prognostic biomarker in lung adenocarcinoma. Thorac Cancer 9:924–930

    CAS  PubMed  PubMed Central  Google Scholar 

  • Li S, Teng S, Xu J, Su G, Zhang Y, Zhao J, Zhang S, Wang H, Qin W, Lu ZJ, Guo Y, Zhu Q, Wang D (2019) Microarray is an efficient tool for circRNA profiling. Brief Bioinform 20(4):1420–1433

    PubMed  Google Scholar 

  • Li Y, Hu J, Li L, Cai S, Zhang H, Zhu X, Guan G, Dong X (2018d) Upregulated circular RNA circ_0016760 indicates unfavorable prognosis in NSCLC and promotes cell progression through miR-1287/GAGE1 axis. Biochem Biophys Res Commun 503:2089–2094

    CAS  PubMed  Google Scholar 

  • Liang HF, Zhang XZ, Liu BG, Jia GT, Li WL (2017) Circular RNA circ-ABCB10 promotes breast cancer proliferation and progression through sponging miR-1271. Am J Cancer Res 7:1566–1576

    CAS  PubMed  PubMed Central  Google Scholar 

  • Liu T, Song Z, Gai Y (2018a) Circular RNA circ_0001649 acts as a prognostic biomarker and inhibits NSCLC progression via sponging miR-331-3p and miR-338-5p. Biochem Biophys Res Commun 503:1503–1509

    CAS  PubMed  Google Scholar 

  • Liu W, Ma W, Yuan Y, Zhang Y, Sun S (2018b) Circular RNA hsa_circRNA_103809 promotes lung cancer progression via facilitating ZNF121-dependent MYC expression by sequestering miR-4302. Biochem Biophys Res Commun 500:846–851

    CAS  PubMed  Google Scholar 

  • Luo YH, Zhu XZ, Huang KW, Zhang Q, Fan YX, Yan PW, Wen J (2017) Emerging roles of circular RNA hsa_circ_0000064 in the proliferation and metastasis of lung cancer. Biomed Pharmacother 96:892–898

    CAS  PubMed  Google Scholar 

  • Ma X, Yang X, Bao W, Li S, Liang S, Sun Y, Zhao Y, Wang J, Zhao C (2018) Circular RNA circMAN2B2 facilitates lung cancer cell proliferation and invasion via miR-1275/FOXK1 axis. Biochem Biophys Res Commun 498:1009–1015

    CAS  PubMed  Google Scholar 

  • Mani SA, Guo W, Liao MJ, Eaton EN, Ayyanan A, Zhou AY, Brooks M, Reinhard F, Zhang CC, Shipitsin M, Campbell LL, Polyak K, Brisken C, Yang J, Weinberg RA (2008) The epithelial–mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715

    CAS  PubMed  PubMed Central  Google Scholar 

  • Massague J (2008) TGFbeta in cancer. Cell 134:215–230

    CAS  PubMed  PubMed Central  Google Scholar 

  • Massagué J (2004) G1 cell-cycle control and cancer. Nature 432:298

    PubMed  Google Scholar 

  • Memczak S, Jens M, Elefsinioti A, Torti F, Krueger J, Rybak A, Maier L, Mackowiak SD, Gregersen LH, Munschauer M, Loewer A, Ziebold U, Landthaler M, Kocks C, le Noble F, Rajewsky N (2013) Circular RNAs are a large class of animal RNAs with regulatory potency. Nature 495:333–338

    CAS  PubMed  Google Scholar 

  • Memczak S, Papavasileiou P, Peters O, Rajewsky N (2015) Identification and characterization of circular RNAs as a new class of putative biomarkers in human blood. PLoS One 10:e0141214

    PubMed  PubMed Central  Google Scholar 

  • Myatt SS, Lam EWF (2007) The emerging roles of forkhead box (Fox) proteins in cancer. Nat Rev Cancer 7:847–859

    CAS  PubMed  Google Scholar 

  • Pamudurti NR, Bartok O, Jens M, Ashwal-Fluss R, Stottmeister C, Ruhe L, Hanan M, Wyler E, Perez-Hernandez D, Ramberger E, Shenzis S, Samson M, Dittmar G, Landthaler M, Chekulaeva M, Rajewsky N, Kadener S (2017) Translation of CircRNAs. Mol Cell 66:9–21 (e7)

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pan H, Li T, Jiang Y, Pan C, Ding Y, Huang Z, Yu H, Kong D (2018) Overexpression of circular RNA ciRS-7 abrogates the tumor suppressive effect of miR-7 on gastric cancer via PTEN/PI3K/AKT signaling pathway. J Cell Biochem 119:440–446

    CAS  PubMed  Google Scholar 

  • Peinado H, Olmeda D, Cano A (2007) Snail, Zeb and bHLH factors in tumour progression: an alliance against the epithelial phenotype? Nat Rev Cancer 7:415–428

    CAS  PubMed  Google Scholar 

  • Qi Y, Zhang B, Wang J, Yao M (2018) Upregulation of circular RNA hsa_circ_0007534 predicts unfavorable prognosis for NSCLC and exerts oncogenic properties in vitro and in vivo. Gene 676:79–85

    CAS  PubMed  Google Scholar 

  • Qin M, Wei G, Sun X (2018) Circ-UBR5: an exonic circular RNA and novel small nuclear RNA involved in RNA splicing. Biochem Biophys Res Commun 503:1027–1034

    CAS  PubMed  Google Scholar 

  • Qiu M, Xia W, Chen R, Wang S, Xu Y, Ma Z, Xu W, Zhang E, Wang J, Fang T, Hu J, Dong G, Yin R, Wang J, Xu L (2018) The circular RNA circPRKCI promotes tumor growth in lung adenocarcinoma. Cancer Res 78:2839–2851

    CAS  PubMed  Google Scholar 

  • Qu S, Yang X, Li X, Wang J, Gao Y, Shang R, Sun W, Dou K, Li H (2015) Circular RNA: a new star of noncoding RNAs. Cancer Lett 365:141–148

    CAS  PubMed  Google Scholar 

  • Qu D, Yan B, Xin R, Ma T (2018) A novel circular RNA hsa_circ_0020123 exerts oncogenic properties through suppression of miR-144 in non-small cell lung cancer. Am J Cancer Res 8:1387–1402

    CAS  PubMed  PubMed Central  Google Scholar 

  • Salmena L, Poliseno L, Tay Y, Kats L, Pandolfi PP (2011) A ceRNA hypothesis: the Rosetta stone of a hidden RNA language? Cell 146:353–358

    CAS  PubMed  PubMed Central  Google Scholar 

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

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sanger HL, Klotz G, Riesner D, Gross HJ, Kleinschmidt AK (1976) Viroids are single-stranded covalently closed circular RNA molecules existing as highly base-paired rod-like structures. Proc Natl Acad Sci USA 73:3852–3856

    CAS  PubMed  PubMed Central  Google Scholar 

  • Siegel RL, Miller KD, Jemal A (2018) Cancer statistics, 2018. CA Cancer J Clin 68:7–30

    PubMed  Google Scholar 

  • Soda M, Choi YL, Enomoto M, Takada S, Yamashita Y, Ishikawa S, Fujiwara S, Watanabe H, Kurashina K, Hatanaka H, Bando M, Ohno S, Ishikawa Y, Aburatani H, Niki T, Sohara Y, Sugiyama Y, Mano H (2007) Identification of the transforming EML4–ALK fusion gene in non-small-cell lung cancer. Nature 448:561–566

    CAS  PubMed  Google Scholar 

  • Song X, Zhang N, Han P, Moon BS, Lai RK, Wang K, Lu W (2016) Circular RNA profile in gliomas revealed by identification tool UROBORUS. Nucleic Acids Res 44:e87

    PubMed  PubMed Central  Google Scholar 

  • Sumazin P, Yang X, Chiu HS, Chung WJ, Iyer A, Llobet-Navas D, Rajbhandari P, Bansal M, Guarnieri P, Silva J, Califano A (2011) An extensive microRNA-mediated network of RNA-RNA interactions regulates established oncogenic pathways in glioblastoma. Cell 147:370–381

    CAS  PubMed  PubMed Central  Google Scholar 

  • Sun C, Huang C, Li S, Yang C, Xi Y, Wang L, Zhang F, Fu Y, Li D (2016) Hsa-miR-326 targets CCND1 and inhibits non-small cell lung cancer development. Oncotarget 7:8341–8359

    PubMed  PubMed Central  Google Scholar 

  • Suzuki H, Tsukahara T (2014) A view of pre-mRNA splicing from RNase R resistant RNAs. Int J Mol Sci 15:9331–9342

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tan SM, Kirchner R, Jin J, Hofmann O, McReynolds L, Hide W, Lieberman J (2014) Sequencing of captive target transcripts identifies the network of regulated genes and functions of primate-specific miR-522. Cell Rep 8:1225–1239

    CAS  PubMed  Google Scholar 

  • Tan S, Gou Q, Pu W, Guo C, Yang Y, Wu K, Liu Y, Liu L, Wei YQ, Peng Y (2018a) Circular RNA F-circEA produced from EML4-ALK fusion gene as a novel liquid biopsy biomarker for non-small cell lung cancer. Cell Res 28:693–695

    CAS  PubMed  PubMed Central  Google Scholar 

  • Tan S, Sun D, Pu W, Gou Q, Guo C, Gong Y, Li J, Wei YQ, Liu L, Zhao Y, Peng Y (2018b) Circular RNA F-circEA-2a derived from EML4-ALK fusion gene promotes cell migration and invasion in non-small cell lung cancer. Mol Cancer 17:138

    PubMed  PubMed Central  Google Scholar 

  • Tian F, Yu CT, Ye WD, Wang Q (2017) Cinnamaldehyde induces cell apoptosis mediated by a novel circular RNA hsa_circ_0043256 in non-small cell lung cancer. Biochem Biophys Res Commun 493:1260–1266

    CAS  PubMed  Google Scholar 

  • Tian X, Zhang L, Jiao Y, Chen J, Shan Y, Yang W (2019) CircABCB10 promotes nonsmall cell lung cancer cell proliferation and migration by regulating the miR-1252/FOXR2 axis. J Cell Biochem 120:3765–3772

    CAS  PubMed  Google Scholar 

  • Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108

    PubMed  Google Scholar 

  • Van Der Vos KE, Coffer PJ (2011) The extending network of FOXO transcriptional target genes. Antioxid Redox Signal 14:579–592

    PubMed  Google Scholar 

  • Wan L, Zhang L, Fan K, Cheng ZX, Sun QC, Wang JJ (2016) Circular RNA-ITCH suppresses lung cancer proliferation via inhibiting the Wnt/beta-catenin pathway. Biomed Res Int 2016:1579490

    PubMed  PubMed Central  Google Scholar 

  • Wang J, Li H (2018) CircRNA circ_0067934 silencing inhibits the proliferation, migration and invasion of NSCLC cells and correlates with unfavorable prognosis in NSCLC. Eur Rev Med Pharmacol Sci 22:3053–3060

    CAS  PubMed  Google Scholar 

  • Wang Y, Wang Z (2015) Efficient backsplicing produces translatable circular mRNAs. RNA 21:172–179

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wang L, Liu S, Mao Y, Xu J, Yang S, Shen H, Xu W, Fan W, Wang J (2018a) CircRNF13 regulates the invasion and metastasis in lung adenocarcinoma by targeting miR-93-5p. Gene 671:170–177

    CAS  PubMed  Google Scholar 

  • Wang L, Tong X, Zhou Z, Wang S, Lei Z, Zhang T, Liu Z, Zeng Y, Li C, Zhao J, Su Z, Zhang C, Liu X, Xu G, Zhang HT (2018b) Circular RNA hsa_circ_0008305 (circPTK2) inhibits TGF-beta-induced epithelial–mesenchymal transition and metastasis by controlling TIF1gamma in non-small cell lung cancer. Mol Cancer 17(1):140

    PubMed  PubMed Central  Google Scholar 

  • Wang X, Zhu X, Zhang H, Wei S, Chen Y, Chen Y, Wang F, Fan X, Han S, Wu G (2018c) Increased circular RNA hsa_circ_0012673 acts as a sponge of miR-22 to promote lung adenocarcinoma proliferation. Biochem Biophys Res Commun 496:1069–1075

    CAS  PubMed  Google Scholar 

  • Weng W, Wei Q, Toden S, Yoshida K, Nagasaka T, Fujiwara T, Cai S, Qin H, Ma Y, Goel A (2017) Circular RNA ciRS-7—a promising prognostic biomarker and a potential therapeutic target in colorectal cancer. Clin Cancer Res 23:3918

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wood DE, George AE, David SE, Hou L, Jackman D, Kazerooni E, Klippenstein D, Rudy PL, Leard L, Ann NCL (2012) Lung cancer screening. J Natl Comp Cancer Netw 10:240–265

    CAS  Google Scholar 

  • Wu K, House L, Liu W, Cho WC (2012) Personalized targeted therapy for lung cancer. Int J Mol Sci 13:11471–11496

    CAS  PubMed  PubMed Central  Google Scholar 

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

    PubMed  Google Scholar 

  • Xu T, Wu J, Han P, Zhao Z, Song X (2017b) Circular RNA expression profiles and features in human tissues: a study using RNA-seq data. BMC Genom 18:680

    Google Scholar 

  • Yang W, Du WW, Li X, Yee AJ, Yang BB (2016) Foxo3 activity promoted by non-coding effects of circular RNA and Foxo3 pseudogene in the inhibition of tumor growth and angiogenesis. Oncogene 35:3919–3931

    CAS  PubMed  Google Scholar 

  • Yang Q, Du WW, Wu N, Yang W, Awan FM, Fang L, Ma J, Li X, Zeng Y, Yang Z, Dong J, Khorshidi A, Yang BB (2017a) A circular RNA promotes tumorigenesis by inducing c-myc nuclear translocation. Cell Death Differ 24:1609–1620

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang Y, Fan X, Mao M, Song X, Wu P, Zhang Y, Jin Y, Yang Y, Chen LL, Wang Y, Wong CC, Xiao X, Wang Z (2017b) Extensive translation of circular RNAs driven by N(6)-methyladenosine. Cell Res 27:626–641

    CAS  PubMed  PubMed Central  Google Scholar 

  • Yang L, Wang J, Fan Y, Yu K, Jiao B, Su X (2018) Hsa_circ_0046264 up-regulated BRCA2 to suppress lung cancer through targeting hsa-miR-1245. Respir Res 19:115

    PubMed  PubMed Central  Google Scholar 

  • Yao JT, Zhao SH, Liu QP, Lv MQ, Zhou DX, Liao ZJ, Nan KJ (2017) Over-expression of CircRNA_100876 in non-small cell lung cancer and its prognostic value. Pathol Res Pract 213:453–456

    CAS  PubMed  Google Scholar 

  • Yilmaz M, Christofori G (2009) EMT, the cytoskeleton, and cancer cell invasion. Cancer Metastasis Rev 28:15–33

    PubMed  Google Scholar 

  • Yu J, Xu Q, Wang Z, Yang Y, Zhang L, Ma J, Sun S, Yang F, Zhou W (2018a) Circular RNA cSMARCA5 inhibits growth and metastasis in hepatocellular carcinoma. J Hepatol 68:1214–1227

    CAS  PubMed  Google Scholar 

  • Yu W, Jiang H, Zhang H, Li J (2018b) Hsa_circ_0003998 promotes cell proliferation and invasion by targeting miR-326 in non-small cell lung cancer. Onco Targets Ther 11:5569–5577

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Zhang XO, Chen T, Xiang JF, Yin QF, Xing YH, Zhu S, Yang L, Chen LL (2013) Circular intronic long noncoding RNAs. Mol Cell 51:792–806

    CAS  PubMed  Google Scholar 

  • Zhang XO, Wang HB, Zhang Y, Lu X, Chen LL, Yang L (2014) Complementary sequence-mediated exon circularization. Cell 159:134–147

    CAS  PubMed  Google Scholar 

  • Zhang Y, Dai J, Deng H, Wan H, Liu M, Wang J, Li S, Li X, Tang H (2015) miR-1228 promotes the proliferation and metastasis of hepatoma cells through a p53 forward feedback loop. Br J Cancer 112:365–374

    CAS  PubMed  Google Scholar 

  • Zhang H, Yu C, Chen M, Li Z, Tian S, Jiang J, Sun C (2016) miR-522 contributes to cell proliferation of hepatocellular carcinoma by targeting DKK1 and SFRP2. Tumour Biol 37:11321–11329

    CAS  PubMed  Google Scholar 

  • Zhang M, Huang N, Yang X, Luo J, Yan S, Xiao F, Chen W, Gao X, Zhao K, Zhou H, Li Z, Ming L, Xie B, Zhang N (2018a) A novel protein encoded by the circular form of the SHPRH gene suppresses glioma tumorigenesis. Oncogene 37:1805–1814

    CAS  PubMed  Google Scholar 

  • Zhang S, Zeng X, Ding T, Guo L, Li Y, Ou S, Yuan H (2018b) Microarray profile of circular RNAs identifies hsa_circ_0014130 as a new circular RNA biomarker in non-small cell lung cancer. Sci Rep 8:2878

    PubMed  PubMed Central  Google Scholar 

  • Zhang X, Yang D, Wei Y (2018c) Overexpressed CDR1as functions as an oncogene to promote the tumor progression via miR-7 in non-small-cell lung cancer. Onco Targets Ther 11:3979–3987

    PubMed  PubMed Central  Google Scholar 

  • Zhang Y, Zhao H, Zhang L (2018d) Identification of the tumorsuppressive function of circular RNA FOXO3 in nonsmall cell lung cancer through sponging miR155. Mol Med Rep 17:7692–7700

    CAS  PubMed  PubMed Central  Google Scholar 

  • Zhao J, Li L, Wang Q, Han H, Zhan Q, Xu M (2017) CircRNA expression profile in early-stage lung adenocarcinoma patients. Cell Physiol Biochem 44:2138–2146

    CAS  PubMed  Google Scholar 

  • Zhao F, Han Y, Liu Z, Zhao Z, Li Z, Jia K (2018) circFADS2 regulates lung cancer cells proliferation and invasion via acting as a sponge of miR-498. Biosci Rep. https://doi.org/10.1042/BSR20180570

    Article  PubMed  PubMed Central  Google Scholar 

  • Zhou R, Chen KK, Zhang J, Xiao B, Huang Z, Ju C, Sun J, Zhang F, Lv XB, Huang G (2018) The decade of exosomal long RNA species: an emerging cancer antagonist. Mol Cancer 17:75

    PubMed  PubMed Central  Google Scholar 

  • Zhu X, Wang X, Wei S, Chen Y, Chen Y, Fan X, Han S, Wu G (2017) hsa_circ_0013958: a circular RNA and potential novel biomarker for lung adenocarcinoma. FEBS J 284:2170–2182

    CAS  PubMed  Google Scholar 

  • Zong L, Sun Q, Zhang H, Chen Z, Deng Y, Li D, Zhang L (2018) Increased expression of circRNA_102231 in lung cancer and its clinical significance. Biomed Pharmacother 102:639–644

    CAS  PubMed  Google Scholar 

  • Zou Q, Wang T, Li B, Li G, Zhang L, Wang B, Sun S (2018) Overexpression of circ-0067934 is associated with increased cellular proliferation and the prognosis of non-small cell lung cancer. Oncol Lett 16:5551–5556

    CAS  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

All of the data generated or analyzed during this study are included in this published article.

Funding

Funding was provided by the National Natural Science Foundation of China (Grant no. 81672297).

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JZ and JL contributed to the conception of the study. LZ, GM, QW, and XL contributed significantly to the analysis of data and preparation of the manuscript. CL performed data analyses and wrote the manuscript. All of the authors read and approved the final manuscript.

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Correspondence to Jie Zhang or Junyao Li.

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Li, C., Zhang, L., Meng, G. et al. Circular RNAs: pivotal molecular regulators and novel diagnostic and prognostic biomarkers in non-small cell lung cancer. J Cancer Res Clin Oncol 145, 2875–2889 (2019). https://doi.org/10.1007/s00432-019-03045-4

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  • DOI: https://doi.org/10.1007/s00432-019-03045-4

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