N6-methyladenosine modified circPAK2 promotes lymph node metastasis through focusing on IGF2BPs/VEGFA signaling in gastric most cancers


  • Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. International Most cancers Statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 international locations. CA Most cancers J Clin. 2021;71:209–49.

    PubMed 

    Google Scholar
     

  • Joshi SS, Badgwell BD. Present therapy and up to date progress in gastric most cancers. CA Most cancers J Clin. 2021;71:264–79.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li GZ, Doherty GM, Wang J. Surgical administration of gastric most cancers: a evaluate. JAMA Surg. 2022;157:446–54.

    PubMed 

    Google Scholar
     

  • Chen D, Chen G, Jiang W, Fu M, Liu W, Sui J, et al. Affiliation of the collagen signature within the tumor microenvironment with LN metastasis in early gastric most cancers. JAMA Surg. 2019;154:e185249.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Stacker SA, Williams SP, Karnezis T, Shayan R, Fox SB, Achen MG. Lymphangiogenesis and lymphatic vessel remodelling in most cancers. Nat Rev Most cancers. 2014;14:159–72.

    PubMed 

    Google Scholar
     

  • Sundar SS, Ganesan TS. Position of lymphangiogenesis in most cancers. J Clin Oncol. 2007;25:4298–307.

    PubMed 

    Google Scholar
     

  • Liu P, Ding P, Solar C, Chen S, Lowe S, Meng L, et al. Lymphangiogenesis in gastric most cancers: operate and mechanism. Eur J Med Res. 2023;28:405.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kristensen LS, Andersen MS, Stagsted LVW, Ebbesen KK, Hansen TB, Kjems J. The biogenesis, biology and characterization of round RNAs. Nat Rev Genet. 2019;20:675–91.

    PubMed 

    Google Scholar
     

  • Chen LL. The increasing regulatory mechanisms and mobile features of round RNAs. Nat Rev Mol Cell Biol. 2020;21:475–90.

    PubMed 

    Google Scholar
     

  • Liu CX, Chen LL. Round RNAs: Characterization, mobile roles, and functions. Cell. 2022;185:2016–34.

    PubMed 

    Google Scholar
     

  • Cocquerelle C, Mascrez B, Hétuin D, Bailleul B. Mis-splicing yields round RNA molecules. FASEB J. 1993;7:155–60.

    PubMed 

    Google Scholar
     

  • Chen L, Shan G. CircRNA in most cancers: elementary mechanism and scientific potential. Most cancers Lett. 2021;505:49–57.

    PubMed 

    Google Scholar
     

  • Zhang F, Jiang J, Qian H, Yan Y, Xu W. Exosomal circRNA: rising insights into most cancers development and scientific utility potential. J Hematol Oncol. 2023;16:67.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Miao S, Zhang Q. Circulating circRNA: a social butterfly in tumors. Entrance Oncol. 2023;13:1203696.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yang F, Ma Q, Huang B, Wang X, Pan X, Yu T, et al. CircNFATC3 promotes the proliferation of gastric most cancers by binding to IGF2BP3 and proscribing its ubiquitination to reinforce CCND1 mRNA stability. J Transl Med. 2023;21:402.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shen Y, Zhang N, Chai J, Wang T, Ma C, Han L, et al. CircPDIA4 induces gastric most cancers development by selling ERK1/2 activation and enhancing biogenesis of oncogenic circRNAs. Most cancers Res. 2023;83:538–52.

    PubMed 

    Google Scholar
     

  • Liu J, Niu L, Hao J, Yao Y, Yan M, Li H. circIPO7 dissociates caprin-1 from ribosomes and inhibits gastric most cancers cell proliferation by suppressing EGFR and mTOR. Oncogene. 2023;42:980–93.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang X, Li J, Bian X, Wu C, Hua J, Chang S, et al. CircURI1 interacts with hnRNPM to inhibit metastasis by modulating different splicing in gastric most cancers. Proc Natl Acad Sci USA. 2021;118:e2012881118.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Fu Y, Dominissini D, Rechavi G, He C. Gene expression regulation mediated by reversible m6A RNA methylation. Nat Rev Genet. 2014;15:293–306.

    PubMed 

    Google Scholar
     

  • Frye M, Jaffrey SR, Pan T, Rechavi G, Suzuki T. RNA modifications: what have we realized and the place are we headed? Nat Rev Genet. 2016;17:365–72.

    PubMed 

    Google Scholar
     

  • Sendinc E, Shi Y. RNA m6A methylation throughout the transcriptome. Mol Cell. 2023;83:428–41.

    PubMed 

    Google Scholar
     

  • Glažar P, Papavasileiou P, Rajewsky N. circBase: a database for round RNAs. RNA. 2014;20:1666–70.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Nassar LR, Barber GP, Benet-Pagès A, Casper J, Clawson H, Diekhans M, et al. The UCSC Genome Browser database: 2023 replace. Nucleic Acids Res. 2023;51:D1188–95.

    PubMed 

    Google Scholar
     

  • Zhong S, Feng J. CircPrimer 2.0: a software program for annotating circRNAs and predicting translation potential of circRNAs. BMC Bioinforma. 2022;23:215.


    Google Scholar
     

  • Dudekula DB, Panda AC, Grammatikakis I, De S, Abdelmohsen Okay, Gorospe M. CircInteractome: an internet instrument for exploring round RNAs and their interacting proteins and microRNAs. RNA Biol. 2016;13:34–42.

    PubMed 

    Google Scholar
     

  • Roundtree IA, Luo GZ, Zhang Z, Wang X, Zhou T, Cui Y, et al. YTHDC1 mediates nuclear export of N(6)-methyladenosine methylated mRNAs. Elife. 2017;6:e31311.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhou Y, Zeng P, Li YH, Zhang Z, Cui Q. SRAMP: prediction of mammalian N6-methyladenosine (m6A) websites primarily based on sequence-derived options. Nucleic Acids Res. 2016;44:e91.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Qi YN, Liu Z, Hong LL, Li P, Ling ZQ. Methyltransferase-like proteins in most cancers biology and potential therapeutic focusing on. J Hematol Oncol. 2023;16:89.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wei X, Huo Y, Pi J, Gao Y, Rao S, He M, et al. METTL3 preferentially enhances non-m6A translation of epigenetic elements and promotes tumourigenesis. Nat Cell Biol. 2022;24:1278–90.

    PubMed 

    Google Scholar
     

  • Xu C, Liu Okay, Ahmed H, Loppnau P, Schapira M, Min J. Structural foundation for the discriminative recognition of N6-methyladenosine RNA by the human YT521-B homology area household of proteins. J Biol Chem. 2015;290:24902–13.

    PubMed 

    Google Scholar
     

  • Huang H, Weng H, Solar W, Qin X, Shi H, Wu H, et al. Recognition of RNA N6-methyladenosine by IGF2BP proteins enhances mRNA stability and translation. Nat Cell Biol. 2018;20:285–95.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Li JH, Liu S, Zhou H, Qu LH, Yang JH. starBase v2.0: decoding miRNA-ceRNA, miRNA-ncRNA and protein-RNA interplay networks from large-scale CLIP-Seq knowledge. Nucleic Acids Res. 2014;42:D92–7.

    PubMed 

    Google Scholar
     

  • Lambert AW, Pattabiraman DR, Weinberg RA. Rising organic rules of metastasis. Cell. 2017;168:670–91.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Massagué J, Ganesh Okay. Metastasis-initiating cells and ecosystems. Most cancers Discov. 2021;11:971–94.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gerstberger S, Jiang Q, Ganesh Okay. Metastasis. Cell. 2023;186:1564–79.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zepeda-Enríquez P, Silva-Cázares MB, López-Camarillo C. Novel insights into round RNAs in metastasis in breast most cancers: an replace. Noncoding RNA. 2023;9:55.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ning J, Luo Y, Chen L, Xiao G, Tanzhu G, Zhou R. CircRNAs and lung most cancers: Perception into their roles in metastasis. Biomed Pharmacother. 2023;166:115260.

    PubMed 

    Google Scholar
     

  • Pisignano G, Michael DC, Visal TH, Pirlog R, Ladomery M, Calin GA. Going round: historical past, current, and way forward for circRNAs in most cancers. Oncogene. 2023;42:2783–800.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Dong J, Zheng Z, Zhou M, Wang Y, Chen J, Cen J, et al. EGCG-LYS fibrils-mediated CircMAP2K2 silencing decreases the proliferation and metastasis skill of gastric most cancers cells in vitro and in vivo. Adv Sci. 2023;10:e2304075.


    Google Scholar
     

  • Shen X, Kong S, Ma S, Shen L, Zheng M, Qin S, et al. Hsa_circ_0000437 promotes pathogenesis of gastric most cancers and LN metastasis. Oncogene. 2022;41:4724–35.

    PubMed 

    Google Scholar
     

  • Zang X, Jiang J, Gu J, Chen Y, Wang M, Zhang Y, et al. Round RNA EIF4G3 suppresses gastric most cancers development by inhibition of β-catenin by selling δ-catenin ubiquitin degradation and upregulating SIK1. Mol Most cancers. 2022;21:141.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Yu T, Ran L, Zhao H, Yin P, Li W, Lin J, et al. Round RNA circ-TNPO3 suppresses metastasis of GC by performing as a protein decoy for IGF2BP3 to control the expression of MYC and SNAIL. Mol Ther Nucleic Acids. 2021;26:649–64.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lu J, Wang YH, Yoon C, Huang XY, Xu Y, Xie JW, et al. Round RNA circ-RanGAP1 regulates VEGFA expression by focusing on miR-877-3p to facilitate gastric most cancers invasion and metastasis. Most cancers Lett. 2020;471:38–48.

    PubMed 

    Google Scholar
     

  • Chen Y, Yang F, Fang E, Xiao W, Mei H, Li H, et al. Round RNA circAGO2 drives most cancers development by facilitating HuR-repressed features of AGO2-miRNA complexes. Cell Dying Differ. 2019;26:1346–64.

    PubMed 

    Google Scholar
     

  • Giubelan A, Stancu MI, Honţaru SO, Mălăescu GD, Badea-Voiculescu O, Firoiu C, et al. Tumor angiogenesis in gastric most cancers. Rom J Morphol Embryol. 2023;64:311–8.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hansen TB, Jensen TI, Clausen BH, Bramsen JB, Finsen B, Damgaard CK, et al. Pure RNA circles operate as environment friendly microRNA sponges. Nature. 2013;495:384–8.

    PubMed 

    Google Scholar
     

  • Tay Y, Rinn J, Pandolfi PP. The multilayered complexity of ceRNA crosstalk and competitors. Nature. 2014;505:344–52.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Piwecka M, Glažar P, Hernandez-Miranda LR, Memczak S, Wolf SA, Rybak-Wolf A, et al. Lack of a mammalian round RNA locus causes miRNA deregulation and impacts mind operate. Science. 2017;357:eaam8526.

    PubMed 

    Google Scholar
     

  • Yan H, Zhang L, Cui X, Zheng S, Li R. Roles and mechanisms of the m6A reader YTHDC1 in organic processes and ailments. Cell Dying Discov. 2022;8:237.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhou H, Solar Q, Feng M, Gao Z, Jia S, Cao L, et al. Regulatory mechanisms and therapeutic implications of insulin-like progress issue 2 mRNA-binding proteins, the rising essential m6A regulators of tumors. Theranostics. 2023;13:4247–65.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu Y, Yang D, Liu T, Chen J, Yu J, Yi P. N6-methyladenosine-mediated gene regulation and therapeutic implications. Tendencies Mol Med. 2023 Jun;29:454–67.

    PubMed 

    Google Scholar
     

  • Fan HN, Chen ZY, Chen XY, Chen M, Yi YC, Zhu JS, et al. METTL14-mediatedm6A modification of circORC5 suppresses gastric most cancers development by regulating miR-30c-2-3p/AKT1S1 axis. Mol Most cancers. 2022;21:51.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang JY, Du Y, Gong LP, Shao YT, Pan LJ, Feng ZY, et al. ebv-circRPMS1 promotes the development of EBV-associated gastric carcinoma through Sam68-dependent activation of METTL3. Most cancers Lett. 2022;535:215646.

    PubMed 

    Google Scholar
     

  • Wu X, Fang Y, Gu Y, Shen H, Xu Y, Xu T, et al. Fats mass and obesity-associated protein (FTO) mediated m6A modification of circFAM192A promoted gastric most cancers proliferation by suppressing SLC7A5 decay. Mol Biomed. 2024;5:11.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen RX, Chen X, Xia LP, Zhang JX, Pan ZZ, Ma XD, et al. N6-methyladenosine modification of circNSUN2 facilitates cytoplasmic export and stabilizes HMGA2 to advertise colorectal liver metastasis. Nat Commun. 2019;10:4695.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Di Timoteo G, Dattilo D, Centrón-Broco A, Colantoni A, Guarnacci M, Rossi F, et al. Modulation of circRNA Metabolism by m6A Modification. Cell Rep. 2020;31:107641.

    PubMed 

    Google Scholar
     

  • Korn SM, Ulshöfer CJ, Schneider T, Schlundt A. Constructions and goal RNA preferences of the RNA-binding protein household of IGF2BPs: an outline. Construction. 2021;29:787–803.

    PubMed 

    Google Scholar
     

  • Bell JL, Wächter Okay, Mühleck B, Pazaitis N, Köhn M, Lederer M, et al. Insulin-like progress issue 2 mRNA-binding proteins (IGF2BPs): post-transcriptional drivers of most cancers development? Cell Mol Life Sci. 2013;70:2657–75.

    PubMed 

    Google Scholar
     

  • Huang X, Zhang H, Guo X, Zhu Z, Cai H, Kong X. Insulin-like progress issue 2 mRNA-binding protein 1 (IGF2BP1) in most cancers. J Hematol Oncol. 2018;11:88.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Wang J, Chen L, Qiang P. The position of IGF2BP2, an m6A reader gene, in human metabolic ailments and cancers. Most cancers Cell Int. 2021;21:99.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Lederer M, Bley N, Schleifer C, Hüttelmaier S. The position of the oncofetal IGF2 mRNA-binding protein 3 (IGF2BP3) in most cancers. Semin Most cancers Biol. 2014;29:3–12.

    PubMed 

    Google Scholar
     

  • Zhang L, Zhang Y, Li X, Gao H, Chen X, Li P. CircRNA-miRNA-VEGFA: an necessary pathway to control most cancers pathogenesis. Entrance Pharmacol. 2023;14:1049742.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Du Y, Zhang JY, Gong LP, Feng ZY, Wang D, Pan YH, et al. Hypoxia-induced ebv-circLMP2A promotes angiogenesis in EBV-associated gastric carcinoma by the KHSRP/VHL/HIF1α/VEGFA pathway. Most cancers Lett. 2022;526:259–72.

    PubMed 

    Google Scholar
     

  • Xie M, Yu T, Jing X, Ma L, Fan Y, Yang F, et al. Exosomal circSHKBP1 promotes gastric most cancers development through regulating the miR-582-3p/HUR/VEGF axis and suppressing HSP90 degradation. Mol Most cancers. 2020;19:112.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Matsumoto Okay, Ema M. Roles of VEGF-A signalling in improvement, regeneration, and tumours. J Biochem. 2014;156:1–10.

    PubMed 

    Google Scholar
     

  • Dou R, Han L, Yang C, Fang Y, Zheng J, Liang C, et al. Upregulation of LINC00501 by H3K27 acetylation facilitates gastric most cancers metastasis by activating epithelial-mesenchymal transition and angiogenesis. Clin Transl Med. 2023;13:e1432.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Langmead B, Salzberg SL. Quick gapped-read alignment with Bowtie 2. Nat Strategies. 2012;9:357–9.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim D, Langmead B, Salzberg SL. HISAT: a quick spliced aligner with low reminiscence necessities. Nat Strategies. 2015;12:357–60.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kim D, Salzberg SL. TopHat-Fusion: an algorithm for discovery of novel fusion transcripts. Genome Biol. 2011;12:R72.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang XO, Dong R, Zhang Y, Zhang JL, Luo Z, Zhang J, et al. Numerous different back-splicing and different splicing panorama of round RNAs. Genome Res. 2016;26:1277–87.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang XO, Wang HB, Zhang Y, Lu X, Chen LL, Yang L. Complementary sequence-mediated exon circularization. Cell. 2014;159:134–47.

    PubMed 

    Google Scholar
     

  • Gao Y, Wang J, Zhao F. CIRI: an environment friendly and unbiased algorithm for de novo round RNA identification. Genome Biol. 2015;16:4.

    PubMed 
    PubMed Central 

    Google Scholar
     

  • Hot Topics

    Related Articles