Skip to main content
SpringerLink
Log in

SNORD17-mediated KAT6B mRNA 2’-O-methylation regulates vasculogenic mimicry in glioblastoma cells

  • Research
  • Published:
Cell Biology and Toxicology Aims and scope Submit manuscript

Abstract

Glioblastoma (GBM) is a primary tumor in the intracranial compartment. Vasculogenic mimicry (VM) is a process in which a pipeline of tumor cells that provide blood support to carcinogenic cells is formed, and studying VM could provide a new strategy for clinical targeted treatment of GBM. In the present study, we found that SNORD17 and ZNF384 were significantly upregulated and promoted VM in GBM, whereas KAT6B was downregulated and inhibited VM in GBM. RTL-P assays were performed to verify the 2’-O-methylation of KAT6B by SNORD17; IP assays were used to detect the acetylation of ZNF384 by KAT6B. In addition, the binding of ZNF384 to the promoter regions of VEGFR2 and VE-cadherin promoted transcription, as validated by chromatin immunoprecipitation and luciferase reporter assays. And finally, knockdown of SNORD17 and ZNF384 combined with KAT6B overexpression effectively reduced the xenograft tumor size, prolonged the survival time of nude mice and reduced the number of VM channels. This study reveals a novel mechanism of the SNORD17/KAT6B/ZNF384 axis in modulating VM development in GBM that may provide a new goal for the comprehensive treatment of GBM.

Graphical Abstract

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8

Similar content being viewed by others

Data availability

Data are available on reasonable request.

References

  • Ayadi L, Galvanin A, Pichot F, Marchand V, Motorin Y. RNA ribose methylation (2'-O-methylation): Occurrence, biosynthesis and biological functions. Biochim Biophys Acta Gene Regul Mech. 2019;1862:253–69.

    Article  CAS  PubMed  Google Scholar 

  • Camorani S, Crescenzi E, Gramanzini M, Fedele M, Zannetti A, Cerchia L. Aptamer-mediated impairment of EGFR-integrin alphavbeta3 complex inhibits vasculogenic mimicry and growth of triple-negative breast cancers. Sci Rep. 2017;7:46659.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen YS, Chen ZP. Vasculogenic mimicry: a novel target for glioma therapy. Chin J Cancer. 2014;33:74–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen J, Chen S, Zhuo L, Zhu Y, Zheng H. Regulation of cancer stem cell properties, angiogenesis, and vasculogenic mimicry by miR-450a-5p/SOX2 axis in colorectal cancer. Cell Death Dis. 2020;11:173.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Chen S, Li X, Wang H, Chen G, Zhou Y. Anti-VEGFR2 monoclonal antibody(MSB0254) inhibits angiogenesis and tumor growth by blocking the signaling pathway mediated by VEGFR2 in glioblastoma. Biochem Biophys Res Commun. 2022;604:158–64.

    Article  CAS  PubMed  Google Scholar 

  • Comito G, Calvani M, Giannoni E, Bianchini F, Calorini L, Torre E, Migliore C, Giordano S, Chiarugi P. HIF-1alpha stabilization by mitochondrial ROS promotes Met-dependent invasive growth and vasculogenic mimicry in melanoma cells. Free Radic Biol Med. 2011;51:893–904.

    Article  CAS  PubMed  Google Scholar 

  • Dai Q, Moshitch-Moshkovitz S, Han D, Kol N, Amariglio N, Rechavi G, Dominissini D, He C. Nm-seq maps 2'-O-methylation sites in human mRNA with base precision. Nat Methods. 2017;14:695–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Deng T, Gong Y, Liao X, Wang X, Zhou X, Zhu G, Mo L. Integrative Analysis of a Novel Eleven-Small Nucleolar RNA Prognostic Signature in Patients With Lower Grade Glioma. Front Oncol. 2021;11:650828.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ding H, Shi Y, Liu X, Qiu A. MicroRNA-4513 Promotes Gastric Cancer Cell Proliferation and Epithelial-Mesenchymal Transition Through Targeting KAT6B. Hum Gene Ther Clin Dev. 2019;30:142–8.

    Article  CAS  PubMed  Google Scholar 

  • Dong W, Liu X, Yang C, Wang D, Xue Y, Ruan X, Zhang M, Song J, Cai H, Zheng J, Liu Y. Glioma glycolipid metabolism: MSI2-SNORD12B-FIP1L1-ZBTB4 feedback loop as a potential treatment target. Clin Transl Med. 2021;11:e411.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Downey M. Non-histone protein acetylation by the evolutionarily conserved GCN5 and PCAF acetyltransferases. Biochim Biophys Acta Gene Regul Mech. 2021;1864:194608.

    Article  CAS  PubMed  Google Scholar 

  • Elliott BA, Ho HT, Ranganathan SV, Vangaveti S, Ilkayeva O, Abou Assi H, Choi AK, Agris PF, Holley CL. Modification of messenger RNA by 2'-O-methylation regulates gene expression in vivo. Nat Commun. 2019;10:3401.

    Article  PubMed  PubMed Central  Google Scholar 

  • Falaleeva M, Pages A, Matuszek Z, Hidmi S, Agranat-Tamir L, Korotkov K, Nevo Y, Eyras E, Sperling R, Stamm S. Dual function of C/D box small nucleolar RNAs in rRNA modification and alternative pre-mRNA splicing. Proc Natl Acad Sci U S A. 2016;113:E1625–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Fang JH, Zheng ZY, Liu JY, Xie C, Zhang ZJ, Zhuang SM. Regulatory Role of the MicroRNA-29b-IL-6 Signaling in the Formation of Vascular Mimicry. Mol Ther Nucleic Acids. 2017;8:90–100.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gao YY, Ling ZY, Zhu YR, Shi C, Wang Y, Zhang XY, Zhang ZQ, Jiang Q, Chen MB, Yang S, Cao C. The histone acetyltransferase HBO1 functions as a novel oncogenic gene in osteosarcoma. Theranostics. 2021;11:4599–615.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gronroos E, Hellman U, Heldin CH, Ericsson J. Control of Smad7 stability by competition between acetylation and ubiquitination. Mol Cell. 2002;10:483–93.

    Article  CAS  PubMed  Google Scholar 

  • Guy MP, Podyma BM, Preston MA, Shaheen HH, Krivos KL, Limbach PA, Hopper AK, Phizicky EM. Yeast Trm7 interacts with distinct proteins for critical modifications of the tRNAPhe anticodon loop. RNA. 2012;18:1921–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • He L, Fan X, Li Y, Chen M, Cui B, Chen G, Dai Y, Zhou D, Hu X, Lin H. Overexpression of zinc finger protein 384 (ZNF 384), a poor prognostic predictor, promotes cell growth by upregulating the expression of Cyclin D1 in Hepatocellular carcinoma. Cell Death Dis. 2019;10:444.

    Article  PubMed  PubMed Central  Google Scholar 

  • Herrington CS, Poulsom R, Coates PJ. Recent Advances in Pathology: the 2020 Annual Review Issue of The Journal of Pathology. J Pathol. 2020;250:475–9.

    Article  PubMed  Google Scholar 

  • Huang L, Liang XZ, Deng Y, Liang YB, Zhu X, Liang XY, Luo DZ, Chen G, Fang YY, Lan HH, Zeng JH. Prognostic value of small nucleolar RNAs (snoRNAs) for colon adenocarcinoma based on RNA sequencing data. Pathol Res Pract. 2020;216:152937.

    Article  CAS  PubMed  Google Scholar 

  • Jiang W, Wang S, Xiao M, Lin Y, Zhou L, Lei Q, Xiong Y, Guan KL, Zhao S. Acetylation regulates gluconeogenesis by promoting PEPCK1 degradation via recruiting the UBR5 ubiquitin ligase. Mol Cell. 2011;43:33–44.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jiang J, Wang HJ, Mou XZ, Zhang H, Chen Y, Hu ZM. Low Expression of KAT6B May Affect Prognosis in Hepatocellular Carcinoma. Technol Cancer Res Treat. 2021;20:15330338211033063.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jockel S, Nees G, Sommer R, Zhao Y, Cherkasov D, Hori H, Ehm G, Schnare M, Nain M, Kaufmann A, Bauer S. The 2'-O-methylation status of a single guanosine controls transfer RNA-mediated Toll-like receptor 7 activation or inhibition. J Exp Med. 2012;209:235–41.

    Article  PubMed  PubMed Central  Google Scholar 

  • Kotelawala L, Grayhack EJ, Phizicky EM. Identification of yeast tRNA Um(44) 2'-O-methyltransferase (Trm44) and demonstration of a Trm44 role in sustaining levels of specific tRNA(Ser) species. RNA. 2008;14:158–69.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Li Y, Wu Z, Yuan J, Sun L, Lin L, Huang N, Bin J, Liao Y, Liao W. Long non-coding RNA MALAT1 promotes gastric cancer tumorigenicity and metastasis by regulating vasculogenic mimicry and angiogenesis. Cancer Lett. 2017;395:31–44.

    Article  CAS  PubMed  Google Scholar 

  • Li X, Xue Y, Liu X, Zheng J, Shen S, Yang C, Chen J, Li Z, Liu L, Ma J, et al. ZRANB2/SNHG20/FOXK1 Axis regulates Vasculogenic mimicry formation in glioma. J Exp Clin Cancer Res. 2019;38:68.

    Article  PubMed  PubMed Central  Google Scholar 

  • Li H, Wang D, Yi B, Cai H, Wang Y, Lou X, Xi Z, Li Z. SUMOylation of IGF2BP2 promotes vasculogenic mimicry of glioma via regulating OIP5-AS1/miR-495-3p axis. Int J Biol Sci. 2021;17:2912–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Liang J, Li G, Liao J, Huang Z, Wen J, Wang Y, Chen Z, Cai G, Xu W, Ding Z, et al. Non-coding small nucleolar RNA SNORD17 promotes the progression of hepatocellular carcinoma through a positive feedback loop upon p53 inactivation. Cell Death Differ. 2022;29:988–1003.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Luo Q, Wang J, Zhao W, Peng Z, Liu X, Li B, Zhang H, Shan B, Zhang C, Duan C. Vasculogenic mimicry in carcinogenesis and clinical applications. J Hematol Oncol. 2020;13:19.

    Article  PubMed  PubMed Central  Google Scholar 

  • Maniotis AJ, Folberg R, Hess A, Seftor EA, Gardner LM, Pe'er J, Trent JM, Meltzer PS, Hendrix MJ. Vascular channel formation by human melanoma cells in vivo and in vitro: vasculogenic mimicry. Am J Pathol. 1999;155:739–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nachmani D, Bothmer AH, Grisendi S, Mele A, Bothmer D, Lee JD, Monteleone E, Cheng K, Zhang Y, Bester AC, et al. Germline NPM1 mutations lead to altered rRNA 2'-O-methylation and cause dyskeratosis congenita. Nat Genet. 2019;51:1518–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Nakamoto T, Yamagata T, Sakai R, Ogawa S, Honda H, Ueno H, Hirano N, Yazaki Y, Hirai H. CIZ, a zinc finger protein that interacts with p130(cas) and activates the expression of matrix metalloproteinases. Mol Cell Biol. 2000;20:1649–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Narita T, Weinert BT, Choudhary C. Functions and mechanisms of non-histone protein acetylation. Nat Rev Mol Cell Biol. 2019;20:156–74.

    Article  CAS  PubMed  Google Scholar 

  • Nisar MA, Zheng Q, Saleem MZ, Ahmmed B, Ramzan MN, Ud Din SR, Tahir N, Liu S, Yan Q. IL-1beta Promotes Vasculogenic Mimicry of Breast Cancer Cells Through p38/MAPK and PI3K/Akt Signaling Pathways. Front Oncol. 2021;11:618839.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peng Z, Wang J, Shan B, Li B, Peng W, Dong Y, Shi W, Zhao W, He D, Duan M, et al. The long noncoding RNA LINC00312 induces lung adenocarcinoma migration and vasculogenic mimicry through directly binding YBX1. Mol Cancer. 2018;17:167.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Prado MCM, Macedo SAL, Guiraldelli GG, de Faria Lainetti P, Leis-Filho AF, Kobayashi PE, Laufer-Amorim R, Fonseca-Alves CE. Investigation of the Prognostic Significance of Vasculogenic Mimicry and Its Inhibition by Sorafenib in Canine Mammary Gland Tumors. Front Oncol. 2019;9:1445.

    Article  PubMed  PubMed Central  Google Scholar 

  • Rae K, Funk H, Guy A, Guy M. Study of Trm7 Interactions With Binding Partners Trm732 and Trm734 for 2'-O-Methylation of the tRNA Anticodon Loop in Yeast. FASEB J. 2022;36(Suppl):1.

    Google Scholar 

  • Shubina MY, Musinova YR, Sheval EV. Nucleolar Methyltransferase Fibrillarin: Evolution of Structure and Functions. Biochemistry. 2016;81:941–50.

    CAS  PubMed  Google Scholar 

  • Simo-Riudalbas L, Perez-Salvia M, Setien F, Villanueva A, Moutinho C, Martinez-Cardus A, Moran S, Berdasco M, Gomez A, Vidal E, et al. KAT6B Is a Tumor Suppressor Histone H3 Lysine 23 Acetyltransferase Undergoing Genomic Loss in Small Cell Lung Cancer. Cancer Res. 2015;75:3936–45.

    Article  CAS  PubMed  Google Scholar 

  • Soda Y, Myskiw C, Rommel A, Verma IM. Mechanisms of neovascularization and resistance to anti-angiogenic therapies in glioblastoma multiforme. J Mol Med. 2013;91:439–48.

    Article  CAS  PubMed  Google Scholar 

  • Stepanov GA, Filippova JA, Komissarov AB, Kuligina EV, Richter VA, Semenov DV. Regulatory role of small nucleolar RNAs in human diseases. Biomed Res Int. 2015;2015:206849.

    Article  PubMed  PubMed Central  Google Scholar 

  • Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, Belanger K, Brandes AA, Marosi C, Bogdahn U, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352:987–96.

    Article  CAS  PubMed  Google Scholar 

  • Wang F, Chan CH, Chen K, Guan X, Lin HK, Tong Q. Deacetylation of FOXO3 by SIRT1 or SIRT2 leads to Skp2-mediated FOXO3 ubiquitination and degradation. Oncogene. 2012;31:1546–57.

    Article  CAS  PubMed  Google Scholar 

  • Wang W, Lin P, Sun B, Zhang S, Cai W, Han C, Li L, Lu H, Zhao X. Epithelial-mesenchymal transition regulated by EphA2 contributes to vasculogenic mimicry formation of head and neck squamous cell carcinoma. Biomed Res Int. 2014;2014:803914.

    PubMed  PubMed Central  Google Scholar 

  • Wang D, Ruan X, Liu X, Xue Y, Shao L, Yang C, Zhu L, Yang Y, Li Z, Yu B, et al. SUMOylation of PUM2 promotes the vasculogenic mimicry of glioma cells via regulating CEBPD. Clin Transl Med. 2020;10:e168.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wick W, Osswald M, Wick A, Winkler F. Treatment of glioblastoma in adults. Ther Adv Neurol Disord. 2018;11:1756286418790452.

    Article  PubMed  PubMed Central  Google Scholar 

  • Wu S, Yu L, Wang D, Zhou L, Cheng Z, Chai D, Ma L, Tao Y. Aberrant expression of CD133 in non-small cell lung cancer and its relationship to vasculogenic mimicry. BMC Cancer. 2012;12:535.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Wu H, Qin W, Lu S, Wang X, Zhang J, Sun T, Hu X, Li Y, Chen Q, Wang Y, et al. Long noncoding RNA ZFAS1 promoting small nucleolar RNA-mediated 2'-O-methylation via NOP58 recruitment in colorectal cancer. Mol Cancer. 2020;19:95.

    Article  PubMed  PubMed Central  Google Scholar 

  • Xu Y, Li Q, Li XY, Yang QY, Xu WW, Liu GL. Short-term anti-vascular endothelial growth factor treatment elicits vasculogenic mimicry formation of tumors to accelerate metastasis. J Exp Clin Cancer Res. 2012;31:16.

    Article  PubMed  PubMed Central  Google Scholar 

  • Yan Z, Zhou Y, Yang Y, Zeng C, Li P, Tian H, Tang X, Zhang G. Zinc finger protein 384 enhances colorectal cancer metastasis by upregulating MMP2. Oncol Rep. 2022;47:1–15.

  • Yu S, Ruan X, Liu X, Zhang F, Wang D, Liu Y, Yang C, Shao L, Liu Q, Zhu L, et al. HNRNPD interacts with ZHX2 regulating the vasculogenic mimicry formation of glioma cells via linc00707/miR-651-3p/SP2 axis. Cell Death Dis. 2021;12:153.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zhu Y, Liu X, Zhao P, Zhao H, Gao W, Wang L. Celastrol Suppresses Glioma Vasculogenic Mimicry Formation and Angiogenesis by Blocking the PI3K/Akt/mTOR Signaling Pathway. Front Pharmacol. 2020;11:25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Zong S, Tang Y, Li W, Han S, Shi Q, Ruan X, Hou F. A Chinese Herbal Formula Suppresses Colorectal Cancer Migration and Vasculogenic Mimicry Through ROS/HIF-1alpha/MMP2 Pathway in Hypoxic Microenvironment. Front Pharmacol. 2020;11:705.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgments

Not applicable

Funding

This work is supported by grants from the Natural Science Foundation of China (82173071, 82272846); the Project of Key Laboratory of Neuro-oncology in Liaoning Province (112-2400017005); and the 2020 Shenyang Research and Development Special Project in Public Health (No. 20-205-4-013).

Author information

Authors and Affiliations

  1. Department of Neurobiology, School of Life Sciences, China Medical University, Shenyang, 110122, China

    Jingyi Cui, Xuelei Ruan, Mengyang Zhang, Ping Wang, Libo Liu & Yixue Xue

  2. Key Laboratory of Neuro-oncology in Liaoning Province, Shenyang, 110004, China

    Jingyi Cui, Xiaobai Liu, Weiwei Dong, Yunhui Liu, Xuelei Ruan, Mengyang Zhang, Ping Wang, Libo Liu & Yixue Xue

  3. Department of Neurosurgery, Shengjing Hospital of China Medical University, Shenyang, 110004, China

    Xiaobai Liu, Weiwei Dong & Yunhui Liu

Authors
  1. Jingyi Cui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Xiaobai Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Weiwei Dong
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Yunhui Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Xuelei Ruan
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mengyang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Ping Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Libo Liu
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Yixue Xue
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

Y.X.X and Y.H.L designed the project. J.Y.C. contributed to performing most of the experiments. J.Y.C. and X.B.L., and W.W.D. wrote the manuscript. X.L.R. and M.Y.Z. performed the statistical analysis. M.Y.Z., P.W. and L.B.L. were mainly responsible for proofreading. All authors approved the final paper.

Corresponding author

Correspondence to Yixue Xue.

Ethics declarations

Competing interests

The authors declare no competing interests.

Ethics approval

The study of human tissues was approved by the ethics committee of Shengjing Hospital affiliated with China Medical University with the informed consent of the patients and was conducted in accordance with the Declaration of Helsinki and national laws. For animal studies, the experimental procedures according to the China Medical University guidelines were submitted to and approved by the ethics committee of China Medical University.

Consent for publication

Not applicable.

Additional information

Publisher’s note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary information

ESM 1

(DOCX 3.87 MB)

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Cui, J., Liu, X., Dong, W. et al. SNORD17-mediated KAT6B mRNA 2’-O-methylation regulates vasculogenic mimicry in glioblastoma cells. Cell Biol Toxicol 39, 2841–2860 (2023). https://doi.org/10.1007/s10565-023-09805-w

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10565-023-09805-w

Keywords

Search

Navigation