Skip to main content
Log in

LncRNA SNHG25 Promotes Glioma Progression Through Activating MAPK Signaling

  • Published:
Molecular Neurobiology Aims and scope Submit manuscript

Abstract

Numerous studies indicated that long non-coding RNAs (lncRNAs) play critical roles in glioma initiation and progression. SNHG25 is a newly identified lncRNA. And the functional role and molecular mechanism of SNHG25 in glioma cells have not been investigated. In this study, we found that SNHG25 was upregulated in glioma cells and tissues. CCK-8, EDU, and colony formation assays demonstrated that SNHG25 knockdown markedly inhibited glioma cell proliferation. In vivo studies showed that SNHG25 knockdown significantly inhibited tumor growth. Further studies indicated that SNHG25 positively regulated MAP2K2 through sponging miR-579-5p. High expression of SNHG25 activated MAPK signaling through MAP2K2. These data suggest that SNHG25 is a potential target and biomarker for glioma.

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

Access this article

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

Instant access to the full article PDF.

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

Similar content being viewed by others

Data Availability

The datasets used or analyzed during the study are available from the corresponding author on reasonable request.

References

  1. Nicholson JG, Fine HA (2021) Diffuse glioma heterogeneity and its therapeutic implications. Cancer Discov 11(3):575–590. https://doi.org/10.1158/2159-8290.CD-20-1474

    Article  CAS  PubMed  Google Scholar 

  2. Gao X, Xia X, Li F, Zhang M, Zhou H, Wu X, Zhong J, Zhao Z et al (2021) Circular RNA-encoded oncogenic E-cadherin variant promotes glioblastoma tumorigenicity through activation of EGFR-STAT3 signalling. Nat Cell Biol 23(3):278–291. https://doi.org/10.1038/s41556-021-00639-4

    Article  CAS  PubMed  Google Scholar 

  3. Wang LB, Karpova A, Gritsenko MA, Kyle JE, Cao S, Li Y, Rykunov D, Colaprico A et al (2021) Proteogenomic and metabolomic characterization of human glioblastoma. Cancer Cell 39(4):509–528. https://doi.org/10.1016/j.ccell.2021.01.006 (e520)

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144(5):646–674. https://doi.org/10.1016/j.cell.2011.02.013

    Article  CAS  PubMed  Google Scholar 

  5. Li X, Qian X, Wang B, Xia Y, Zheng Y, Du L, Xu D, Xing D et al (2020) Programmable base editing of mutated TERT promoter inhibits brain tumour growth. Nat Cell Biol 22(3):282–288. https://doi.org/10.1038/s41556-020-0471-6

    Article  CAS  PubMed  Google Scholar 

  6. Kofuji S, Hirayama A, Eberhardt AO, Kawaguchi R, Sugiura Y, Sampetrean O, Ikeda Y, Warren M et al (2019) IMP dehydrogenase-2 drives aberrant nucleolar activity and promotes tumorigenesis in glioblastoma. Nat Cell Biol 21(8):1003–1014. https://doi.org/10.1038/s41556-019-0363-9

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Duman C, Yaqubi K, Hoffmann A, Acikgoz AA, Korshunov A, Bendszus M, Herold-Mende C, Liu HK, Alfonso J (2019) Acyl-CoA-binding protein drives glioblastoma tumorigenesis by sustaining fatty acid oxidation. Cell Metab 30(2):274–289. https://doi.org/10.1016/j.cmet.2019.04.004 (e275)

    Article  CAS  PubMed  Google Scholar 

  8. Winkle M, El-Daly SM, Fabbri M, Calin GA (2021) Noncoding RNA therapeutics - challenges and potential solutions. Nat Rev Drug Discov. https://doi.org/10.1038/s41573-021-00219-z

    Article  PubMed  PubMed Central  Google Scholar 

  9. Zhao D, Chen H, Wang B (2021) Assessing the regulatory functions of LncRNA SNHG11 in gastric cancer cell proliferation and migration. Front Cell Dev Biol 9:620476. https://doi.org/10.3389/fcell.2021.620476

    Article  PubMed  PubMed Central  Google Scholar 

  10. Wu Q, Ma J, Wei J, Meng W, Wang Y, Shi M (2021) lncRNA SNHG11 promotes gastric cancer progression by activating the Wnt/beta-catenin pathway and oncogenic autophagy. Mol Ther 29(3):1258–1278. https://doi.org/10.1016/j.ymthe.2020.10.011

    Article  CAS  PubMed  Google Scholar 

  11. Chen L, Miao X, Si C, Qin A, Zhang Y, Chu C, Li Z, Wang T et al (2021) Long non-coding RNA SENP3-EIF4A1 Functions as a Sponge of miR-195-5p to drive triple-negative breast cancer progress by overexpressing CCNE1. Front Cell Dev Biol 9:647527. https://doi.org/10.3389/fcell.2021.647527

    Article  PubMed  PubMed Central  Google Scholar 

  12. Sheng J, He X, Yu W, Chen Y, Long Y, Wang K, Zhu S, Liu Q (2021) p53-targeted lncRNA ST7-AS1 acts as a tumour suppressor by interacting with PTBP1 to suppress the Wnt/beta-catenin signalling pathway in glioma. Cancer Lett 503:54–68. https://doi.org/10.1016/j.canlet.2020.12.039

    Article  CAS  PubMed  Google Scholar 

  13. Cai H, Yu Y, Ni X, Li C, Hu Y, Wang J, Chen F, Xi S et al (2020) LncRNA LINC00998 inhibits the malignant glioma phenotype via the CBX3-mediated c-Met/Akt/mTOR axis. Cell Death Dis 11(12):1032. https://doi.org/10.1038/s41419-020-03247-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Liu Y, Xu B, Liu M, Qiao H, Zhang S, Qiu J, Ying X (2021) Long non-coding RNA SNHG25 promotes epithelial ovarian cancer progression by up-regulating COMP. J Cancer 12(6):1660–1668. https://doi.org/10.7150/jca.47344

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Liu SJ, Dang HX, Lim DA, Feng FY, Maher CA (2021) Long noncoding RNAs in cancer metastasis. Nat Rev Cancer. https://doi.org/10.1038/s41568-021-00353-1

    Article  PubMed  PubMed Central  Google Scholar 

  16. Chen Y, Zitello E, Guo R, Deng Y (2021) The function of LncRNAs and their role in the prediction, diagnosis, and prognosis of lung cancer. Clin Transl Med 11(4):e367. https://doi.org/10.1002/ctm2.367

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Kim SH, Lim KH, Yang S, Joo JY (2021) Long non-coding RNAs in brain tumors: roles and potential as therapeutic targets. J Hematol Oncol 14(1):77. https://doi.org/10.1186/s13045-021-01088-0

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Ji J, Xu R, Ding K, Bao G, Zhang X, Huang B, Wang X, Martinez A et al (2019) Long noncoding RNA SChLAP1 forms a growth-promoting complex with HNRNPL in human glioblastoma through stabilization of ACTN4 and activation of NF-kappaB signaling. Clin Cancer Res 25(22):6868–6881. https://doi.org/10.1158/1078-0432.CCR-19-0747

    Article  CAS  PubMed  Google Scholar 

  19. Qiu G, Tong W, Jiang C, Xie Q, Zou J, Luo C, Zhao J, Zhang L et al (2020) Long noncoding RNA WT1-AS inhibit cell malignancy via miR-494-3p in glioma. Technol Cancer Res Treat 19:1533033820919759. https://doi.org/10.1177/1533033820919759

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Xia P, Li Q, Wu G, Huang Y (2021) An immune-related lncRNA signature to predict survival in glioma patients. Cell Mol Neurobiol 41(2):365–375. https://doi.org/10.1007/s10571-020-00857-8

    Article  CAS  PubMed  Google Scholar 

  21. Lu C, Wei Y, Wang X, Zhang Z, Yin J, Li W, Chen L, Lyu X et al (2020) DNA-methylation-mediated activating of lncRNA SNHG12 promotes temozolomide resistance in glioblastoma. Mol Cancer 19(1):28. https://doi.org/10.1186/s12943-020-1137-5

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Chen Q, Cai J, Wang Q, Wang Y, Liu M, Yang J, Zhou J, Kang C et al (2018) Long noncoding RNA NEAT1, regulated by the EGFR pathway, contributes to glioblastoma progression through the WNT/beta-catenin pathway by scaffolding EZH2. Clin Cancer Res 24(3):684–695. https://doi.org/10.1158/1078-0432.CCR-17-0605

    Article  CAS  PubMed  Google Scholar 

  23. Buccarelli M, Lulli V, Giuliani A, Signore M, Martini M, D’Alessandris QG, Giannetti S, Novelli A et al (2020) Deregulated expression of the imprinted DLK1-DIO3 region in glioblastoma stemlike cells: tumor suppressor role of lncRNA MEG3. Neuro Oncol 22(12):1771–1784. https://doi.org/10.1093/neuonc/noaa127

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Liao Y, Shen L, Zhao H, Liu Q, Fu J, Guo Y, Peng R, Cheng L (2017) LncRNA CASC2 Interacts With miR-181a to modulate glioma growth and resistance to TMZ through PTEN pathway. J Cell Biochem 118(7):1889–1899. https://doi.org/10.1002/jcb.25910

    Article  CAS  PubMed  Google Scholar 

  25. Wang W, Zhao Z, Yang F, Wang H, Wu F, Liang T, Yan X, Li J et al (2018) An immune-related lncRNA signature for patients with anaplastic gliomas. J Neurooncol 136(2):263–271. https://doi.org/10.1007/s11060-017-2667-6

    Article  CAS  PubMed  Google Scholar 

  26. Williams GT, Farzaneh F (2012) Are snoRNAs and snoRNA host genes new players in cancer? Nat Rev Cancer 12(2):84–88. https://doi.org/10.1038/nrc3195

    Article  CAS  PubMed  Google Scholar 

  27. Sun Y, Wei G, Luo H, Wu W, Skogerbo G, Luo J, Chen R (2017) The long noncoding RNA SNHG1 promotes tumor growth through regulating transcription of both local and distal genes. Oncogene 36(49):6774–6783. https://doi.org/10.1038/onc.2017.286

    Article  CAS  PubMed  Google Scholar 

  28. Zhang PF, Wang F, Wu J, Wu Y, Huang W, Liu D, Huang XY, Zhang XM et al (2019) LncRNA SNHG3 induces EMT and sorafenib resistance by modulating the miR-128/CD151 pathway in hepatocellular carcinoma. J Cell Physiol 234(3):2788–2794. https://doi.org/10.1002/jcp.27095

    Article  CAS  PubMed  Google Scholar 

  29. Teng L, Feng YC, Guo ST, Wang PL, Qi TF, Yue YM, Wang SX, Zhang SN et al (2021) The pan-cancer lncRNA PLANE regulates an alternative splicing program to promote cancer pathogenesis. Nat Commun 12(1):3734. https://doi.org/10.1038/s41467-021-24099-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Zhou X, Liu X, Yang X, Wang L, Hong Y, Lian K, Qiu G, Shang X et al (2021) Tumor progress intercept by intervening in Caveolin-1 related intercellular communication via ROS-sensitive c-Myc targeting therapy. Biomaterials 275:120958. https://doi.org/10.1016/j.biomaterials.2021.120958

    Article  CAS  PubMed  Google Scholar 

  31. Chen L, He M, Zhang M, Sun Q, Zeng S, Zhao H, Yang H, Liu M et al (2021) The Role of non-coding RNAs in colorectal cancer, with a focus on its autophagy. Pharmacol Ther 226:107868. https://doi.org/10.1016/j.pharmthera.2021.107868

    Article  CAS  PubMed  Google Scholar 

  32. Fremin C, Meloche S (2010) From basic research to clinical development of MEK1/2 inhibitors for cancer therapy. J Hematol Oncol 3:8. https://doi.org/10.1186/1756-8722-3-8

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Ullah R, Yin Q, Snell AH, Wan L (2021) RAF-MEK-ERK pathway in cancer evolution and treatment. Semin Cancer Biol. https://doi.org/10.1016/j.semcancer.2021.05.010

    Article  PubMed  Google Scholar 

  34. Chen XJ, Liu S, Han DM, Han DZ, Sun WJ, Zhao XC, Liang JQ, Yu L (2020) FUT8-AS1 inhibits the malignancy of melanoma through promoting miR-145-5p biogenesis and suppressing NRAS/MAPK signaling. Front Oncol 10:586085. https://doi.org/10.3389/fonc.2020.586085

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Contributions

Jian Xu designed this study; Zeyu Wu, Peng Lun, and Tao Ji performed the experiments; Jiaojiao Niu, Xiuyan Sun, and Xia Liu analyzed the data; Jian Xu wrote the manuscript. All the authors have revised this manuscript and approved the submission.

Corresponding author

Correspondence to Jian Xu.

Ethics declarations

Ethics Approval

All experiments were conducted with the approval of The Affiliated Hospital of Qingdao University.

Consent to Participate

All patients were informed of the study and signed the written consent.

Consent for Publication

The informed consent is obtained from study participants.

Conflict of Interest

The authors declare no competing interests.

Additional information

Publisher's Note

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

Supplementary Information

Below is the link to the electronic supplementary material.

Supplementary file1 (PDF 389 KB)

Rights and permissions

Springer Nature or its licensor 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

Wu, Z., Lun, P., Ji, T. et al. LncRNA SNHG25 Promotes Glioma Progression Through Activating MAPK Signaling. Mol Neurobiol 59, 6993–7005 (2022). https://doi.org/10.1007/s12035-022-03015-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12035-022-03015-x

Keywords

Navigation