AccScience Publishing / EJMO / Online First / DOI: 10.36922/EJMO025510529
Submit to EJMO
Cite this article
5
Download
38
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
ORIGINAL RESEARCH ARTICLE

Long non-coding RNA MEG3 acts as a tumor inhibitor in human cancer

Yan Li1 ,  Yan Wang1*
Show Less
1 Department of Obstetrics and Gynecology, First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, China
EJMO, 025510529 https://doi.org/10.36922/EJMO025510529
Received: 18 December 2025 | Revised: 8 January 2026 | Accepted: 13 January 2026 | Published online: 13 February 2026
© 2026 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
Download PDF
XML
Cite
Abstract

Introduction: The role of MEG3 in human cancers remains incompletely understood.

Objective: In this study, we elucidate the tumor-suppressive function of MEG3 across multiple cancer types, including ovarian cancer.

Methods: We systematically analyzed MEG3 expression in both tumor and normal tissues using publicly available databases to investigate its regulatory implications for clinical prognosis, pathological stage, tumor purity, chemotherapy resistance, and immune cell infiltration. Furthermore, we explored the underlying regulatory mechanisms of MEG3 by predicting upstream transcription factors and conducting downstream functional enrichment analyses.

Results: Our findings demonstrate that MEG3 expression is significantly downregulated in tumor tissues compared to normal counterparts. Moreover, MEG3 expression is associated with overall survival, relapse-free survival, and tumor, node, metastasis staging across several malignancies. Notably, higher MEG3 expression is negatively correlated with tumor purity and chemotherapy resistance. We identified SPI1 as a potential upstream transcription factor regulating MEG3 expression. Functional enrichment analysis revealed that MEG3 may exert its tumor-suppressive effects through the modulation of the Hippo signaling pathway. In addition, MEG3 methylation was found to regulate the expression of genes involved in the cell cycle of ovarian cancer cells and modulate the ovarian cancer microenvironment by influencing immune cell infiltration.

Conclusion: These results collectively suggest that MEG3 may serve as a tumor suppressor and represent a promising therapeutic target in human cancers.

Keywords
MEG3
Ovarian cancer
Suppressor
Tumor purity
Immune infiltration
Funding
This work was supported by The Foundation of First Affiliated Hospital of Harbin Medical University (2023M19) and Heilongjiang Province Jizhong Medical Aid Charity Foundation (2020HX029).
Conflict of interest
The authors declare they have no competing interests.
References
  1. Liu SJ, Dang HX, Lim DA, Feng FY, Maher CA. Long noncoding RNAs in cancer metastasis. Nat Rev Cancer. 2021;21(7):446-460. doi: 10.1038/s41568-021-00353-1

 

  1. Qian X, Yang J, Qiu Q, et al. LCAT3, a novel m6A-regulated long non-coding RNA, plays an oncogenic role in lung cancer via binding with FUBP1 to activate c-MYC. J Hematol Oncol. 2021;14(1):112. doi: 10.1186/s13045-021-01123-0

 

  1. Liu K, Gao L, Ma X, et al. Long non-coding RNAs regulate drug resistance in cancer. Mol Cancer. 2020;19(1):54. doi: 10.1186/s12943-020-01162-0

 

  1. Hu Q, Egranov SD, Lin C, Yang L. Long noncoding RNA loss in immune suppression in cancer. Pharmacol Ther. 2020;213:107591. doi: 10.1016/j.pharmthera.2020.107591

 

  1. Sherpa C, Rausch JW, Le Grice SF. Structural characterization of maternally expressed gene 3 RNA reveals conserved motifs and potential sites of interaction with polycomb repressive complex 2. Nucleic Acids Res. 2018;46(19):10432-10447. doi: 10.1093/nar/gky722

 

  1. Dong S, Ma M, Li M, et al. LncRNA MEG3 regulates breast cancer proliferation and apoptosis through miR-141-3p/ RBMS3 axis. Genomics. 2021;113(4):1689-1704. doi: 10.1016/j.ygeno.2021.04.015

 

  1. Buttarelli M, De Donato M, Raspaglio G, et al. Clinical value of lncRNA MEG3 in high-grade serous ovarian cancer. Cancers (Basel). 2020;12(4):966. doi: 10.3390/cancers12040966

 

  1. Ying L, Huang Y, Chen H, et al. Downregulated MEG3 activates autophagy and increases cell proliferation in bladder cancer. Mol Biosyst. 2013;9(3):407-411. doi: 10.1039/c2mb25386k

 

  1. Xiu YL, Sun KX, Chen X, et al. Upregulation of the lncRNA Meg3 induces autophagy to inhibit tumorigenesis and progression of epithelial ovarian carcinoma by regulating activity of ATG3. Oncotarget. 2017;8(19):31714-31725. doi: 10.18632/oncotarget.15955

 

  1. Uroda T, Anastasakou E, Rossi A, et al. Conserved pseudoknots in lncRNA MEG3 are essential for stimulation of the p53 pathway. Mol Cell. 2019;75(5):982-995.e9. doi: 10.1016/j.molcel.2019.07.025

 

  1. Mondal T, Subhash S, Vaid R, et al. MEG3 long noncoding RNA regulates the TGF-β pathway genes through formation of RNA-DNA triplex structures. Nat Commun. 2015;6:7743. doi: 10.1038/ncomms8743

 

  1. Shan G, Tang T, Xia Y, Qian HJ. MEG3 interacted with miR- 494 to repress bladder cancer progression through targeting PTEN. J Cell Physiol. 2020;235(2):1120-1128. doi: 10.1002/jcp.29025

 

  1. Huang C, Liao X, Jin H, et al. MEG3, as a competing endogenous RNA, binds with miR-27a to promote PHLPP2 protein translation and impairs bladder cancer invasion. Mol Ther Nucleic Acids. 2019;16:51-62. doi: 10.1016/j.omtn.2019.01.014

 

  1. Dai Y, Wan Y, Qiu M, et al. lncRNA MEG3 suppresses the tumorigenesis of hemangioma by sponging miR-494 and regulating PTEN/PI3K/AKT pathway. Cell Physiol Biochem. 2018;51(6):2872-2886. doi: 10.1159/000496040

 

  1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7-30. doi: 10.3322/caac.21590

 

  1. Bhan A, Soleimani M, Mandal SS. Long noncoding RNA and cancer: A new paradigm. Cancer Res. 2017;77(15):3965-3981. doi: 10.1158/0008-5472.CAN-16-2634

 

  1. Huang GQ, Ke ZP, Hu HB, Gu B. Co-expression network analysis of long noncoding RNAs (IncRNAs) and cancer genes revealsSFTA1P and CASC2abnormalities in lung squamous cell carcinoma. Cancer Biol Ther. 2017;18(2):115-122. doi: 10.1080/15384047.2017.1281494

 

  1. Al-Rugeebah A, Alanazi M, Parine NR. MEG3: An oncogenic long non-coding RNA in different cancers. Pathol Oncol Res. 2019;25(3):859-874. doi: 10.1007/s12253-019-00614-3

 

  1. Dong P, Xiong Y, Yue J, et al. Exploring lncRNA-mediated regulatory networks in endometrial cancer cells and the tumor microenvironment: Advances and challenges. Cancers (Basel). 2019;11(2):234. doi: 10.3390/cancers11020234

 

  1. Guo Q, Qian Z, Yan D, Li L, Huang L. LncRNA-MEG3 inhibits cell proliferation of endometrial carcinoma by repressing Notch signaling. Biomed Pharmacother. 2016;82:589-594. doi: 10.1016/j.biopha.2016.02.049

 

  1. Wang J, Xu W, He Y, Xia Q, Liu S. LncRNA MEG3 impacts proliferation, invasion, and migration of ovarian cancer cells through regulating PTEN. Inflamm Res. 2018;67(11-12):927-936. doi: 10.1007/s00011-018-1186-z

 

  1. Wang L, Yu M, Zhao S. lncRNA MEG3 modified epithelial-mesenchymal transition of ovarian cancer cells by sponging miR-219a-5p and regulating EGFR. J Cell Biochem. 2019;120(10):17709-17722. doi: 10.1002/jcb.29037

 

  1. Liu Y, Xu Y, Ding L, Yu L, Zhang B, Wei D. LncRNA MEG3 suppressed the progression of ovarian cancer via sponging miR-30e-3p and regulating LAMA4 expression. Cancer Cell Int. 2020;20:181. doi: 10.1186/s12935-020-01259-y

 

  1. Samuels LD. Actinomycin and its effects. Influence on an effector pathway for hormonal control. N Engl J Med. 1964;271:1301-1308.CONTD. doi: 10.1056/NEJM196412172712507

 

  1. Cortes CL, Veiga SR, Almacellas E, et al. Effect of low doses of actinomycin D on neuroblastoma cell lines. Mol Cancer. 2016;15:1. doi: 10.1186/s12943-015-0489-8

 

  1. Even C, Pautier P, Duvillard P, et al. Actinomycin D, cisplatin, and etoposide regimen is associated with almost universal cure in patients with high-risk gestational trophoblastic neoplasia. Eur J Cancer. 2014;50(12):2082-2089. doi: 10.1016/j.ejca.2014.05.002

 

  1. Markasz L, Kis LL, Stuber G, et al. Hodgkin-lymphoma-derived cells show high sensitivity to dactinomycin and paclitaxel. Leuk Lymphoma. 2007;48(9):1835-1845. doi: 10.1080/10428190701559132

 

  1. Pontes JE, Magoss I, Staubitz W, Murphy GP. The treatment of stages I and II nonseminomatous testicular tumors: The Buffalo experience from 1970 to 1979. J Urol. 1982;128(6):1201-1204. doi: 10.1016/s0022-5347(17)53423-0

 

  1. Farber S, D’Angio G, Evans A, Mitus A. Clinical studies of actinomycin D with special reference to Wilms’ tumor in children. 1960. J Urol. 2002;168(6):2560-2562; discussion 2563. doi: 10.1097/01.ju.0000042140.76846.d9

 

  1. Jareemit N, Horowitz NS, Goldstein DP, Berkowitz RS, Elias KM. EMA vs EMACO in the treatment of gestational trophoblastic neoplasia. Gynecol Oncol. 2020;158(1):99-104. doi: 10.1016/j.ygyno.2020.04.699

 

  1. Zhao B, Tumaneng K, Guan KL. The Hippo pathway in organ size control, tissue regeneration and stem cell self-renewal. Nat Cell Biol. 2011;13(8):877-883. doi: 10.1038/ncb2303

 

  1. Li FL, Guan KL. The two sides of Hippo pathway in cancer. Semin Cancer Biol. 85:33-42. doi: 10.1016/j.semcancer.2021.07.006

 

  1. Kulkarni A, Chang MT, Vissers JHA, Dey A, Harvey KF. The hippo pathway as a driver of select human cancers. Trends Cancer. 2020;6(9):781-796. doi: 10.1016/j.trecan.2020.04.004

 

  1. Xie Q, Chen C, Li H, et al. miR-3687 overexpression promotes bladder cancer cell growth by inhibiting the negative effect of FOXP1 on cyclin E2 transcription. Mol Ther. 2019;27(5):1028-1038.doi: 10.1016/j.ymthe.2019.03.006

 

  1. Li W, Cao J, Liu J, et al. Downregulation of CDKL1 suppresses neuroblastoma cell proliferation, migration and invasion. Cell Mol Biol Lett. 2019;24:19. doi: 10.1186/s11658-019-0139-z

 

  1. Qin C, Ren L, Ji M, et al. CDKL1 promotes tumor proliferation and invasion in colorectal cancer. Onco Targets Ther. 2017;10:1613-1624. doi: 10.2147/OTT.S133014

 

  1. Hanahan D, Weinberg RA. Hallmarks of cancer: The next generation. Cell. 2011;144(5):646-674. doi: 10.1016/j.cell.2011.02.013

 

  1. Junttila MR, de Sauvage FJ. Influence of tumour micro-environment heterogeneity on therapeutic response. Nature. 2013;501(7467):346-354. doi: 10.1038/nature12626

 

  1. Xiong Y, Xiong Z, Cao H, Li C, Wanggou S, Li X. Multi-dimensional omics characterization in glioblastoma identifies the purity-associated pattern and prognostic gene signatures. Cancer Cell Int. 2020;20:37. doi: 10.1186/s12935-020-1116-3

 

  1. Morvan MG, Lanier LL. NK cells and cancer: You can teach innate cells new tricks. Nat Rev Cancer. 2016;16(1):7-19. doi: 10.1038/nrc.2015.5

 

  1. Choucair K, Duff JR, Cassidy CS, et al. Natural killer cells: A review of biology, therapeutic potential and challenges in treatment of solid tumors. Future Oncol. 2019;15(26):3053-3069. doi: 10.2217/fon-2019-0116

 

  1. Mantovani A, Marchesi F, Malesci A, Laghi L, Allavena P. Tumour-associated macrophages as treatment targets in oncology. Nat Rev Clin Oncol. 2017;14(7):399-416. doi: 10.1038/nrclinonc.2016.217

 

  1. Wang SS, Liu W, Ly D, Xu H, Qu L, Zhang L. Tumor-infiltrating B cells: Their role and application in anti-tumor immunity in lung cancer. Cell Mol Immunol. 2019;16(1):6-18. doi: 10.1038/s41423-018-0027-x

 

  1. Haabeth OA, Lorvik KB, Hammarstrom C, et al. Inflammation driven by tumour-specific Th1 cells protects against B-cell cancer. Nat Commun. 2011;2:240. doi: 10.1038/ncomms1239

 

  1. Merad M, Salmon H. Cancer: A dendritic-cell brake on antitumour immunity. Nature. 2015;523(7560):294-295. doi: 10.1038/523294a

 

  1. Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883-899. doi: 10.1016/j.cell.2010.01.025

 

  1. Zhang H, Dai Z, Wu W, et al. Regulatory mechanisms of immune checkpoints PD-L1 and CTLA-4 in cancer. J Exp Clin Cancer Res. 2021;40(1):184. doi: 10.1186/s13046-021-01987-7

 

  1. Rowshanravan B, Halliday N, Sansom DM. CTLA- 4: A moving target in immunotherapy. Blood. 2018;1 31(1):58-67. doi: 10.1182/blood-2017-06-741033

 

  1. Solinas C, De Silva P, Bron D, et al. Significance of TIM3 expression in cancer: From biology to the clinic. Semin Oncol. 2019;46(4-5):372-379. doi: 10.1053/j.seminoncol.2019.08.005

 

  1. Friedlaender A, Addeo A, Banna G. New emerging targets in cancer immunotherapy: The role of TIM3. ESMO Open. 2019;4(Suppl 3):e000497. doi: 10.1136/esmoopen-2019-000497
Next article in this issue
Share
Back to top
Eurasian Journal of Medicine and Oncology, Electronic ISSN: 2587-196X Print ISSN: 2587-2400, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept