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The LncRNA RP11-279C4.1 Enhances the Malignant Behaviour of Glioma Cells and Glioma Stem-Like Cells by Regulating the miR-1273g-3p/CBX3 Axis

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Abstract

Glioma is the most common type of solid tumour affecting the central nervous system, and the survival rate of patients with glioma is low. However, the mechanism associated with glioma progression remains unclear. Growing evidence suggests that lncRNAs play essential roles in the initiation and progression of tumours, including gliomas. In the present study, we identified and verified the expression of the novel lncRNA RP11-279C4.1 by analyzing the TANRIC database and performing qRT-PCR assays, the results of which revealed its upregulation in glioma tissues and cell lines. The results of multiple functional experiments demonstrated that RP11-279C4.1 knockdown inhibited glioma malignant phenotypes, including cell proliferation, migration, invasion and cell self-renew ability in vitro. In addition, RP11-279C4.1 downregulation suppressed tumour growth in vivo. Mechanistically, RP11-279C4.1 induced CBX3 activation via competitively sponging miR-1273g-3p, and rescue assay results confirmed the importance of the RP11-279C4.1/miR-1273g-3p/CBX3 axis. Overall, the results of our present study demonstrated that RP11-279C4.1 functions as an oncogene that promotes tumour progression by modulating the miR-1273g-3p/CBX3 axis in glioma, suggesting that RP11-279C4.1 may be a novel therapeutic target for glioma.

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

References

  1. Theeler BJ, Dalal Y, Monje M, Shilatifard A, Suvà ML, Aboud O, Camphausen K, Cordova C et al (2020) Comprehensive Oncology Network Evaluating Rare CNS Tumors-Histone Mutated Midline Glioma Workshop Proceedings. Neurooncol Adv 2(1):vdaa007. https://doi.org/10.1093/noajnl/vdaa007

    Article  PubMed  PubMed Central  Google Scholar 

  2. Medikonda R, Dunn G, Rahman M, Fecci P, Lim M (2020) A review of glioblastoma immunotherapy. J Neurooncol. https://doi.org/10.1007/s11060-020-03448-1

  3. Noch EK, Ramakrishna R, Magge R (2018) Challenges in the treatment of glioblastoma: multisystem mechanisms of therapeutic resistance. World Neurosurg. 116:505–517. https://doi.org/10.1016/j.wneu.2018.04.022.

    Article  PubMed  Google Scholar 

  4. Tykocki T, Eltayeb M (2018) Ten-year survival in glioblastoma. A systematic review. J Clin Neurosci. 54:7–13. https://doi.org/10.1016/j.jocn.2018.05.002.

    Article  PubMed  Google Scholar 

  5. Molinaro AM, Taylor JW, Wiencke JK, Wrensch MR (2019) Genetic and molecular epidemiology of adult diffuse glioma. Nat Rev Neurol. 15(7):405–417. https://doi.org/10.1038/s41582-019-0220-2.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Gimple RC, Bhargava S, Dixit D, Rich JN (2019) Glioblastoma stem cells: lessons from the tumor hierarchy in a lethal cancer. Genes Dev. 33(11-12):591–609. https://doi.org/10.1101/gad.324301.119.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Hombach S, Kretz M (2016) Non-coding RNAs: classification, biology and functioning. Adv Exp Med Biol. 937:3–17. https://doi.org/10.1007/978-3-319-42059-2_1.

    Article  CAS  PubMed  Google Scholar 

  8. Wu J, Guo X, Xu D, Zhang H (2020) LINC00662 sponges miR-107 accelerating the invasiveness and proliferation of glioma cells. J Cancer. 11(19):5700–5712. https://doi.org/10.7150/jca.46381

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Yu H, Xu A, Wu B, Wang M, Chen Z (2020) Long noncoding RNA NEAT1 promotes progression of glioma as a ceRNA by sponging miR-185-5p to stimulate DNMT1/mTOR signaling. J Cell Physiol. https://doi.org/10.1002/jcp.29644

  10. Liu ZZ, Tian YF, Wu H, Ouyang SY, Kuang WL (2020) LncRNA H19 promotes glioma angiogenesis through miR-138/HIF-1α/VEGF axis. Neoplasma. 67(1):111–118. https://doi.org/10.4149/neo_2019_190121N61.

    Article  CAS  PubMed  Google Scholar 

  11. Zhang Y, Mou C, Shang M, Jiang M, Xu C (2020) Long noncoding RNA RP11-626G11.3 promotes the progression of glioma through miR-375-SP1 axis. Mol Carcinog. 59(5):492–502. https://doi.org/10.1002/mc.23173.

    Article  CAS  PubMed  Google Scholar 

  12. Xia H, Liu Y, Wang Z, Zhang W, Qi M, Qi B, Jiang X (2020) Long noncoding RNA HOTAIRM1 maintains tumorigenicity of glioblastoma stem-like cells through regulation of HOX gene expression. Neurotherapeutics. 17(2):754–764. https://doi.org/10.1007/s13311-019-00799-0.

    Article  CAS  PubMed  Google Scholar 

  13. Zheng Y, Miao Y, Xie J, Lin Y, Yao Q, Cai J, Yang X (2020) Long noncoding RNA lysophospholipase-like 1-2 as ceRNA modulates glioma metastasis by regulating miR-217/YWHAG. Am J Transl Res. 12(8):4204–4215

    CAS  PubMed  PubMed Central  Google Scholar 

  14. Zhang G, Li S, Lu J, Ge Y, Wang Q, Ma G, Zhao Q, Wu D et al (2018) LncRNA MT1JP functions as a ceRNA in regulating FBXW7 through competitively binding to miR-92a-3p in gastric cancer. Mol Cancer. 17(1):87. https://doi.org/10.1186/s12943-018-0829-6

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kong X, Duan Y, Sang Y, Li Y, Zhang H, Liang Y, Liu Y, Zhang N et al (2019) LncRNA-CDC6 promotes breast cancer progression and function as ceRNA to target CDC6 by sponging microRNA-215. J Cell Physiol 234(6):9105–9117. https://doi.org/10.1002/jcp.27587

    Article  CAS  PubMed  Google Scholar 

  16. Wang Y, Song B, Zhu L, Zhang X (2019) Long non-coding RNA, LINC01614 as a potential biomarker for prognostic prediction in breast cancer. PeerJ. 7:e7976. https://doi.org/10.7717/peerj.7976.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Younis M, Faming W, Hongyan Z, Mengmeng T, Hang S, Liudi Y (2019) Iguratimod encapsulated PLGA-NPs improves therapeutic outcome in glioma, glioma stem-like cells and temozolomide resistant glioma cells. Nanomedicine. 22:102101. https://doi.org/10.1016/j.nano.2019.102101.

    Article  CAS  PubMed  Google Scholar 

  18. National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals (2011) Guide for the Care and Use of Laboratory Animals, 8th edn. National Academies Press, Washington, DC, pp. 11–104

    Google Scholar 

  19. Song H, Zhang Y, Liu N, Zhang D, Wan C, Zhao S, Kong Y, Yuan L (2016) Let-7b inhibits the malignant behavior of glioma cells and glioma stem-like cells via downregulation of E2F2. J Physiol Biochem 72(4):733–744. https://doi.org/10.1007/s13105-016-0512-6

    Article  CAS  PubMed  Google Scholar 

  20. Zhang B, Chen J, Cui M, Jiang Y (2020) LncRNA ZFAS1/miR-1271-5p/HK2 promotes glioma development through regulating proliferation, migration, invasion and apoptosis. Neurochem Res. https://doi.org/10.1007/s11064-020-03131-x

  21. Zhang X, Niu W, Mu M, Hu S, Niu C (2020) Long non-coding RNA LPP-AS2 promotes glioma tumorigenesis via miR-7-5p/EGFR/PI3K/AKT/c-MYC feedback loop. J Exp Clin Cancer Res. 39(1):196. https://doi.org/10.1186/s13046-020-01695-8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Mu M, Niu W, Zhang X, Hu S, Niu C (2020) LncRNA BCYRN1 inhibits glioma tumorigenesis by competitively binding with miR-619-5p to regulate CUEDC2 expression and the PTEN/AKT/p21 pathway. Oncogene. https://doi.org/10.1038/s41388-020-01466-x

  23. Zheng J, Wang B, Zheng R, Zhang J, Huang C, Zheng R, Huang Z, Qiu W et al (2020) Linc-RA1 inhibits autophagy and promotes radioresistance by preventing H2Bub1/USP44 combination in glioma cells. Cell Death Dis. 11(9):758. https://doi.org/10.1038/s41419-020-02977-x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Qi J, Wang Z, Zhao Z, Liu L (2020) EIF3J-AS1 promotes glioma cell growth via up-regulating ANXA11 through sponging miR-1343-3p. Cancer Cell Int. 20:428. https://doi.org/10.1186/s12935-020-01487-2

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wang B, Wang K, Jin T, Xu Q, He Y, Cui B, Wang Y (2020) NCK1-AS1 enhances glioma cell proliferation, radioresistance and chemoresistance via miR-22-3p/IGF1R ceRNA pathway. Biomed Pharmacother. 129:110395. https://doi.org/10.1016/j.biopha.2020.110395

    Article  CAS  PubMed  Google Scholar 

  26. Yu Y, Gao F, He Q, Li G, Ding G (2020) lncRNA UCA1 Functions as a ceRNA to promote prostate cancer progression via sponging miR143. Mol Ther Nucleic Acids. 19:751–758. https://doi.org/10.1016/j.omtn.2019.11.021.

    Article  CAS  PubMed  Google Scholar 

  27. Liang H, Su X, Wu Q, Shan H, Lv L, Yu T, Zhao X, Sun J et al (2020) LncRNA 2810403D21Rik/Mirf promotes ischemic myocardial injury by regulating autophagy through targeting Mir26a. Autophagy. 16(6):1077–1091. https://doi.org/10.1080/15548627.2019.1659610

    Article  CAS  PubMed  Google Scholar 

  28. Wu F, Liu F, Dong L, Yang H, He X, Li L, Zhao L, Jin S et al (2018) miR-1273g silences MAGEA3/6 to inhibit human colorectal cancer cell growth via activation of AMPK signaling. Cancer Lett. 435:1–9. https://doi.org/10.1016/j.canlet.2018.07.031.

    Article  CAS  PubMed  Google Scholar 

  29. Zhao Y, Du T, Du L, Li P, Li J, Duan W, Wang Y, Wang C (2019) Long noncoding RNA LINC02418 regulates MELK expression by acting as a ceRNA and may serve as a diagnostic marker for colorectal cancer. Cell Death Dis. 10(8):568. https://doi.org/10.1038/s41419-019-1804-x.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Chen LY, Cheng CS, Qu C, Wang P, Chen H, Meng ZQ, Chen Z (2018) CBX3 promotes proliferation and regulates glycolysis via suppressing FBP1 in pancreatic cancer. Biochem Biophys Res Commun. 500(3):691–697. https://doi.org/10.1016/j.bbrc.2018.04.137.

    Article  CAS  PubMed  Google Scholar 

  31. Fan Y, Li H, Liang X, Xiang Z (2017) CBX3 promotes colon cancer cell proliferation by CDK6 kinase-independent function during cell cycle. Oncotarget. 8(12):19934–19946. https://doi.org/10.18632/oncotarget.15253.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Liu J, Zhan Y, Wang J, Wang J, Guo J, Kong D (2020) lncRNA-SNHG17 promotes colon adenocarcinoma progression and serves as a sponge for miR-375 to regulate CBX3 expression. Am J Transl Res. 12(9):5283–5295

    CAS  PubMed  PubMed Central  Google Scholar 

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Funding

This study was supported by the Graduate Research and Innovation Projects of Jiangsu Province (KYCX19_0114).

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Authors

Contributions

LY and FW designed and supervised the study. FW, LZ and YL performed the in vitro and in vivo experiments. FW and QZ prepared the figs. YZ collected and analyzed the data. FW, YL and YS wrote the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Liudi Yuan.

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All procedures performed in this study were approved by the Research Ethics Committee of Southeast University (Nanjing, China) (20200701006, 01 July 2020).

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Not applicable.

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The authors declare no competing interests.

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Supplementary Information

Supplementary Figure S1

The relative expression of miR-1273g-3p in glioma tissues and cell lines. a qRT-PCR was performed to analysis the expression level of miR-1273g-3p in one normal cell line and glioma cell lines. b The relative miR-1273g-3p expression in differaent grades of glioma was examined by CGGA database. c The overall survival were created by analyzing Oncomine database and classifified according to high and low miR-1273g-3p expression. The data are expressed as the mean ± SD of triplicates of three independent experiments (*P < 0.05, **P < 0.01) (PNG 234 kb)

High Resolution Image (TIF 7003 kb)

Supplementary Figure S2

Overexpression of CBX3 partly rescued sh-RP11-279C4.1-induced inhibitory effects on proliferation of glioma. Colony formation assay was applied to evaluate the proliferation ability of U87 and U251 transfected with sh-NC, sh-RP11-279C4.1 and sh-RP11-279C4.1+pcDNA-CBX3. The data are expressed as the mean ± SD of triplicates of three independent experiments (*P < 0.05, **P < 0.01) (PNG 137 kb)

High Resolution Image (TIF 6769 kb)

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Wang, F., Zhang, L., Luo, Y. et al. The LncRNA RP11-279C4.1 Enhances the Malignant Behaviour of Glioma Cells and Glioma Stem-Like Cells by Regulating the miR-1273g-3p/CBX3 Axis. Mol Neurobiol 58, 3362–3373 (2021). https://doi.org/10.1007/s12035-021-02337-6

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