Abstract
Glioma is a malignant brain tumor that accounts for 30% of all brain tumors and 80% of malignant brain tumors. This poor clinical outcome makes the study of molecular mechanisms in glioma as an urgent subject. However, the certain mechanism remains unclear. Long non-coding RNAs (lncRNAs) plays a key role in glioma development and progression. In the present study, we aimed to explore the potential mechanisms of lncRNA SNHG16 in glioma. The levels of lncRNA SNHG16 were qualified in both glioma tissues and cell lines using qRT-PCR assay. The ability of cell proliferation was tested via CCK-8 and colony formation assays. Transfections were performed to knockdown SNHG16 and its target gene p21. The cell cycles and cell apoptosis were evaluated using flow cytometry, and the expression of SNHG16, p21 and apoptosis biomarkers were qualified with qRT-PCR and western blot assays. The expression of SNHG16 were up-regulated in both glioma tissues and cell lines. Knockdown of SNHG16 was associated with poor proliferation, decreased monoclonal formation rates, but increased apoptosis rates, which also caused the high expression of p21. Moreover, p21 could mediate cell proliferation and monoclonal formation, promote cell apoptosis in glioma, which was negatively correlated with lncRNA SNHG16. The molecule mechanism experiments revealed that SNHG16 could not only inhibit the expression of p21 but also suppressed the level of caspase 3 and 9, while promoted cyclinD1 and cyclinB1 expression. lncRNA SNHG16 could promote the cell proliferation and inhibit the apoptosis of glioma through suppressing p21, indicating that lncRNA SNHG16 might be quite vital for the diagnosis and progression of glioma and could even be a novel therapeutic target for glioma.
Similar content being viewed by others
References
Pines A (2011) Hormone therapy and brain tumors. Climacteric 14(2):215–216
Yin CL et al (2014) The role of glioma stem cells in glioma tumorigenesis. Front Biosci (Landmark Ed) 19:818–824
Chen JW, Zhou CF, Lin ZX (2015) The influence of different classification standards of age groups on prognosis in high-grade hemispheric glioma patients. J Neurol Sci 356(1–2):148–152
Malzkorn B, Reifenberger G (2016) Practical implications of integrated glioma classification according to the World Health Organization classification of tumors of the central nervous system 2016. Curr Opin Oncol 28(6):494–501
Liu G et al (2018) Survival analysis for high-grade glioma patients who received comprehensive treatment. Zhong Nan Da Xue Xue Bao Yi Xue Ban 43(4):388–393
Li Y et al (2015) Construction and analysis of lncRNA-lncRNA synergistic networks to reveal clinically relevant lncRNAs in cancer. Oncotarget 6(28):25003–25016
Huarte M (2015) The emerging role of lncRNAs in cancer. Nat Med 21(11):1253–1261
Li X et al (2014) lncRNAs: insights into their function and mechanics in underlying disorders. Mutat Res Rev Mutat Res 762:1–21
Wang XP et al (2017) Long non-coding RNA PAR5 inhibits the proliferation and progression of glioma through interaction with EZH2. Oncol Rep 38(5):3177–3186
Cui Y et al (2017) Long noncoding RNA HOXA11-AS functions as miRNA sponge to promote the glioma tumorigenesis through targeting miR-140-5p. DNA Cell Biol 36(10):822–828
Ma CC et al (2016) Long non-coding RNA ATB promotes glioma malignancy by negatively regulating miR-200a. J Exp Clin Cancer Res 35(1):90
Li H et al (2016) Differential long noncoding RNA and mRNA expression in differentiated human glioblastoma stem cells. Mol Med Rep 14(3):2067–2076
Yang BY et al (2018) Long non-coding RNA SNHG16 contributes to glioma malignancy by competitively binding miR-20a-5p with E2F1. J Biol Regul Homeost Agents 32(2):251–261
Yan L et al (2017) Identification of lymph node metastasis-related microRNAs in lung adenocarcinoma and analysis of the underlying mechanisms using a bioinformatics approach. Exp Biol Med (Maywood) 242(7):709–717
Lu YF et al (2018) LncRNA SNHG16 functions as an oncogene by sponging MiR-4518 and up-regulating PRMT5 expression in glioma. Cell Physiol Biochem 45(5):1975–1985
Liu K et al (2017) LncRNA SNHG15 contributes to proliferation, invasion and autophagy in osteosarcoma cells by sponging miR-141. J Biomed Sci 24(1):46
Chao Y et al (2015) Mst1 regulates glioma cell proliferation via the AKT/mTOR signaling pathway. J Neuro-Oncol 121(2):279–288
Takano N et al (2014) Decreased expression of cystathionine beta-synthase promotes glioma tumorigenesis. Mol Cancer Res 12(10):1398–1406
Sun J et al (2018) RUNX3 inhibits glioma survival and invasion via suppression of the betacatenin/TCF-4 signaling pathway. J Neuro-Oncol 140(1):15–26
Hochberg FH et al (2014) Glioma diagnostics and biomarkers: an ongoing challenge in the field of medicine and science. Expert Rev Mol Diagn 14(4):439–452
Hottinger AF, Hegi ME, Baumert BG (2016) Current management of low-grade gliomas. Curr Opin Neurol 29(6):782–788
Goldbrunner R et al (2018) The treatment of gliomas in adulthood. Dtsch Arztebl Int 115(20–21):356–364
Hart MG et al (2013) Temozolomide for high grade glioma. Cochrane Database Syst Rev 4(4):CD007415
Zhang X et al (2014) Combination of photodynamic therapy and temozolomide on glioma in a rat C6 glioma model. Photodiagn Photodyn Ther 11(4):603–612
Han X et al (2018) LncRNA TUG1 affects cell viability by regulating glycolysis in osteosarcoma cells. Gene 674:87–92
Yang Q et al (2018) Long non-coding RNA PVT1 promotes cell proliferation and invasion through regulating miR-133a in ovarian cancer. Biomed Pharmacother 106:61–67
Almnaseer ZA, Mourtada-Maarabouni M (2018) Long noncoding RNA MIAT regulates apoptosis and the apoptotic response to chemotherapeutic agents in breast cancer cell lines. Biosci Rep 38(4):BSR20180704
Kaikkonen MU, Lam MT, Glass CK (2011) Non-coding RNAs as regulators of gene expression and epigenetics. Cardiovasc Res 90(3):430–440
Tsai MC et al (2010) Long noncoding RNA as modular scaffold of histone modification complexes. Science 329(5992):689–693
Liu Y et al (2015) Over-expression of lncRNA DANCR is associated with advanced tumor progression and poor prognosis in patients with colorectal cancer. Int J Clin Exp Pathol 8(9):11480–11484
Zhang X et al (2012) Long non-coding RNA expression profiles predict clinical phenotypes in glioma. Neurobiol Dis 48(1):1–8
Wei N, Wei H, Zhang H (2018) Long non-coding RNA ZEB1-AS1 promotes glioma cell proliferation, migration and invasion through regulating miR-577. Eur Rev Med Pharmacol Sci 22(10):3085–3093
Acknowledgments
We would like to give our sincere gratitude to the reviewers for their constructive comments.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Ethical Approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Informed Consent
Informed consent was obtained from all individual participants included in the study.
Conflict of Interest
The authors declares that they have no conflict of interest.
Additional information
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Zhou, XY., Liu, H., Ding, ZB. et al. lncRNA SNHG16 Exerts Oncogenic Functions in Promoting Proliferation of Glioma Through Suppressing p21. Pathol. Oncol. Res. 26, 1021–1028 (2020). https://doi.org/10.1007/s12253-019-00648-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12253-019-00648-7