SP1-induced LncRNA ZFPM2 Antisense RNA 1 (ZFPM2-AS1) Aggravates Glioma Progression Via the MiR-515-5p/Superoxide Dismutase 2 (SOD2) Axis

Overview

Journal Bioengineered

Date 2021 Jun 2

PMID 34077295

Citations 24

Authors

Yaxuan Zhang

Yin Zhang

Sen Wang

Qingquan Li

Boqiang Cao

Baosheng Huang

Tianlu Wang

Ruijuan Guo

Ning Liu

Affiliations

Soon will be listed here.

Abstract

Glioma is a common life-threatening tumor with high malignancy and high invasiveness. LncRNA ZFPM2 antisense RNA 1 (ZFPM2-AS1) was confirmed to be implicated in numerous tumors, while its biological function and mechanism have not been thoroughly understood in glioma. The gene expression was measured by RT-qPCR. Cell proliferation, cell cycle, and cell apoptosis of glioma cells were validated by CCK-8, colony formation, flow cytometry and TUNEL assays. The effect of ZFPM2-AS1 on tumor growth was verified by assay. The exploration on ZFPM2-AS1-mediated mechanism was carried out via ChIP, luciferase reporter, and RIP assays. In the present study, ZFPM2-AS1 was demonstrated as a highly-expressed lncRNA in glioma tissues and cells. ZFPM2-AS1 silencing suppressed cell proliferation and cell cycle, but facilitated cell apoptosis. In addition, the inhibitive effect of silenced ZFPM2-AS1 was also observed in tumor growth. Furthermore, we found that SP1 interacted with ZFPM2-AS1 promoter to transcriptionally activate ZFPM2-AS1 expression. Moreover, ZFPM2-AS1 was identified as a competing endogenous RNA (ceRNA) for miR-515-5p to target SOD2. Rescue assays verified that SOD2 overexpression partially abolished the suppressive impact of ZFPM2-AS1 silencing on glioma cell growth. In conclusion, this study corroborated the regulatory mechanism of SP1/ZFPM2-AS1/miR-515-5p/SOD2 axis in glioma, indicating that targeting ZFPM2-AS1 might be an effective way to treat glioma.

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References

Gusyatiner O, Hegi M . Glioma epigenetics: From subclassification to novel treatment options. Semin Cancer Biol. 2017; 51:50-58. DOI: 10.1016/j.semcancer.2017.11.010. View

Lu Q, Qian L, Zhou X . Developmental origins and oncogenic pathways in malignant brain tumors. Wiley Interdiscip Rev Dev Biol. 2019; 8(4):e342. PMC: 6565468. DOI: 10.1002/wdev.342. View

Liu J, Yao L, Zhang M, Jiang J, Yang M, Wang Y . Downregulation of LncRNA-XIST inhibited development of non-small cell lung cancer by activating miR-335/SOD2/ROS signal pathway mediated pyroptotic cell death. Aging (Albany NY). 2019; 11(18):7830-7846. PMC: 6781979. DOI: 10.18632/aging.102291. View

Kiran M, Chatrath A, Tang X, Keenan D, Dutta A . A Prognostic Signature for Lower Grade Gliomas Based on Expression of Long Non-Coding RNAs. Mol Neurobiol. 2018; 56(7):4786-4798. PMC: 6499716. DOI: 10.1007/s12035-018-1416-y. View

Zhang H, Liu S, Tang L, Ge J, Lu X . Long non-coding RNA (LncRNA) MRPL23-AS1 promotes tumor progression and carcinogenesis in osteosarcoma by activating Wnt/β-catenin signaling via inhibiting microRNA miR-30b and upregulating myosin heavy chain 9 (MYH9). Bioengineered. 2020; 12(1):162-171. PMC: 8806232. DOI: 10.1080/21655979.2020.1863014. View

Xu T, Liu X, Xia R, Yin L, Kong R, Chen W . SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer. Oncogene. 2015; 34(45):5648-61. DOI: 10.1038/onc.2015.18. View

Wang Z, Cai Q, Hu L, He C, Li J, Quan Z . Long noncoding RNA UCA1 induced by SP1 promotes cell proliferation via recruiting EZH2 and activating AKT pathway in gastric cancer. Cell Death Dis. 2017; 8(6):e2839. PMC: 5520878. DOI: 10.1038/cddis.2017.143. View

Li Q, Wu Q, Li Z, Hu Y, Zhou F, Zhai Z . LncRNA LINC00319 is associated with tumorigenesis and poor prognosis in glioma. Eur J Pharmacol. 2019; 861:172556. DOI: 10.1016/j.ejphar.2019.172556. View

Livak K, Schmittgen T . Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 2002; 25(4):402-8. DOI: 10.1006/meth.2001.1262. View

10.

Li J, Tang Z, Wang H, Wu W, Zhou F, Ke H . CXCL6 promotes non-small cell lung cancer cell survival and metastasis via down-regulation of miR-515-5p. Biomed Pharmacother. 2017; 97:1182-1188. DOI: 10.1016/j.biopha.2017.11.004. View

11.

Kane J . The Role of Brain Vasculature in Glioblastoma. Mol Neurobiol. 2019; 56(9):6645-6653. DOI: 10.1007/s12035-019-1561-y. View

12.

Zhou T, Wu L, Ma N, Tang F, Yu Z, Jiang Z . SOX9-activated FARSA-AS1 predetermines cell growth, stemness, and metastasis in colorectal cancer through upregulating FARSA and SOX9. Cell Death Dis. 2020; 11(12):1071. PMC: 7736271. DOI: 10.1038/s41419-020-03273-4. View

13.

Nan Y, Han L, Zhang A, Wang G, Jia Z, Yang Y . MiRNA-451 plays a role as tumor suppressor in human glioma cells. Brain Res. 2010; 1359:14-21. DOI: 10.1016/j.brainres.2010.08.074. View

14.

Jansen M, Yip S, Louis D . Molecular pathology in adult gliomas: diagnostic, prognostic, and predictive markers. Lancet Neurol. 2010; 9(7):717-26. PMC: 3079431. DOI: 10.1016/S1474-4422(10)70105-8. View

15.

Dong H, Wang W, Mo S, Chen R, Zou K, Han J . SP1-induced lncRNA AGAP2-AS1 expression promotes chemoresistance of breast cancer by epigenetic regulation of MyD88. J Exp Clin Cancer Res. 2018; 37(1):202. PMC: 6114182. DOI: 10.1186/s13046-018-0875-3. View

16.

Zhong B, Bian L, Wang G, Zhou Y, Chen Y, Peng F . Identification of key genes involved in HER2-positive breast cancer. Eur Rev Med Pharmacol Sci. 2016; 20(4):664-72. View

17.

Zhang W, Wu Y, Hou B, Wang Y, Deng D, Fu Z . A SOX9-AS1/miR-5590-3p/SOX9 positive feedback loop drives tumor growth and metastasis in hepatocellular carcinoma through the Wnt/β-catenin pathway. Mol Oncol. 2019; 13(10):2194-2210. PMC: 6763786. DOI: 10.1002/1878-0261.12560. View

18.

Lyv X, Wu F, Zhang H, Lu J, Wang L, Ma Y . Long Noncoding RNA ZFPM2-AS1 Knockdown Restrains the Development of Retinoblastoma by Modulating the MicroRNA-515/HOXA1/Wnt/β-Catenin Axis. Invest Ophthalmol Vis Sci. 2020; 61(6):41. PMC: 7415309. DOI: 10.1167/iovs.61.6.41. View

19.

Qadir M, Faheem A . miRNA: A Diagnostic and Therapeutic Tool for Pancreatic Cancer. Crit Rev Eukaryot Gene Expr. 2017; 27(3):197-204. DOI: 10.1615/CritRevEukaryotGeneExpr.2017019494. View

20.

He H, Wang Y, Ye P, Yi D, Cheng Y, Tang H . Long noncoding RNA ZFPM2-AS1 acts as a miRNA sponge and promotes cell invasion through regulation of miR-139/GDF10 in hepatocellular carcinoma. J Exp Clin Cancer Res. 2020; 39(1):159. PMC: 7427719. DOI: 10.1186/s13046-020-01664-1. View