Accumulating evidence has proved that long non-coding RNAs (lncRNAs) are involved in progression of glioma. Nevertheless, the role of TUBA4B in glioma remains unclear.

Material and methods:
The expression of the target gene was measured by quantitative RT-PCR. The prognostic role of TUBA4B was analyzed by Meier survival analysis. Cell proliferation, colony formation, apoptosis, cell cycle, migration and invasion were detected by MTS, soft agar colony forming assay, flow cytometry, and transwell assay. The target interaction of the target gene was validated by the luciferase reporter assay, biotin pull-down assay, and RNA immunoprecipitation.

We found that the expression of TUBA4B was lower in glioma tissues and cells. Moreover, patients with a low TUBA4B expression level exhibited poorer prognosis than those with high TUBA4B expression. Meanwhile, ROC analysis revealed that TUBA4B had diagnostic value to distinguish tumor patients from the healthy population. Overexpression of TUBA4B prohibited the malignancy of glioma, such as inhibition of proliferation, decrease of colony formation, arrest of the cell cycle, decline of migration and invasion, and promotion of cell apoptosis. In addition, we found that TUBA4B directly interacted with miR-183 and negatively regulated the expression of miR-183. We also observed that SMAD4 was a downriver target of miR-183 and TUBA4B subsequently exerted its tumor-suppressive effects by coordinating the expression of SMAD4 in glioma.

This study revealed for the first time that TUBA4B could be a tumor suppressor gene in glioma by adjustment of the TUBA4B/miR-183/SMAD4 axis, which may provide a useful prognostic biomarker and promising therapeutic target for glioma treatment.

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J Clin 2019; 69: 7-34.
Chen W, Zheng R, Baade PD, et al. Cancer statistics in China, 2015. CA Cancer J Clin 2016; 66: 115-32.
Bush NA, Chang SM, Berger MS. Current and future strategies for treatment of glioma. Neurosurg Rev 2017; 40: 1-14.
Wahlestedt C. Targeting long non-coding RNA to therapeutically upregulate gene expression. Nat Rev Drug Discov 2013; 12: 433-46.
Hu X, Shen G, Lu X, Ding G, Shen L. Identification of key proteins and lncRNAs in hypertrophic cardiomyopathy by integrated network analysis. Arch Med Sci 2019; 15: 484-97.
Arun G, Diermeier SD, Spector DL. Therapeutic targeting of long non-coding RNAs in cancer. Trends Mol Med 2018; 24: 257-77.
Bhan A, Soleimani M, Mandal SS. Long noncoding RNA and cancer: a new paradigm. Cancer Res 2017; 77: 3965-81.
Han X, Xu Z, Tian G, et al. Suppression of the long non-coding RNA MALAT-1 impairs the growth and migration of human tongue squamous cell carcinoma SCC4 cells. Arch Med Sci 2019; 15: 992-1000.
Peng Z, Liu C, Wu M. New insights into long noncoding RNAs and their roles in glioma. Mol Cancer 2018; 17: 61.
Luo Z, Pan J, Ding Y, Zhang YS, Zeng Y. The function and clinical relevance of lncRNA UBE2CP3-001 in human gliomas. Arch Med Sci 2018; 14: 1308-20.
Li C, Zheng H, Hou W, et al. Long non-coding RNA linc00645 promotes TGF-beta-induced epithelial-mesenchymal transition by regulating miR-205-3p-ZEB1 axis in glioma. Cell Death Dis 2019; 10: 717.
Dong ZQ, Guo ZY, Xie J. The lncRNA EGFR-AS1 is linked to migration, invasion and apoptosis in glioma cells by targeting miR-133b/RACK1. Biomed Pharmacother 2019; 118: 109292.
Guo J, Li Y, Duan H, Yuan L. LncRNA TUBA4B functions as a competitive endogenous RNA to inhibit gastric cancer progression by elevating PTEN via sponging miR-214 and miR-216a/b. Cancer Cell Int 2019; 19: 156.
Liu AX, Yang F, Huang L, Zhang LY, Zhang JR, Zheng RN. Long non-coding RNA tubulin alpha 4B (TUBA4B) inhibited breast cancer proliferation and invasion by directly targeting miR-19. Eur Rev Med Pharmacol Sci 2019; 23: 708-15.
Zhu FF, Zheng FY, Wang HO, Zheng JJ, Zhang Q. Downregulation of lncRNA TUBA4B is associated with poor prognosis for epithelial ovarian cancer. Pathol Oncol Res 2018; 24: 419-25.
Chen J, Hu L, Wang J, et al. Low expression LncRNA TUBA4B is a poor predictor of prognosis and regulates cell proliferation in non-small cell lung cancer. Pathol Oncol Res 2017; 23: 265-70.
Shi D, Wu F, Mu S, et al. LncRNA AFAP1-AS1 promotes tumorigenesis and epithelial-mesenchymal transition of osteosarcoma through RhoC/ROCK1/p38MAPK/Twist1 signaling pathway. J Exp Clin Cancer Res 2019; 38: 375.
Li J, He M, Xu W, Huang S. LINC01354 interacting with hnRNP-D contributes to the proliferation and metastasis in colorectal cancer through activating Wnt/beta-catenin signaling pathway. J Exp Clin Cancer Res 2019; 38: 161.
Xu R, Han Y. Long non-coding RNA FOXF1 adjacent non-coding developmental regulatory RNA inhibits growth and chemotherapy resistance in non-small cell lung cancer. Arch Med Sci 2019; 15: 1539-46.
Shao S, Tian J, Zhang H, Wang S. LncRNA myocardial infarction-associated transcript promotes cell proliferation and inhibits cell apoptosis by targeting miR-330-5p in epithelial ovarian cancer cells. Arch Med Sci 2018; 14: 1263-70.
Gu LP, Jin S, Xu RC, et al. Long non-coding RNA PCAT-1 promotes tumor progression by inhibiting miR-129-5p in human ovarian cancer. Arch Med Sci 2019; 15: 513-21.
Wang Y, Xu G, Chen W, et al. Detection of long-chain non-encoding RNA differential expression in non-small cell lung cancer by microarray analysis and preliminary verification. Mol Med Rep 2015; 11: 1925-32.
Balas MM, Johnson AM. Exploring the mechanisms behind long noncoding RNAs and cancer. Noncoding RNA Res 2018; 3: 108-17.
Wang ZY, Xiong J, Zhang SS, Wang JJ, Gong ZJ, Dai MH. Up-regulation of microRNA-183 promotes cell proliferation and invasion in glioma by directly targeting NEFL. Cell Mol Neurobiol 2016; 36: 1303-10.
Tanaka H, Sasayama T, Tanaka K, et al. MicroRNA-183 upregulates HIF-1alpha by targeting isocitrate dehydrogenase 2 (IDH2) in glioma cells. J Neurooncol 2013; 111: 273-83.
Fan H, Yuan R, Cheng S, Xiong K, Zhu X, Zhang Y. Overexpressed miR-183 promoted glioblastoma radioresistance via down-regulating LRIG1. Biomed Pharmacother 2018; 97: 1554-63.
Yang Z, Zhong L, Zhong S, Xian R, Yuan B. Adenovirus encoding Smad4 suppresses glioma cell proliferation and increases apoptosis through cell cycle arrest at G1 phase. Int Immunopharmacol 2015; 25: 169-73.
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