Abstract
Glioma is a severe and highly lethal brain cancer, a malignancy largely stemming from growing in a relatively restrained area of the brain. Hence, the understanding of the molecular regulation of the growth of glioma is critical for improving its treatment. MicroRNA has become a hotspot in research on diseases, especially in the initiation and progression of different types of cancer. However, the molecular function and mechanisms of miR-508-5p in gliomagenesis are still unclear. The aim of this study was to investigate miR-508-5p expression in glioma and determine its effects on proliferation. miR-508-5p expression levels, both in glioma cell lines and in tissue, were significantly lower than in a normal human astrocyte cell line or adjacent tissues. Cell growth was analyzed using a MTT assay and over-expression of miR-508-5p was found to decrease glioma cell growth. Moreover, a bioinformatic analysis was performed, showing that glycoprotein non-metastatic melanoma B (GPNMB) was a direct target for miR-508-5p in glioma cells. Furthermore, in vivo treatment with miR-508-5p reduced GPNMB protein levels in the tumor. Additionally, overexpression of GPNMB without 3′-UTR partially reversed the cell growth arrest induced by miR-508-5p over-expression in glioma cells. In conclusion, these results indicate that increased expression of miR-508-5p might be related to glioma progression, indicating a potential role of miR-508-5p for clinical therapy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Watts C, Price S, Santarius T (2014) Current concepts in the surgical management of glioma patients. Clin Oncol 26:385–394
Haapasalo J, Hyartt A, Salmi M, Nordfors K, Lahtela S, Kähkönen M, Helén P, Haapasalo H (2013) Diagnosis and prognosis of gliomas–current prospects of molecular diagnostics. Duodecim Laaketieteellinen Aikakauskirja 130:893–901
Selbach M, Schwanhäusser B, Thierfelder N, Fang Z, Khanin R, Rajewsky N (2008) Widespread changes in protein synthesis induced by microRNAs. Nature 455:58–63
Wang K, Wang X, Zou J, Zhang A, Wan Y, Pu P, Song Z, Qian C, Chen Y, Yang S (2013) miR-92b controls glioma proliferation and invasion through regulating Wnt/beta-catenin signaling via Nemo-like kinase. Neuro Oncol 15:578–588
Hu X, Chen D, Cui Y, Li Z, Huang J (2013) Targeting microRNA-23a to inhibit glioma cell invasion via HOXD10. Sci Rep 3:3423
Jiang Y, Yin L, Jing H, Zhang H (2015) MicroRNA-219-5p exerts tumor suppressor function by targeting ROBO1 in glioblastoma. Tumor Bio 36(11):8943–8951
Guessous F, Alvarado-Velez M, Marcinkiewicz L, Zhang Y, Kim J, Heister S, Kefas B, Godlewski J, Schiff D, Purow B (2013) Oncogenic effects of miR-10b in glioblastoma stem cells. J Neuro Oncol 112:153–163
Huang JJ, Ma WJ, Yokoyama S (2012) Expression and immunolocalization of Gpnmb, a glioma-associated glycoprotein, in normal and inflamed central nervous systems of adult rats. Brain Behav 2:85–96
Kuan C-T, Wakiya K, Dowell JM, Herndon JE, Reardon DA, Graner MW, Riggins GJ, Wikstrand CJ, Bigner DD (2006) Glycoprotein nonmetastatic melanoma protein B, a potential molecular therapeutic target in patients with glioblastoma multiforme. Clin Cancer Res 12:1970–1982
Tyburczy ME, Kotulska K, Pokarowski P, Mieczkowski J, Kucharska J, Grajkowska W, Roszkowski M, Jozwiak S, Kaminska B (2010) Novel proteins regulated by mTOR in subependymal giant cell astrocytomas of patients with tuberous sclerosis complex and new therapeutic implications. Am J Pathol 176:1878–1890
Calin GA, Croce CM (2006) MicroRNA signatures in human cancers. Nat Rev Cancer 6:857–866
Chitwood DH, Timmermans MC (2010) Small RNAs are on the move. Nature 467:415–419
Sun J, Shi H, Lai N, Liao K, Zhang S, Lu X (2014) Overexpression of microRNA-155 predicts poor prognosis in glioma patients. Med Oncol 31:1–5
Liu C, Liang S, Xiao S, Lin Q, Chen X, Wu Y, Fu J (2015) MicroRNA-27b inhibits Spry2 expression and promotes cell invasion in glioma U251 cells. Oncol Lett 9:1393–1397
Williams MD, Esmaeli B, Soheili A, Simantov R, Gombos DS, Bedikian AY, Hwu P (2010) GPNMB expression in uveal melanoma: a potential for targeted therapy. Melanoma Res 20:184–190
Zhao Y, Qiao Z, Shan S, Sun Q, Zhang J (2012) Expression of glycoprotein non-metastatic melanoma protein B in cutaneous malignant and benign lesions: a tissue microarray study. Chin Med J 125:3279–3282
Rose AA, Grosset A-A, Dong Z, Russo C, MacDonald PA, Bertos NR, St-Pierre Y, Simantov R, Hallett M, Park M (2010) Glycoprotein nonmetastatic B is an independent prognostic indicator of recurrence and a novel therapeutic target in breast cancer. Clin Cancer Res 16:2147–2156
Weterman MA, Ajubi N, van Dinter IM, Degen WG, van Muijen GN, Ruiter DJ, Bloemers HP (1995) nmb, a novel gene, is expressed in low-metastatic human melanoma cell lines and xenografts. Int J Cancer 60:73–81
Rich JN, Shi Q, Hjelmeland M, Cummings TJ, Kuan C-T, Bigner DD, Counter CM, Wang X-F (2003) Bone-related genes expressed in advanced malignancies induce invasion and metastasis in a genetically defined human cancer model. J Biol Chem 278:15951–15957
Xiao B, Tan L, He B, Liu Z, Xu R (2013) MiRNA-329 targeting E2F1 inhibits cell proliferation in glioma cells. J Transl Med 11:204–208
Jovanovic M, Hengartner M (2006) miRNAs and apoptosis: RNAs to die for. Oncogene 25:6176–6187
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors have no conflict of interest.
Rights and permissions
About this article
Cite this article
Bao, G., Wang, N., Li, R. et al. MiR-508-5p Inhibits the Progression of Glioma by Targeting Glycoprotein Non-metastatic Melanoma B. Neurochem Res 41, 1684–1690 (2016). https://doi.org/10.1007/s11064-016-1884-2
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11064-016-1884-2