miR-218 inhibits the tumorgenesis and proliferation of glioma cells by targeting Robo1

Article type: Research Article

Authors: Gu, Jian-Jun^{a; b; *} | Gao, Guang-Zhong^b | Zhang, Shi-Ming^c

Affiliations: [a] Department of Neurosurgery, Fuzhou General Hospital, Xiamen University Medical College, Fuzhou, Fujian, China | [b] Departments of Neurosurgery, Taizhou People's Hospital Affiliated to Medical College of The Nantong University, Taizhou, Jiangsu, China | [c] Department of Neurosurgery, The First Affiliated Hospital of Soochow University, Suzhou, China

Correspondence: [*] Corresponding author: Jian-Jun Gu, 399 Hailing South Road, Taizhou, 225300 Jiangsu, China. E-mail:[email protected]

Abstract: BACKGROUND: Malignant glioma is the most common primary brain tumors directly correlated with the high mortality and poor prognosis in clinical practice. MicroRNAs (miRNAs or miRs) influence numerous cancer-relevant processes including cell proliferation, differentiation and metabolism. However, the role of microRNA in malignant glioma is largely unknown. This study aimed to study the role of miR-218, a tumor-suppressive microRNA, in glioma development both in vivo and in vitro. METHODS: The expression level of miR-218, Slit2 and Robo1 was examined by either quantitative (polymerase chain reaction) or western-blotting from both human glioma tissue and glioma cell lines. U87 cells were transfected with miR-218 and then the expression levels of Slit2 and Robo1 were quantified. Cell proliferation was measured both by the in vitro proliferation assay and in vivo graft studies. The luciferase reporter assay was employed to validate the downstream target of miR-218. RESULTS: The expression of miR-218 was lower in glioma cell lines and glioma tissues from the patients with decreased Slit2 and increased Robo1 protein levels. The over-expression of miR-218 inhibited the tumorgenesis and proliferation of glioma cells remarkably. Furthermore, the over-expressing miR-218 in glioma cells results in the downregulation of Robo1 and upregulation of Slit2. Using luciferase reporter assays, we found that Robo1 was a direct downstream target of miR-218. CONCLUSION: Over-expression of miR-218 in glioma cells may inhibit the proliferation and tumorigenicity through targeting Robo1, suggesting that miR-218 could be a potential target for developing therapies in treating glioma.

Keywords: miR-218, gliomas, proliferation, tumorgenesis, Slit2, Robo1

DOI: 10.3233/CBM-160568

Journal: Cancer Biomarkers, vol. 16, no. 3, pp. 309-317, 2016