MiR-26b suppresses cell proliferation and invasion by targeting cyclooxygenase 2 in human glioblastoma

Qiyong Jiang,Shijuan Zhang,Naikun Li,Yimin Liu,Gaoling Sun

doi:10.18632/oncotarget.12706

Abstract

// Qiyong Jiang 1, * , Yimin Liu 2, * , Shijuan Zhang 3 , Naikun Li 2 , Gaoling Sun 1 1 Department of Neurosurgery, Yidu Central Hospital, Weifang Medical University, Qingzhou 262500, Shandong, P.R. China 2 Department of Neurology, Yidu Central Hospital, Weifang Medical University, Qingzhou 262500, Shandong, P.R. China 3 Department of Intensive Care Unit, Yidu Central Hospital, Weifang Medical University, Qingzhou 262500, Shandong, P.R. China * These authors have contributed equally to this work as the co-first author Correspondence to: Qiyong Jiang, email: jiangqiyongwfyidu@163.com Keywords: miR-26b, COX-2, GBM Received: August 29, 2016      Accepted: October 05, 2016      Published: October 17, 2016 ABSTRACT MiRNAs are emerging as important epigenetic modulators of multiple target genes, leading to abnormal cellular signaling involving cellular proliferation in cancers. Aberrant miRNA expression has been observed in human glioblastoma (GBM). The present study was to evaluate the expression and molecular mechanisms of COX-2 and miR-26b in human GBM tissues and GBM cell lines T98G, U87 and U251. In the present study, we found that expression of miR-26b was markedly downregulated in GBM cell lines and human GBM tissues, compared to matched non-tumor associated tissues. Furthermore, miR-26b expression was inversely proportional to that of COX-2 mRNA and protein. Ectopic expression of miR-26b dramatically reduced the proliferation, colony formation, and proliferation/apoptosis-related proteins in GBM cells. Flow cytometry analysis showed that ectopic expression of miR-26b significantly decreased the percentage of S phase cells and increased the percentage of G1/G0 phase cells. Finally, luciferase reporter assay revealed that miR-26b inhibited the expression of COX-2 by binding to the 3'-UTR of COX-2 in GBM cells. Taken together, our results suggest that miR-26b plays an important role to inhibit the proliferation and invasion of GBM cells, and presents a novel mechanism for direct miR-26b-mediated suppression of COX-2 in GBM. Thus, miR-26b/COX-2 may have an important role in treatment of GBM patients.

Highlights

Gliomas have been reported as the most common one of primary cerebral tumors in central neural system
Our findings showed that the expression of COX-2 mRNA was significantly up-regulated in cancer tissues, the expression was not changed in their own adjacent non-tumor tissues (p
Our findings showed that the expression of COX-2 mRNA and protein were obviously higher as compared with their own adjacent non-tumor tissues (Figure 2a, 2b)

Summary

Introduction

Gliomas have been reported as the most common one of primary cerebral tumors in central neural system. The glioblastoma multiforme (GBM) acts as grade IV glioma, and has the most common and malignant properties [5,6]. Due to the unsatisfactory survival status of patients with GBM, it is essential to hunt for some new and useful biomarker, which can be applied into diagnosis and treatment. The miRNA-induced potential regulation mechanisms are still under investigation, some current reports have indicated that the expression model of miRNA will be useful for the diagnosis and prognosis of www.impactjournals.com/oncotarget human tumors. It has been reported that miR-26b has a wide role in regulation of some functions involving suppression of cancer cell proliferation and inhibition of organ metastasis of different cancers. Little is known about the role of miR-26b in the development of GBM

Methods

Results

Conclusion