MiR-135a-5p and miR-124-3p Inhibit Malignancy of Glioblastoma by Downregulation of Syndecan Binding Protein.

Abstract

Due to its high invasiveness, glioblastoma is difficult to treat by surgery, radiotherapy, chemotherapy or any combination therapy. Syndecan binding protein (SDCBP), a widely distributed intracellular scaffold protein, has an important role in both physiological and pathological process. In the current work, we have identified target sequences for miR-135a-5p and miR-124-3p in the 3'-untranslated region of the SDCBP mRNA. Therefore, we have investigated the relationship between SDCBP, miR-135a-5p and miR-124-3p in glioblastoma multiforme cells T98G and U87 in vitro and in vivo. Dual luciferase activity assay documented that SDCBP is, in fact, the target of miR-135a-5p, miR-124-3. Western blot, qRT-PCR, proliferation, migration, and invasion assays have demonstrated that of silencing SDCBP or overexpressing miR-135a-5p/miR-124-3p significantly interferes with the malignant properties of glioblastoma cells. In vivo studies have shown that silencing SDCBP or overexpressing miR-135a-5p/miR-124-3p result in a marked decrease of tumor size and prolong life of tumor-bearing mice. A therapy combining the three treatments inhibits synergistically subcutaneous tumor growth in nude mice. In conclusion, proliferation, migration and invasion of glioblastoma can be inhibited by targeted regulation of SDCBP through upregulation of miR-135a-5p and miR-124-3p.