MicroRNA.15b.5p exerts its tumor repressive role via targeting GDI2: A novel insight into the pathogenesis of thyroid carcinoma

Abstract

Thyroid carcinoma (THCA ) is a malignant tumor of the endocrine system. Previous studies have revealed the vital roles of microRNA s (miRNA s/miRs) in THCA procession. The present study aimed to explore the effects of miR. 15b.5p on the progression of THCA and its targeting mechanism. The data of THCA and healthy samples were firstly collected from starbase2.0 and used to analyze the relationship of miR. 15b.5p with THCA . Dual.luciferase assay was performed to detect the direct interaction between miR. 15b.5p and the predicted target gene GDP dissociation inhibitor 2 (GDI 2). The effects of miR. 15b.5p and GDI 2 on the overall survival of patients with THCA were analyzed using Kaplan.Meier analysis with log rank test. Cell Counting Kit.8 and Transwell assays were conducted to assess the impacts of miR. 15b.5p and GDI 2 on the proliferation and invasion of THCA cells. Reverse transcription.quantitative PCR and western blot analyses were performed to analyze the expression levels of the related miRNA s and proteins, respectively. miR. 15b.5p was found to be downregulated both in THCA tissues and cells, and the low expression of miR. 15b.5p was associated with the short overall survival time of patients. Moreover, the upregulation or downregulation of miR. 15b.5p could inhibit or enhance the proliferation and invasion of THCA cells, respectively. miR. 15b.5p reduced the protein expression levels of matrix metalloproteinase (MMP)2 and MMP9, which were related to cell invasion. Furthermore, GDI 2, which was enhanced in THCA and related to the poor prognosis of patients with THCA, was identified as the target gene of miR.15b.5p and negatively regulated by miR. 15b.5p. Additional experiments demonstrated that GDI2 overexpression could significantly reduce the antitumor effect of miR. 15b.5p and its inhibitory action on the expression levels of MMP2 and MMP9. Thus, the results indicated a potential tumor suppressive role of miR. 15b.5p in THCA , which was mainly exerted by targeting GDI2 and modulating MMP2 and MMP9. These findings will increase the understanding on the pathogenesis of THCA and provide novel candidates for THCA therapy.