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 micrornas (mirnas/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 (Gdi2). The effects of mir-15b-5p and Gdi2 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 Gdi2 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 mirnas 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, Gdi2, 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.

Silencing GDI2 inhibits proliferation, migration and invasion of colorectal cancer through activation of p53 signaling pathway

“…Knockdown of GDI2 inhibits cell proliferation but promotes apoptosis(8). In thyroid cancer cells, microRNA-15b-5p can inhibit cell proliferation and invasion by targeting GDI2, which is associated with poor prognosis in thyroid cancer patients and is negatively regulated by miR-15b-5p (22). The differential expression of GDI2 in gastric cancer tissues could provide potential insights into the identi cation of biomarkers of gastric cancer biology and tumour progression (9).…”

Chemoprotective effect of boeravinone B against 1,2-dimethyl hydrazine induced colorectal cancer in rats via suppression of oxidative stress and inflammatory reaction

“…Previous reports show the expression of GDI2 is boosted in esophageal squamous cell carcinoma (37) and pancreatic cancer (38), suggesting it should be considered as a biomarker or potential molecular target for these cancers (15). A reduced expression of GDI2 is also observed in CRC, and it should be considered as a potential target for the treatment of this disease.…”

“…GDI2 is a GDP dissociation inhibitor 2 which belongs to the small family of chaperone proteins and shows a significant signal transduction molecule which regulates the expansion of various types of cancers including that of the prostate, breast, and thyroid, as well as CRC (12). Various research suggests GDI2 is heavily involved in the regulation of several biological functions including apoptosis, tumor cell proliferation, and cell metabolism and migration (13)(14)(15). Therefore, while the function of GDI2 has been previously explored in various types of the cancer, its role has not been explored in the colorectal cancer.…”