MicroRNA-186 targets IGF-1R and exerts tumor-suppressing functions in glioma

Abstract

Glioma is the most common malignant brain tumor in adults and represents one of the most aggressive and life‑threatening types of cancer in humans. Increasing studies have revealed that microRNAs are abnormally expressed in various types of human cancer, and have oncogenic or tumor suppressive roles, which depend primarily on the type of cancer. The present study aimed to investigate the expression level and effects of microRNA‑186 (miR‑186) on glioma, and its underlying molecular mechanism. Reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR) analysis was performed to detect the expression of miR‑186 in glioma tissues and cell lines. Cell proliferation and invasion were assessed using MTT and cell invasion assays, respectively. Bioinformatics analysis and a luciferase reporter assay were performed to identify insulin‑like growth factor 1 receptor (IGF‑1R) as a novel target gene of miR‑186. The mRNA expression level of IGF‑1R was also measured using RT‑qPCR analysis. The association between miR‑186 and the expression of IGF‑1R was evaluated using Spearman's correlation anal-ysis. Furthermore, the regulatory effects of miR‑186 on the mRNA and protein expression of IGF‑1R were determined using RT‑qPCR and western blot analyses. Finally, the biological effects of the underexpression IGF‑1R on glioma cells were investigated. The results showed that miR‑186 was significantly downregulated in glioma tissues and cell lines. Inducing the expression of miR‑186 suppressed glioma cell proliferation and invasion. IGF‑1R was confirmed as a direct target gene of miR‑186. In addition, the mRNA expression of IGF‑1R was upregulated and inversely correlated with that of miR‑186 in glioma tissues. The effects of IGF‑1R‑knockdown on glioma cell proliferation and invasion were similar to the effects induced by the overexpression of miR‑186. These findings demonstrated that miR‑186 acted as a tumor suppressor by targeting IGF‑1R in glioma, suggesting miR‑186 may be a potential therapeutic target for the treatment of this disease.

lncRNA SNHG11 facilitates prostate cancer progression through the upregulation of IGF‑1R expression and by sponging miR‑184

“…IGF-1R overexpression reversed the suppressive effects induced by SNHG11 knockdown on the malignant phenotypes of PCa cells. Previous studies have also demonstrated that IGF-1R plays an oncogenic role in several types of cancer, including PCa ( 28 ), bladder cancer ( 29 ), colorectal cancer ( 26 ) and glioma ( 30 ). Similarly, the data of the present study also suggested that IGF-1R may act as an oncogene in PCa.…”

BAG2 Promotes Proliferation and Metastasis of Gastric Cancer via ERK1/2 Signaling and Partially Regulated by miR186

“…Thus, miRNAs play a vital role in tumorigenesis, biological development, organogenesis, apparent regulation, and metabolism (27,28). Previous studies have shown that miR186 targeted IGF-1R in glioma (29), and Yin Yang 1 (YY1) and cyclin dependent kinase 6 (CDK6) in prostate cancer (30). In addition, PTTG1 (31), P2X7 (32), FOXO1 (33), AKAP12 (34,35) and Caspase-10 (36) have also been identified as direct targets of miR186 in different types of cancer in recent years.…”

Receptor tyrosine kinase expression in high‑grade gliomas before and after chemoradiotherapy

“…A number of studies focused on IGF1R have identified that IGF1R expression is associated with numerous types of tumors, including glioma (26–29). IGF-1R has also been confirmed as a direct target gene of numerous microRNAs that are associated with glioma proliferation and invasion (27,30). The IGF1R pathway has been reported to be associated with treatment resistance in glioma (29).…”