MicroRNA-182 suppresses clear cell renal cell carcinoma migration and invasion by targeting IGF1R

Abstract

The purpose of our study was aimed to determine the functional role of microRNA (miR)-182 in clear cell renal cell carcinoma (ccRCC) and try to clarify its underlying molecular mechanism. Expression of miR-182 in both cancer and peripheral blood samples was analyzed by quantitative real-time PCR (qRT-PCR). Human RCC line Caki-1 cells were transfected with miR-182 mimic, miR-182 inhibitor, or negative controls, and then the cell viability, colony-formation ability, migration, and invasion assay were determined. Luciferase reporter assay, qRT-PCR and Western blotting were used to determine whether insulin-like growth factor 1 receptor (IGF1R) was a target of miR-182. Further, small interfering RNA (siRNA) against IGF1R was co-transfected with miR-182 inhibitor into cells, and then the effects on migration and invasion were assessed. MiR-182 was down-regulated in both cancer and blood samples compared to the matched non-tumor adjacent tissues and healthy volunteers, respectively (both P<0.05). Compared to the control group, cell viability, colony-forming ability, and numbers of migrated and invaded cells were significantly decreased by transfection with miR-182 mimic but were markedly increased by miR-182 inhibitor (all P < 0.05). Luciferase reporter assay confirmed that IGF1R was a target gene of miR-182, and IGF1R was negatively regulated by miR-182. Co-transfection of miR-182 inhibitor with si-IGF1R reversed the effect of miR-182 inhibitor on the migration and invasion of the cells. MiR-182 functions as an anti-oncogene in ccRCC, and miR-182-mediated inhibition of cell migration and invasion might be through directly targeting IGF1R. Key words: MicroRNA-182, clear cell renal cell carcinoma, migration and invasion, insulin-like growth factor 1 receptorRenal cell carcinoma (RCC) is the most common malignant tumor of adult kidney and accounts for approximately 3% of adult cancers with a high mortality at over 40% [1,2]. Clear cell renal cell carcinoma (ccRCC) is the most frequent subtype of RCC accounting for about 75-80% of the tumor [3]. Despite a tremendous advance has been made in available treatments, the prognosis still remains dismal for locally advanced and metastatic RCC [4]. It has been reported that up to 30-40% of patients with RCC present with metastatic disease even after radical resections [5]. Therefore, it is necessary to provide knowledge of molecule mechanisms controlling the metastatic and invasive potential of RCC.MicroRNAs (miRNAs) are a class of small and non-coding RNA molecules that regulate mRNA transcription and translation by base pairing with the 3' untranslated region (UTR) [6]. It has been well demonstrated that miRNAs are involved in the development and progression of various cancers by regulating cell proliferation, invasion, and migration [7,8]. Recently, emerging evidence has suggested the significant roles of miRNAs in RCC [9][10][11]. Among miRNAs, miR-182 was recently found to be associated with the invasive and/or metastatic potential of prostate cancer [12], melanoma [13], an...

miR-182-5p promotes hepatocellular carcinoma progression by repressing FOXO3a

“…However, the function of miR-182-5p is complicated because it can be an oncogene or a tumor suppressor in the context of different cancers. miR-182-5p is identified as onco-miR in ovarian cancer [ 6 ], breast cancer [ 7 ], and melanoma [ 8 ] and acts as tumor suppressor in RCC [ 9 , 10 ] and glioblastoma [ 11 , 12 ]. In HCC, miR-182-5p contributes to HCC metastasis by targeting metastasis suppressor 1 (MTSS1) [ 13 ], and upregulated miR-182-5p increases drug resistance in cisplatin-treated HCC cells by regulating tumor protein 53-induced nuclear protein 1 (TP53INP1) [ 14 ].…”

MiR‐182 inhibits the epithelial to mesenchymal transition and metastasis of lung cancer cells by targeting the Met gene

“…Recently, a study by Wang et al revealed that IGF1R, another tyrosine kinase receptor, is a direct target gene of miR‐182, and miR‐182 suppresses the migration and invasion in clear cell renal cell carcinoma . Based on our findings that miR‐182 suppressed HGF‐induced phosphorylation of AKT, we inquired whether miR‐182 also suppressed IGF‐induced phosphorylation of AKT and suppressed the tumor cell EMT process.…”

“…D, A549 cells were transfected with miR-182 or control scrambled oligonucleotides and then treated with HGF for different time periods (0 h, 15 min, 30 min, 1 h, 2 h, and 12 h), and the expressional change in E-cadherin was measured in these cells by Western blotting analysis. E, A549 cells were transfected with miR-182 or Met siRNA or a combination of control miR-182 and Met siRNA or scrambled oligonucleotides and then stimulated with or without HGF for 2 h. The expressional change in E-cadherin was measured in these cells by fluorescent immunocytochemical analysis carcinoma 28. Based on our findings that miR-182 suppressed HGFinduced phosphorylation of AKT, we inquired whether miR-182 also suppressed IGF-induced phosphorylation of AKT and suppressed the tumor cell EMT process.…”

Integrated analysis of a competing endogenous RNA network in renal cell carcinoma using bioinformatics tools

“…In the present study, we identified 17 DEmiRNAs in the ceRNA network. Among them, several miRNAs have been reported to play important roles in the initiation and development of RCC, such as miR-182, miR-136, and miR-629 [31][32][33]. To further identify the key circRNAs participating in the regulatory network, we established the PPI network, thereby screening 8 hub genes.…”