MicroRNA-21 contributes to renal cell carcinoma cell invasiveness and angiogenesis via the PDCD4/c-Jun (AP-1) signalling pathway

Abstract

Accumulating evidence has demonstrated that microRNAs are associated with malignant biological behaviour, including tumorigenesis, cancer progression and metastasis via the regulation of target gene expression. Our previous study demonstrated that programmed cell death protein 4 (PDCD4), which is a tumour suppressor gene, is a target of microRNA-21 (miR-21), which affects the proliferation and transformation capabilities of renal cell carcinoma (RCC) cells. However, the role of miR-21 in the molecular mechanism underlying the migration, invasion and angiogenesis of RCC remains poorly understood. The effects of miR-21 on the invasion, migration and angiogenesis of RCC cells was determined through meta-analysis and regulation of miR-21 expression in vitro. After searching several databases, 6 articles including a total of 473 patients met the eligibility criteria for this analysis. The combined results of the meta-analysis revealed that increased miR-21 expression was significantly associated with adverse prognosis in patients with RCC, with a pooled hazard ratio estimate of 1.740. In in vitro experiments, we demonstrated that a miR-21 inhibitor decreased the number of migrating and invading A498 and 786-O RCC cells, along with a decrease in PDCD4, c-Jun, matrix metalloproteinase (MMP)2 and MMP9 expression. Additionally, inhibition of miR-21 was revealed to reduce tube formation and tube junctions in the endothelial cell line HMEC-1 by affecting the expression of angiotensin-1 and vascular endothelial growth factor A, whereas PDCD4 small interfering RNA exerted opposite effects on the same cells. Overall, these findings, along with evidence-based molecular biology, demonstrated that miR-21 expression promoted the migration, invasion and angiogenic abilities of RCC cells by directly targeting the PDCD4/c-Jun signalling pathway. The results may help elucidate the molecular mechanism underlying the development and progression of RCC and provide a promising target for microRNA-based therapy.