Abstract 1065: Reduced expression of microRNA-200 family associated with aggressiveness and poorer patient outcome of clear cell renal cell carcinomas

[Introduction] The aim of this study was to clarify the significance of alterations of microRNA (miRNA) expression during renal carcinogenesis. [Materials and methods] Expression profiles of miRNA were examined using the SurePrint G3 miRNA Expression microarray in paired samples of cancerous tissue (T) and non-cancerous renal cortex tissue (N) from 95 patients with clear cell renal cell carcinomas (RCCs). The expression levels of miRNA and mRNA were quantified by reverse transcription PCR (RT-PCR) using TaqMan system. The MetaCore pathway analysis by GeneGo was performed using miRNAs of which expression levels were significantly altered during renal carcinogenesis. [Results] The expression levels of 39 and 169 miRNAs were increased (T/N> = 2) and reduced (T/N −15 ). The expression levels of any of 5 EMT-related miRNAs, i.e. miR-200a, miR-200c, miR-141, miR-429 and miR-200b, called as miR-200 family, were reduced in 93 (98%) of the examined 95 RCCs. Quantitative RT-PCR analysis verified that the expression levels of miR-200 family were significantly reduced in T samples relative to the corresponding N samples. Additionally, the mRNA expression levels of the ZEB1 and ZEB2 genes, which were downstream targets of miR-200 family, were significantly increased, and their target CDH1 gene expression was further decrease in T samples. The expression levels of miR-200 family in T samples were significantly correlated with clinicopathological parameters reflecting tumor aggressiveness, such as invasive macroscopic configuration, higher histological grade, vascular involvement, renal vein tumor thrombus, invasive growth pattern, tumor necrosis, distant metastasis and higher histological TNM stage. Moreover, the expression levels of miR-200 family were significantly correlated with both of cancer-free and overall survival rates of patients with clear cell RCCs. [Conclusions] These data suggested that reduced expression of miR-200 family may participate in the malignant progression resulting in poorer patient outcome of clear cell RCCs, via regulation of the EMT pathway. Citation Format: Masahiro Gotoh, Eri Arai, Akio Matsuda, Hiroyuki Fujimoto, Kenji Matsumoto, Yae Kanai. Reduced expression of microRNA-200 family associated with aggressiveness and poorer patient outcome of clear cell renal cell carcinomas. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1065.