MicroRNAs in Renal Cell Carcinoma: Diagnostic Implications of Serum miR-1233 Levels

Abstract

BackgroundMicroRNA expression is altered in cancer cells, and microRNAs could serve as diagnostic/prognostic biomarker for cancer patients. Our study was designed to analyze circulating serum microRNAs in patients with renal cell carcinoma (RCC).Methodology/Principal FindingsWe first explored microRNA expression profiles in tissue and serum using TaqMan Low Density Arrays in each six malignant and benign samples: Although 109 microRNAs were circulating at higher levels in cancer patients' serum, we identified only 36 microRNAs with up-regulation in RCC tissue and serum of RCC patients. Seven candidate microRNAs were selected for verification based on the finding of up-regulation in serum and tissue of RCC patients: miR-7-1*, miR-93, miR-106b*, miR-210, miR-320b, miR-1233 and miR-1290 levels in serum of healthy controls (n = 30) and RCC (n = 33) patients were determined using quantitative real-time PCR (TaqMan MicroRNA Assays). miR-1233 was increased in RCC patients, and thus validated in a multicentre cohort of 84 RCC patients and 93 healthy controls using quantitative real-time PCR (sensitivity 77.4%, specificity 37.6%, AUC 0.588). We also studied 13 samples of patients with angiomyolipoma or oncocytoma, whose serum miR-1233 levels were similar to RCC patients. Circulating microRNAs were not correlated with clinical-pathological parameters.Conclusions/SignificanceMicroRNA levels are distinctly increased in cancer patients, although only a small subset of circulating microRNAs has a tumor-specific origin. We identify circulating miR-1233 as a potential biomarker for RCC patients. Larger-scaled studies are warranted to fully explore the role of circulating microRNAs in RCC.

Profiling analysis of circulating microRNA expression in cervical cancer

“…It has been reported that 6 miRNAs, including miR-1290, are upregulated in drug-sensitive cells following Y-Box protein 1 inhibition, but no differences in miRNA expression have been detected in multidrug-resistant gastric carcinoma cells (23). It has also been reported that 36 miRNAs, including miR-1290, circulate at higher levels in subjects with renal cell carcinoma compared with those in healthy controls (24).…”

Human mirtrons can express functional microRNAs simultaneously from both arms in a flanking exon-independent manner

“…In spite of its unusual features, mir-1233 miRNA was claimed to have medical relevance in certain leukemia samples 31 and as a biomarker for renal cell carcinoma. 32 In another study, potential function for mir-1226 as a canonical miRNA in tumor suppression was also described. 33 Our study confirmed that mir-877 and mir-1226 are typical mirtrons and showed that they function properly when expressed either from their endogenous or from a heterologous coding context.…”

Downregulation of miR-544 in tissue, but not in serum, is a novel biomarker of malignant transformation in glioma

“…However, a different correlation between circulating miRNAs and tissue miRNAs has also been observed. Wulfken et al observed 109 miRNAs at higher levels in the serum of patients with renal cell carcinoma, but only 36 miRNAs were upregulated in tissue samples (27). Another study reported that approximately 66% of the released miRNAs reflect the cellular miRNA content of malignant mammary epithelial cells (28).…”