Abstract 4934: Up-regulation of microRNA-21 correlates with lower survival of kidney cancer

MicroRNA-21 is up-regulated in a variety of cancers, such as breast, colorectal, lung, head and neck, etc. However, the regulation of miR-21 in kidney cancer has not yet been studied systematically. We measured miR-21 levels in 40 pairs of kidney cancers and their normal matched tissues by real-time PCR. In 36 cases (90%), miR-21 was increased (ratios of miR-21 levels in tumors to normal tissues T/N were greater than 1.5). The expression level of miR-21 was correlated with 5 year survival and the stage of the patients. For patients with low miR-21 expression, all survived 5 years after the operation, while in case of high miR-21 expression, only 59% survived. In groups of patients having low expression (T/N 10), the percent of early stage (Stage I) decreased: 100%, 76% and 43%, respectively. To study the biological effect of miR-21 up-regulation, a kidney cancer cell line A498 was transfected with miR-21 anti-miRNA inhibitor. The miR-21 level was reduced by more than 99%, as compared to the negative control. Flow cytometry analysis of the cell cycle showed a significant increase in G0/G1 phase (9.1%), with a concomitant reduction in the G2/M phase (6.8%), indicating that the forced reduction of miR-21 expression in A498 cells could inhibit the cell growth and cause G0/G1 arrest. Apoptosis assay using flow cytometry showed a significant increase in the number of total apoptotic cells in the miR-21 anti-miRNA inhibitor transfected cells as compared to the negative control. MiR-21 gene was mapped to chromosome 17q23, and increased copy numbers of this section, which includes oncogenes like erb-B2/HER-2, RPS6KB1, etc., were frequently present in cancers. We compared the miR-21 expression levels with the amplification of this section in 30 cancer cell lines, including 5 kidney cancer, 6 breast cancer, 15 colorectal cancer, 3 prostate cancer, and 1 bladder cancer. We observed a significant correlation between the amplification of 17q and high miR-21 expression. In conclusion, the up-regulated miR-21 in kidney cancer could be used as a tumor marker for diagnosis. The inhibition of miR-21 and/or its adjacent oncogenic genes may prove to be useful in controlling cancers with up-regulated miR-21. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 4934. doi:10.1158/1538-7445.AM2011-4934