Abstract 189: miRNAs regulating members of SLC transporter family genes in penile carcinomas

Abstract

Abstract Background: Penile cancer (PeCa) is a rare disease in developed countries, but with high incidence in South America and Africa. Surgery is frequently used for local control of the disease and it can lead to partial or complete amputation of the organ, with subsequent psychosexual morbidity. Integrating data previously obtained using CGH-array and large-scale gene expression in PeCa, we found deregulation of members of solute carriage (SLCs) gene family that was not associated with genomic alterations. These findings suggested that other regulatory mechanisms could be involved, such as miRNAs. Aim: The purpose of this study was to confirm the gene expression pattern of six SLC genes (SLC1A3, SLC8A1, SLC25A4, SLC25A16, SLC25A25 and SLC27A4) and their putative regulatory miRNAs (miR-22, miR223, miR-23b, miR-26b, miR-27b and, miR-133b, respectively) in PeCa and associate the findings with clinical and pathological data. Patients and Methods: RNA was obtained from fresh PeCa (27 training and 13 validation set samples) and 4 normal penile tissues. SLC genes and miRNAs expression were evaluated by RT-qPCR. HPV genotyping was assessed using Linear Array HPV Test Genotyping (Roche). Results: Positive correlation between SLC1A3, SLC8A1, SLC25A4 and SLC27A4 expression levels detected by microarray and RT-qPCR was observed in the training set samples. Downexpression of SLC8A1 (P=0.009) and SLC25A25 (P=0.002) and overexpression of SLC27A4 (P=0.006) were detected in tumors (training and validation set) compared with normal controls, thus validating the previous findings of global gene expression. Significant downexpression of miR-23b, miR-26b, miR-27b and miR-133b and overexpression of miR-223 were detected in tumors compared with normal controls. Interestingly, lower levels of miR-133b were observed in 96% of the tumors (P=0.0007). Significant negative correlation was detected between SLC8A1 transcript levels and its putative regulatory miRNA (miR-223, P=0.015, r = −0.482) and between SLC27A4 e miR-133b (P=0.023, r = –0.454), suggesting that these genes are regulated by these miRNAs. Higher levels of SLC25A16 were found in HPV positive tumors (P=0.012). A significant association was found between lower levels of miR-23b and miR-27b and perineural invasion (P=0,032 and P=0,032; respectively). Conclusions: This study showed the deregulation of members of SLC gene family in PeCa and the involvement of putative regulatory miRNAs. miR-23b and miR-27b were found as putative prognostic markers in PeCa patients and with potential as therapeutic targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 189. doi:1538-7445.AM2012-189