Monocarboxylate transporter 9 (MCT9) is down-regulated in renal cell carcinoma.

Abstract

The renal cell carcinoma (RCC) incidences are continuously increasing, however, their proper characterization remains difficult. Mammalian kidneys require large amounts of energy, and monocarboxylate transporter (MCT) gene family is responsible for the transport of monocarboxylic compounds across plasma membranes. A total of 14 MCT members have been identified in humans, which show highly distinct substrate affinities and tissue distributions. To understand the yet-uncharacterized renal cancer-specific role of MCTs, we identified MCT members that are differentially regulated during the renal tumor progression. We examined the expression level of MCT members in renal cell tumors and their relationship with survival rate of patients using a public database. Quantitative RT-PCR and northern blotting were performed to validate the expression of MCTs. Anti-MCT9 antiserum was raised in rabbit and used to examine MCT9 expression in normal and tumor tissue arrays. Effect of MCT9 overexpression on cell proliferation was measured using renal cancer cell lines. MCT9 was found to be abundantly and exclusively expressed in human kidney cells, and was highly downregulated in renal cancers. Kaplan-Meier plotter analysis revealed an increased survival rate of MCT9 high-expressing RCC patients. MCT9 proteins were detected in normal kidney tissue sections and their overexpression clearly attenuated renal cell proliferation. MCT9 was identified as a novel highly downregulated gene in renal cell cancer, and its overexpression clearly attenuated RCC cell proliferation. Thus, functional analysis of MCT9 may help in deciphering a yet-undiscovered kidney-specific energy metabolism during renal tumor progression.