Inhibition of LDHA Deliver Potential Anticancer Performance in Renal Cell Carcinoma

Lactate dehydrogenase A (LDHA), which functions as a crucial enzyme in transforming from pyruvate into lactate, has been reported to be overexpressed in various advanced cancer and its silencing has turned out to be tumor suppressive. Previous studies have showed that the expression of LDHA was higher in renal cell carcinoma (RCC) than that in corresponding normal renal tissue. However, the function of LDHA in RCC, and its possible mechanism in tumor progression, has not been investigated.

MTT and cell cycle assay were performed to explore the growth of the renal cells. Transwell assay for the migration and invasion and tube formation were conducted to detect the metastatic properties of the renal cancer.

Here, we show that siRNA-mediated knockdown of LDHA inhibits cell proliferation by decreasing cell cycle and promoting apoptosis in renal cancer cell lines. Mechanistically, LDHA siRNA treatment altered the expression of cell cycle- and apoptosis-related proteins, including p21, cyclin D1, Bcl-2 and Bax. In addition, LDHA siRNA treatment leads to markedly diminished migratory and invasive ability by reducing the expression of matrix metalloproteinase (MMP)-2 and MMP-9.

These findings are consistent with the view that LDHA, as an oncogene, might be a potential therapeutic target in RCC.