Mevalonate pathway inhibition reduces bladder cancer metastasis by modulating RhoB protein stability and integrin β1 localization

Metastasis is an important factor affecting the prognosis and survival of bladder cancer (BLCA) patients. Our previous study found that the mevalonate pathway is associated with the migratory ability of BLCA cells, but the exact mechanism is unclear. Here, we found that BLCA patients with mevalonate pathway activation had a poorer prognosis. Inhibition of the mevalonate pathway (FDPS knockdown, simvastatin or zoledronic acid) significantly reduced the migratory ability of BLCA cells. Therefore, we tested the changes of key genes after knocking down the key enzymes of the mevalonate pathway, FDPS and SQLE1, and the transcription factor YY1 in bladder cancer cells using RNA sequencing. To investigate the roles of FDPS, SQLE and YY1 in BLCA, we first knocked down the target genes FDPS, SQLE or YY1 in the T24 BLCA cell line using the corresponding siRNAs, respectively, and all of these siRNAs were proved to have good knockdown efficiency. Then, in order to ensure the reliability of the results, we performed independent experiments three times for each sample. Finally, the 12 samples were analyzed by RNA sequencing. (N = negative control, S = siSQLE, F = siFDPS, Y = siYY1)