LINC01638 lncRNA mediates the postoperative distant recurrence of bladder cancer by upregulating ROCK2

It is well established that long intergenic non-protein coding RNA 1638 (LINC01638) promotes the development and progression of breast cancer, whereas its roles in other human diseases are currently unknown. In the present study, expression of LINC01638 and ROCK2 was analyzed using quantitative PCR, ELISA and western blot. Receiver operating characteristic curve was used for diagnostic analysis. Cell transfections were performed to analyze interactions between LINC01638 and ROCK2, while Transwell assays were performed to analyze invasion and migration of the bladder cancer HT-1197 and HT-1376 cell lines. It was observed that LINC01638 and Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) were significantly upregulated in the plasma of patients with early stage (stage I and II) bladder cancer compared with in healthy controls. Upregulation of LINC01638 and ROCK2 distinguished patients with early stage bladder cancer from healthy controls. Plasma levels of LINC01638 and ROCK2 were positively correlated in patients with bladder cancer, but not in healthy controls. A follow-up study after surgical resection revealed that LINC01638 and ROCK2 were further upregulated in patients with distant recurrence, or distant and local recurrence, but not in patients with local recurrence and no recurrence. Overexpression of LINC01638 led to ROCK2 upregulation in bladder cancer cells, whereas ROCK2 overexpression did not significantly affect LINC01638 expression. Overexpression of LINC01638 and ROCK2 mediated the promoted migration and invasion of bladder cancer cells, and ROCK2 small interfering RNA silencing attenuated the enhancing effects of LINC01638 on cancer cell migration and invasion. Therefore, LINC01638 may mediate the postoperative distant recurrence of bladder cancer by upregulating ROCK2.