Department of Urology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai 200072, P.R. China.
Oncol Rep. 2017 Nov;38(5):2935-2940. doi: 10.3892/or.2017.5959. Epub 2017 Sep 18.
The leucine zipper-EF-hand containing transmembrane protein 1 (LETM1) is highly expressed in many human malignancies and is correlated with poor prognosis. However, the function of LETM1 in bladder cancer still remains unknown. In the present study, we analyzed the expression levels of LETM1 in bladder cancer tissues and non-cancerous tissues as well as in four bladder cancer cell lines (T24, EJ, 5637 and J82) and a human bladder epithelial immortalized cell line SV-HUC-1. Small interfering RNA (siRNA) was employed to knockdown the expression of LETM1 in the T24 cells. The proliferation of T24 cells was significantly repressed as evaluated by CCK-8 assays. Transwell migration and invasion assays indicated that knockdown of LETM1 suppressed cell migration and invasion significantly. Flow cytometric analysis revealed that cells had accumulated at the S-phase when the expression of LETM1 was suppressed. Moreover, we found that several oncogenic proteins in the Wnt/β-catenin signaling pathway, namely β-catenin, cyclin D1 and c-Myc were significantly decreased by the LETM1 siRNA. Collectively, these results revealed that the knockdown of LETM1 exhibited tumor suppressive effects, possibly by controlling the downstream Wnt/β-catenin signaling pathway.
亮氨酸拉链-EF 手跨膜蛋白 1（LETM1）在许多人类恶性肿瘤中高度表达，与预后不良相关。然而，LETM1 在膀胱癌中的功能仍然未知。在本研究中，我们分析了 LETM1 在膀胱癌组织和非癌组织以及四种膀胱癌细胞系（T24、EJ、5637 和 J82）和人膀胱上皮永生化细胞系 SV-HUC-1 中的表达水平。采用小干扰 RNA（siRNA）敲低 T24 细胞中 LETM1 的表达。通过 CCK-8 测定评估，T24 细胞的增殖明显受到抑制。Transwell 迁移和侵袭实验表明，敲低 LETM1 显著抑制细胞迁移和侵袭。流式细胞术分析显示，当 LETM1 的表达受到抑制时，细胞在 S 期积累。此外，我们发现 Wnt/β-catenin 信号通路中的几种致癌蛋白，即β-catenin、cyclin D1 和 c-Myc，被 LETM1 siRNA 显著下调。总之，这些结果表明，敲低 LETM1 表现出肿瘤抑制作用，可能通过控制下游的 Wnt/β-catenin 信号通路。
