Shaanxi Center for Clinical Laboratory, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
Shaanxi Key Laboratory of Ischemic Cardiovascular Disease, Shaanxi Key Laboratory of Brain Disorders, Institute of Basic & Translational Medicine, Xi'an Medical University, Xi'an 710021, China.
Chem Biol Interact. 2021 Mar 1;337:109366. doi: 10.1016/j.cbi.2021.109366. Epub 2021 Feb 4.
Tripartite motif-containing protein 26 (TRIM26) is a member of the TRIM protein family and has been demonstrated to play crucial roles in several types of cancers. However, the biological role of TRIM26 in bladder cancer and the mechanism have not been studied. In this study, we investigated the expression of TRIM26 in bladder cancer tissues and their adjacent non-tumor tissues by Western blot and qRT-PCR. In vitro investigations were performed to assess the roles of TRIM26 in bladder cancer using TRIM26-silencing and TRIM26-overexpressing bladder cancer cell lines. MTT and EdU assays were performed to evaluate cell proliferation. Cell migration and invasion were determined by transwell assays. Western blot analysis was performed to detect the expression levels of p-Akt, Akt, p-GSK3β, GSK3β, β-catenin and c-Myc. Our results showed that TRIM26 expression was upregulated in human bladder cancer tissues and cell lines at both mRNA and protein levels. Knockdown of TRIM26 significantly inhibited the proliferation, migration and invasion of bladder cancer cells. In contrast, TRIM26 overexpression promoted bladder cancer cell proliferation, cell migration and invasion. Furthermore, knockdown of TRIM26 significantly decreased the levels of p-Akt, p-GSK3β, β-catenin and c-Myc in bladder cancer cells. Additionally, induction of Akt by SC79 treatment reversed the inhibitory effects of TRIM26 knockdown on the cellular behaviors of bladder cancer cells, while inhibition of β-catenin reversed the effects of TRIM26 overexpression on the behaviors. Finally, knockdown of TRIM26 attenuated the growth of tumor xenografts in nude mice. In conclusion, these findings demonstrated that TRIM26 exerted an oncogenic role in bladder cancer through regulation of cell proliferation, migration and invasion via the Akt/GSK3β/β-catenin pathway.
三结构域蛋白 26（TRIM26）是 TRIM 蛋白家族的一员，已被证明在多种类型的癌症中发挥关键作用。然而，TRIM26 在膀胱癌中的生物学作用及其机制尚未得到研究。在这项研究中，我们通过 Western blot 和 qRT-PCR 检测了膀胱癌组织及其相邻非肿瘤组织中 TRIM26 的表达。通过沉默和过表达 TRIM26 的膀胱癌细胞系进行体外研究，以评估 TRIM26 在膀胱癌中的作用。MTT 和 EdU 测定用于评估细胞增殖。通过 Transwell 测定评估细胞迁移和侵袭。Western blot 分析用于检测 p-Akt、Akt、p-GSK3β、GSK3β、β-catenin 和 c-Myc 的表达水平。我们的结果表明，TRIM26 在人膀胱癌组织和细胞系中均在 mRNA 和蛋白水平上上调。沉默 TRIM26 显著抑制膀胱癌细胞的增殖、迁移和侵袭。相反，过表达 TRIM26 促进膀胱癌细胞增殖、细胞迁移和侵袭。此外，沉默 TRIM26 显著降低了膀胱癌细胞中 p-Akt、p-GSK3β、β-catenin 和 c-Myc 的水平。此外，用 SC79 处理诱导 Akt 逆转了 TRIM26 沉默对膀胱癌细胞细胞行为的抑制作用，而抑制 β-catenin 逆转了 TRIM26 过表达对行为的作用。最后，沉默 TRIM26 减弱了裸鼠肿瘤异种移植的生长。总之，这些发现表明，TRIM26 通过调节 Akt/GSK3β/β-catenin 通路调节细胞增殖、迁移和侵袭，在膀胱癌中发挥致癌作用。
