Department of Emergency, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
Department of Emergency Surgery, The Affiliated Huaian No.1 People's Hospital of Nanjing Medical University, Huai'an, China.
Kaohsiung J Med Sci. 2020 Jun;36(6):417-422. doi: 10.1002/kjm2.12194. Epub 2020 Feb 12.
It has been reported that tripartite motif containing 26 (TRIM26) is involved in the tumorigenesis of some cancers, but its function in non-small cell lung cancer (NSCLC) is still unclear. In this study, we found that TRIM26 was markedly down-regulated in both of NSCLC tumor tissues and cell lines. Additionally, high expression of TRIM26 in NSCLC patients predicted a positive index for patients' overall survival. What is more, overexpression of TRIM26 significantly suppressed NSCLC cell growth. Our further studies indicated that overexpression of TRIM26 inhibited the phosphorylation of PI3K p85 and AKT. And overexpressed TRIM26 regulated cell cycle-related genes' expression, including downregulating CDK4, Cyclin A, Cyclin D1, Cyclin D3, and Cyclin E, and upregulating p27 expression. Finally, we found that TRIM26 up-regulated PTEN expression by stabilizing PTEN protein in NSCLC cells. Collectively, our present study indicated that TRIM26 was decreased in NSCLC and overexpression of TRIM26 inhibited NSCLC cell growth by suppressing PI3K/AKT pathway, which suggested that TRIM26 could be as a potential target for the treatment of NSCLC in the future.
据报道,三结构域蛋白 26(TRIM26)参与了一些癌症的肿瘤发生,但它在非小细胞肺癌(NSCLC)中的作用尚不清楚。在这项研究中,我们发现在 NSCLC 肿瘤组织和细胞系中 TRIM26 的表达明显下调。此外,TRIM26 在 NSCLC 患者中的高表达预示着患者总生存率的阳性指数。更重要的是,TRIM26 的过表达显著抑制了 NSCLC 细胞的生长。我们的进一步研究表明,TRIM26 的过表达抑制了 PI3K p85 和 AKT 的磷酸化。并且过表达的 TRIM26 调节细胞周期相关基因的表达,包括下调 CDK4、Cyclin A、Cyclin D1、Cyclin D3 和 Cyclin E,以及上调 p27 的表达。最后,我们发现 TRIM26 通过稳定 NSCLC 细胞中的 PTEN 蛋白来上调 PTEN 表达。总之,我们的研究表明,TRIM26 在 NSCLC 中表达降低,TRIM26 的过表达通过抑制 PI3K/AKT 通路抑制 NSCLC 细胞的生长,这表明 TRIM26 可能成为未来治疗 NSCLC 的潜在靶点。