Department of Clinical Laboratory, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, China.
J Cell Biochem. 2019 Apr;120(4):5232-5243. doi: 10.1002/jcb.27798. Epub 2018 Oct 30.
TRIM32 is a member of the tripartite motif (TRIM) family, which has been associated with tumorigenesis. However, its expression and potential functional role(s) in lung cancer progression have not been fully understood. To evaluate the relationship between the expression of TRIM32 and the prognosis of patients with lung cancer, an independent data set (The Human Protein Atlas website) was introduced. The expression and function analysis of TRIM32 in lung cancer cell lines were also performed by using cell counting kit-8, flow cytometry, transwell, real-time polymerase chain reaction and Western blot analysis. Our data showed that TRIM32 was overexpressed in lung cancer tissues and cell lines and was associated with a poor prognosis. TRIM32 silencing inhibited cell proliferation, migration, invasion, adhesion, and the activation of janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) signaling. The results showed knockdown of TRIM32 in NCI-H446 cells also inhibited cell growth in nude mice in the xenograft model. Additionally, TRIM32 overexpression promoted lung cancer cell proliferation and motility and mediated the expression of Bax, Bcl-2, cleaved caspase-3, matrix metalloproteinase-2 (MMP-2) and MMP-9 were inhibited by JAK2/STAT3 signaling inhibitor (AG490). Taken together, our findings suggest that TRIM32 may regulate lung cancer cell proliferation, apoptosis, and motility through activating the JAK2/STAT3-signaling pathway and may be a novel and promising target for lung cancer.
TRIM32 是三部分基序（TRIM）家族的成员，与肿瘤发生有关。然而，其在肺癌进展中的表达和潜在功能作用尚未完全了解。为了评估 TRIM32 的表达与肺癌患者预后之间的关系，引入了一个独立数据集（The Human Protein Atlas 网站）。还通过细胞计数试剂盒-8、流式细胞术、Transwell、实时聚合酶链反应和 Western blot 分析，对肺癌细胞系中 TRIM32 的表达和功能进行了分析。我们的数据表明，TRIM32 在肺癌组织和细胞系中过表达，与预后不良相关。TRIM32 沉默抑制细胞增殖、迁移、侵袭、黏附和 Janus 激酶 2（JAK2）/信号转导和转录激活因子 3（STAT3）信号的激活。结果表明，在 NCI-H446 细胞中敲低 TRIM32 也抑制了异种移植模型中裸鼠中的细胞生长。此外，TRIM32 过表达促进肺癌细胞增殖和迁移，并介导 Bax、Bcl-2、cleaved caspase-3、基质金属蛋白酶-2（MMP-2）和 MMP-9 的表达，JAK2/STAT3 信号抑制剂（AG490）可抑制其表达。总之，我们的研究结果表明，TRIM32 可能通过激活 JAK2/STAT3 信号通路调节肺癌细胞的增殖、凋亡和迁移，可能是肺癌的一个新的有前途的靶点。
