Department of Respiratory and Critical Care Medicine, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, 710004, Shaanxi Province, PR China.
Department of Cardiovascular Disease, Xi'an No.1 Hospital, Xi'an, 710002, Shaanxi Province, PR China.
Mol Cell Probes. 2020 Oct;53:101628. doi: 10.1016/j.mcp.2020.101628. Epub 2020 Jul 1.
PDZ and LIM domain containing protein 2 (PDLIM2) has been identified as a vital tumor-associated gene that is aberrantly expressed in various types of tumors. Yet, the involvement of PDLIM2 in non-small cell lung cancer (NSCLC) is currently undetermined. The design of the current study was to evaluate whether PDLIM2 plays a role in NSCLC. We found that PDLIM2 expression was commonly decreased in NSCLC tissues. Moreover, low expression of PDLIM2 was also detected in NSCLC cell lines and demethylation treatment restored PDLIM2 expression. The re-expression of PDLIM2 impeded the proliferative, colony-forming, and invasive capabilities of NCLCL cells. In contrast, depletion of PDLIM2 markedly enhanced the malignant behaviors of NSCLC cells. Notably, PDLIM2 overexpression downregulated the expression of nuclear factor (NF)-κB p65 subunit and repressed NF-κB transcription reporter activity in NSCLC cells. The overexpression of p65 significantly reversed PDLIM2-mediated antitumor effects in NSCLC cells. Additionally, the Xenograft tumor formation assay revealed that the overexpression of PDLIM2 markedly restricted the tumor growth of NSCLC in vivo. Overall, our study confirms that PDLIM2 acts as a tumor-inhibitor in NSCLC through the inactivation of NF-κB, suggesting PDLIM2 as a candidate therapeutic target for NSCLC.
PDZ 和 LIM 结构域蛋白 2（PDLIM2）已被鉴定为一种重要的肿瘤相关基因，在各种类型的肿瘤中异常表达。然而，PDLIM2 在非小细胞肺癌（NSCLC）中的作用尚不清楚。本研究旨在评估 PDLIM2 是否在 NSCLC 中发挥作用。我们发现 PDLIM2 在 NSCLC 组织中普遍表达下调。此外，在 NSCLC 细胞系中也检测到 PDLIM2 表达降低，去甲基化处理可恢复 PDLIM2 的表达。PDLIM2 的重新表达抑制了 NCLCL 细胞的增殖、集落形成和侵袭能力。相反，PDLIM2 的耗竭显著增强了 NSCLC 细胞的恶性行为。值得注意的是，PDLIM2 的过表达下调了 NSCLC 细胞中核因子（NF）-κB p65 亚基的表达，并抑制了 NF-κB 转录报告基因活性。p65 的过表达显著逆转了 PDLIM2 介导的 NSCLC 细胞中的抗肿瘤作用。此外，异种移植肿瘤形成实验表明，PDLIM2 的过表达显著限制了 NSCLC 体内肿瘤的生长。总之，我们的研究证实 PDLIM2 通过失活 NF-κB 在 NSCLC 中发挥肿瘤抑制作用，提示 PDLIM2 是 NSCLC 的候选治疗靶点。
