Department of Respiration, The First Hospital of Jilin University, Changchun, 130021, China.
Intensive Care Unit, The First Hospital of Jilin University, Changchun, 130021, China.
Biochem Biophys Res Commun. 2020 Dec 10;533(3):354-361. doi: 10.1016/j.bbrc.2020.06.139. Epub 2020 Sep 19.
Non-small cell lung cancer (NSCLC) is a leading cause of tumor mortality worldwide. Nevertheless, the molecular mechanisms revealing NSCLC progression are still unclear. 5'-Nucleotidase domain containing 2 (NT5DC2), as a member of the NT5DC family, contains a haloacid dehalogenase motif localized in the N-terminus of these proteins. NT5DC2 plays an essential role in cancer development. The purpose of the study was to explore NT5DC2's role in tumorigenesis and its potential mechanisms in NSCLC. Our findings showed that NT5DC2 expression was significantly up-regulated in clinical NSCLC tissues compared to the paired non-tumor tissues. Functionally, NT5DC2 knockdown in A549 and H1299 cells markedly reduced cell proliferation, migration and invasion. On the contrary, NT5DC2 over-expression promoted NSCLC cell proliferative, migrative and invasive capacities. Additionally, NT5DC2 down-regulation significantly induced the G2 cell cycle arrest and apoptosis in NSCLC cells. Mechanistically, p53 might be a target of NT5DC2. The expression of p53 was highly induced in NSCLC cells with NT5DC2 knockdown, and opposite result was detected when NT5DC2 was over-expressed. Importantly, we found that NT5DC2 knockdown-restrained cell proliferation and -induced apoptosis was almost abrogated by p53 down-regulation in NSCLC cells, demonstrating that NT5DC2-regulated cell proliferation and apoptotic cell death in NSCLC was p53-dependent. Finally, we confirmed that reducing NT5DC2 could inhibit NSCLC tumorigenesis and hepatic metastasis in vivo. Collectively, these results suggested that NT5DC2 may be a potential driver of NSCLC, providing a new therapeutic target for the clinical treatment of NSCLC.
非小细胞肺癌（NSCLC）是全球肿瘤死亡的主要原因。然而，揭示 NSCLC 进展的分子机制仍不清楚。5'-核苷酸酶结构域包含 2（NT5DC2）作为 NT5DC 家族的一员，含有一个位于这些蛋白 N 端的卤酸脱卤酶基序。NT5DC2 在癌症发展中起着至关重要的作用。本研究旨在探讨 NT5DC2 在肿瘤发生中的作用及其在 NSCLC 中的潜在机制。我们的研究结果表明，与配对的非肿瘤组织相比，NT5DC2 在临床 NSCLC 组织中的表达显著上调。功能上，在 A549 和 H1299 细胞中敲低 NT5DC2 显著降低细胞增殖、迁移和侵袭。相反，NT5DC2 的过表达促进了 NSCLC 细胞的增殖、迁移和侵袭能力。此外，NT5DC2 下调显著诱导 NSCLC 细胞的 G2 细胞周期停滞和细胞凋亡。在机制上，p53 可能是 NT5DC2 的一个靶标。在敲低 NT5DC2 的 NSCLC 细胞中，p53 的表达被高度诱导，而当 NT5DC2 过表达时则检测到相反的结果。重要的是，我们发现 NT5DC2 敲低抑制的细胞增殖和诱导的细胞凋亡在 NSCLC 细胞中几乎被 p53 下调所消除，表明 NT5DC2 调节 NSCLC 中的细胞增殖和凋亡细胞死亡依赖于 p53。最后，我们证实了降低 NT5DC2 可以抑制 NSCLC 的体内肿瘤发生和肝转移。总之，这些结果表明 NT5DC2 可能是 NSCLC 的一个潜在驱动因素，为 NSCLC 的临床治疗提供了一个新的治疗靶点。
