Department of Thoracic Surgery, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Department of Thoracic Surgery, Beijing Sixth Hospital, Beijing, China.
J Cell Mol Med. 2024 Jun;28(12):e18488. doi: 10.1111/jcmm.18488.
MCM8 is a helicase, which participates in DNA replication and tumorigenesis and is upregulated in many human cancers, including lung cancer (LC); however, the function of MCM8 in LC tumour progression is unclear. In this study, we found that MCM8 was expressed at high levels in LC cells and tissues. Further, MCM8 upregulation was associated with advanced tumour grade and lymph node metastasis, and indicated poor prognosis. Silencing of MCM8 suppressed cell growth and migration in vitro and in vivo, while ectopic MCM8 expression promoted cell cycle progression, as well as cell migration, proliferation, and apoptosis. Mechanistically, DNAJC10 was identified as a downstream target of MCM8, using gene array and CO-IP assays. DNAJC10 overexpression combatted the inhibitory activity of MCM8 knockdown on LC progression, while silencing DNAJC10 alleviated the oncogenic function of MCM8 overexpression. MCM8 expression was positively correlated with that of DNAJC10 in LC samples from The Cancer Genome Atlas database, and DNAJC10 upregulation was also associated with poor overall survival of patients with LC. This study indicated that MCM8/DNAJC10 axis plays an important role in in LC development, and maybe as a new potential therapeutic target or a diagnostic biomarker for treating patients with LC.
MCM8 是一种解旋酶,参与 DNA 复制和肿瘤发生,在许多人类癌症中上调,包括肺癌(LC);然而,MCM8 在 LC 肿瘤进展中的作用尚不清楚。在这项研究中,我们发现 MCM8 在 LC 细胞和组织中表达水平较高。此外,MCM8 的上调与肿瘤分级较高和淋巴结转移有关,并预示着预后不良。MCM8 的沉默抑制了体外和体内的细胞生长和迁移,而过表达 MCM8 则促进了细胞周期进程以及细胞迁移、增殖和凋亡。通过基因阵列和 CO-IP 检测,鉴定出 DNAJC10 是 MCM8 的下游靶标。DNAJC10 的过表达抵消了 MCM8 敲低对 LC 进展的抑制活性,而沉默 DNAJC10 则减轻了 MCM8 过表达的致癌功能。在来自癌症基因组图谱数据库的 LC 样本中,MCM8 的表达与 DNAJC10 的表达呈正相关,并且 DNAJC10 的上调也与 LC 患者的总体生存不良相关。这项研究表明,MCM8/DNAJC10 轴在 LC 发生发展中起着重要作用,可能成为治疗 LC 患者的新的潜在治疗靶点或诊断生物标志物。