Department of Thoracic Surgery, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, PR China.
Department of Pediatrics, Qingpu Branch of Zhongshan Hospital Affiliated to Fudan University, Shanghai 201700, PR China.
Life Sci. 2021 Jan 15;265:118768. doi: 10.1016/j.lfs.2020.118768. Epub 2020 Nov 17.
Non-small cell lung cancer (NSCLC) patients have a lower 5-year survival rate, and the distant tumor metastasis and drug resistance are the main reasons for the high mortality. RECQL5, a member of RecQ helicases family, has been linked to tumorigenesis of various cancers expect NSCLC. In the current study, analysis with the Cancer Genome Atlas (TCGA) dataset showed that the level of RECQL5 was elevated in LUAD (Lung Adenocarcinoma) and LUSC (lung squamous carcinomas), two major subtypes of NSCLC, which was confirmed by immunohistochemistry staining on Tissue array slides. The level of RECQL5 was also elevated in NSCLC cell lines. Further, Kaplan-Meier analysis of TCGA dataset suggested that the up-regulated RECQL5 was associated with poor prognosis of LUAD, but not with that of LUSC. Knockdown of RECQL5 significantly inhibited the invasion and migration of NSCLC cells, and suppressed epithelial-mesenchymal transition (EMT) as indicated by the changes of EMT-related proteins, while overexpression of RECQL5 displayed reverse effects. Lung metastasis was also suppressed by RECQL5 knockdown. Additionally, the addition of Akt inhibitor LY294002 reversed the effects of RECQL5 overexpression on cell migration, invasion and EMT. Moreover, knockdown of RECQL5 increased the apoptosis of cisplatin-resistant A549 cell line (A549/DDP) caused by cisplatin treatment. In summary, RECQL5 contributed to the metastasis of NSCLC and assisted NSCLC cells incompletely response to cisplatin therapy, and could be considered as a biomarker or clinical target for NSCLC.
非小细胞肺癌（NSCLC）患者的 5 年生存率较低，远处肿瘤转移和耐药性是导致高死亡率的主要原因。RECQL5 是 RecQ 解旋酶家族的成员，与多种癌症（除 NSCLC 外）的肿瘤发生有关。在本研究中，通过癌症基因组图谱（TCGA）数据集的分析表明，RECQL5 在 LUAD（肺腺癌）和 LUSC（肺鳞癌）两种 NSCLC 的主要亚型中上调，组织阵列幻灯片的免疫组织化学染色对此进行了验证。RECQL5 的水平也在 NSCLC 细胞系中上调。此外，TCGA 数据集的 Kaplan-Meier 分析表明，上调的 RECQL5 与 LUAD 的预后不良相关，但与 LUSC 无关。RECQL5 的敲低显著抑制了 NSCLC 细胞的侵袭和迁移，并通过 EMT 相关蛋白的变化抑制了上皮-间充质转化（EMT），而 RECQL5 的过表达则显示出相反的效果。RECQL5 的敲低也抑制了肺转移。此外，Akt 抑制剂 LY294002 的添加逆转了 RECQL5 过表达对细胞迁移、侵袭和 EMT 的影响。此外，RECQL5 的敲低增加了顺铂耐药 A549 细胞系（A549/DDP）在顺铂处理下的细胞凋亡。总之，RECQL5 促进了 NSCLC 的转移，并协助 NSCLC 细胞不完全对顺铂治疗产生反应，因此可被视为 NSCLC 的生物标志物或临床靶点。
