Department of Pulmonary and Critical Care Medicine, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China.
Department of Respiratory Medicine, Weihai Municipal Hospital, Weihai 264200, China.
Int J Med Sci. 2021 Jan 1;18(2):494-504. doi: 10.7150/ijms.49041. eCollection 2021.
The molecular signatures of lung adenocarcinoma (LUAD) are not well understood. Centromere protein F (CENPF) has been shown to promote oncogenesis in many cancers; however, its role in LUAD has not been illustrated. We explored the role of CENPF in LUAD. CENPF expression level was investigated in public online database firstly, the prognosis of CENPF in LUAD were also assessed by Kaplan-Meier analysis. Then quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was performed using 13 matched pairs of clinical LUAD tissue samples. Subsequently, the impact of CENPF expression on cell proliferation, cell cycle, apoptosis, colony formation was investigated by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), flow cytometric analysis and colony formation assay, respectively. Finally, experimental xenograft lung cancer model of nude mice armpit of right forelimb to determine the effect of CENPF on LUAD tumorigenesis. CENPF mRNA expression was significantly elevated in LUAD tissues compared with adjacent non-tumor lung tissues in Gene Expression Profiling Interactive Analysis (GEPIA) ( < 0.001). Up-regulated CENPF was remarkably positively associated with pathological stage, relapse free survival (RFS) as well as overall survival (OS) of LUAD patients. Besides, CENPF knockdown greatly suppressed A549 cell proliferation, induced S phase arrest, promoted apoptosis and decreased colony numbers of LUAD cells. Furthermore, knockdown of CENPF significantly inhibited the tumor growth of the LUAD cells in an experimental xenograft lung cancer model of nude mice armpit of right forelimb. Taken together, these results demonstrated that CENPF may serve as a potential biomarker of prognostic relevance and a potential therapeutic target for LUAD.
肺腺癌（LUAD）的分子特征尚不清楚。着丝粒蛋白 F（CENPF）已被证明在许多癌症中促进肿瘤发生；然而，其在 LUAD 中的作用尚未阐明。我们探讨了 CENPF 在 LUAD 中的作用。首先在公共在线数据库中研究了 CENPF 的表达水平，并用 Kaplan-Meier 分析评估了 CENPF 在 LUAD 中的预后。然后使用 13 对临床 LUAD 组织样本进行了定量逆转录-聚合酶链反应（qRT-PCR）。随后，通过 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐（MTT）、流式细胞术分析和集落形成测定分别研究了 CENPF 表达对细胞增殖、细胞周期、凋亡和集落形成的影响。最后，通过裸鼠右前肢腋窝实验性异种移植肺癌模型确定 CENPF 对 LUAD 肿瘤发生的影响。在基因表达谱交互分析（GEPIA）中，与相邻非肿瘤肺组织相比，LUAD 组织中的 CENPF mRNA 表达显著升高（<0.001）。上调的 CENPF 与 LUAD 患者的病理分期、无复发生存（RFS）和总生存（OS）显著正相关。此外，CENPF 敲低可显著抑制 A549 细胞增殖，诱导 S 期阻滞，促进细胞凋亡，并降低 LUAD 细胞的集落数。此外，在裸鼠右前肢腋窝实验性异种移植肺癌模型中，CENPF 敲低显著抑制了 LUAD 细胞的肿瘤生长。总之，这些结果表明 CENPF 可能作为 LUAD 相关预后的潜在生物标志物和潜在治疗靶点。
