Department of Respiratory Medicine, Anhui Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250021, P.R. China.
Department of Respiration and Critical Care Medicine, Anhui Provincial Key Laboratory of Clinical Basic Research on Respiratory Disease, The First Affiliated Hospital of Bengbu Medical College, Bengbu, Anhui 233004, P.R. China.
Int J Oncol. 2021 Jan;58(1):83-99. doi: 10.3892/ijo.2020.5154. Epub 2020 Dec 1.
Lung cancer is the most frequently diagnosed cancer and the leading cause of cancer‑associated mortality worldwide. In the present study, a novel molecular therapeutic target for lung cancer was investigated. The protein expression level of fidgetin‑like 1 (FIGNL1) in human lung cancer tissues was determined and its potential functions in the H1299 and A549 lung cancer cell lines was subsequently studied. In addition, the protein expression level of FIGNL1 in 109 lung cancer samples and corresponding para‑cancerous tissues was investigated, using immunohistochemical staining. RNA interference and overexpression of FIGNL1 was used to determine the role of FIGNL1 in regulating cell proliferation, and cDNA microarray analysis was performed to identify the potential regulatory pathways. Lastly, the potential role of FIGNL1 in regulating tumorigenesis in lungs and also the proliferation of lung cancer cells was investigated. Firstly, lung cancer tissues were found to express higher protein levels of FIGNL1 and was significantly associated with decreased cell proliferation, migration and invasion abilities, and enhanced cell death. Overexpression of FIGNL1 significantly promoted cell proliferation, including decreased arrest at the G1 phase of the cell cycle and apoptosis, as well as increased ability for fission and migration. These in vitro findings were consistent with the results of the cell‑line derived xenografts in BALB/c nude mice, where tumor growth was decreased when injected with cells transfected with shFIGNL1. Collectively, these results provide suggest that FIGNL1 is involved in cell growth and tumorigenesis.
肺癌是全球最常见的癌症,也是癌症相关死亡的主要原因。在本研究中,我们研究了一种肺癌的新型分子治疗靶点。测定了人肺癌组织中 fidgetin 样蛋白 1 (FIGNL1) 的蛋白表达水平,并随后研究了其在 H1299 和 A549 肺癌细胞系中的潜在功能。此外,采用免疫组织化学染色法检测了 109 例肺癌标本及相应癌旁组织中 FIGNL1 的蛋白表达水平。通过 RNA 干扰和过表达 FIGNL1 来确定 FIGNL1 在调节细胞增殖中的作用,并进行 cDNA 微阵列分析以鉴定潜在的调控途径。最后,研究了 FIGNL1 在调节肺肿瘤发生和肺癌细胞增殖中的潜在作用。首先,发现肺癌组织中 FIGNL1 的蛋白表达水平较高,且与细胞增殖、迁移和侵袭能力降低以及细胞死亡增加显著相关。FIGNL1 的过表达显著促进了细胞增殖,包括细胞周期 G1 期阻滞和凋亡减少,以及分裂和迁移能力增强。这些体外研究结果与 BALB/c 裸鼠衍生的细胞系异种移植的结果一致,当用 shFIGNL1 转染的细胞注射时,肿瘤生长减少。综上所述,这些结果表明 FIGNL1 参与了细胞生长和肿瘤发生。