Wu Lei, Wan Shan, Li Jinfan, Xu Yiying, Lou Xiaoli, Sun Maomin, Wang Shouli
Department of Pathology, School of Biology and Basic Medical Sciences, Soochow University, Suzhou, Jiangsu 215123, P.R. China.
Department of Pathology, The Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang 310009, P.R. China.
Oncol Lett. 2021 May;21(5):411. doi: 10.3892/ol.2021.12672. Epub 2021 Mar 22.
E2F transcription factor 3 (E2F3) plays a vital role in the development of various types of cancer. To verify whether E2F3 is a suitable biomarker for the prognosis of lung cancer, bioinformatics analysis was performed to determine the differential expression level of E2F3 in lung cancer and the surrounding non-tumor tissues, and the results were confirmed in a NSCLC cell line and a tissue microarray (TMA). The relevance of E2F3 in non-small cell lung cancer (NSCLC) was investigated in 19 studies from the Oncomine database and confirmed in The Cancer Genome Atlas database. In the lung cancer cell line A549, the inhibition of E2F3 mRNA expression level led to decreased tumor cell viability and cell migration, which was determined by a Cell Counting Kit-8 and wound healing assays, respectively. Immunohistochemistry analyses of E2F3, Bcl-2, Bax and caspase-3 were performed in the NSCLC TMA (n=50). The assessment of TMA detected the increase of E2F3 protein expression level in the tumor tissues, as compared with that in the non-tumor tissues, which was also correlated with the increase in expression of Bcl-2 in tumors. Analysis of the clinical data from patients with NSCLC revealed that the overexpression of E2F3 was associated with early lymphatic spreading, and poor patient survival time. The OncomiR website was used to predict the E2F3 upstream microRNAs and determine their prognostic value in patients with NSCLC. The results from the present study revealed that E2F3 was overexpressed at both the transcriptional and translational levels in NSCLC tissues, as compared with that in non-tumor tissues. The overexpression of E2F3 was associated with the upregulation of the anti-apoptotic factor, Bcl-2, which may contribute to uncontrolled tumor growth. Thus, E2F3 was shown to have important oncogenic properties in the development of NSCLC, and it may become a potential biomarker for patients with NSCLC.
E2F转录因子3（E2F3）在各类癌症的发展过程中发挥着至关重要的作用。为了验证E2F3是否为肺癌预后的合适生物标志物，我们进行了生物信息学分析，以确定E2F3在肺癌组织及周围非肿瘤组织中的差异表达水平，并在非小细胞肺癌（NSCLC）细胞系和组织芯片（TMA）中对结果进行了验证。通过Oncomine数据库中的19项研究调查了E2F3在非小细胞肺癌（NSCLC）中的相关性，并在癌症基因组图谱数据库中得到了证实。在肺癌细胞系A549中，E2F3 mRNA表达水平的抑制导致肿瘤细胞活力降低和细胞迁移减少，这分别通过细胞计数试剂盒-8和伤口愈合试验确定。在NSCLC组织芯片（n = 50）中进行了E2F3、Bcl-2、Bax和caspase-3的免疫组织化学分析。TMA评估检测到肿瘤组织中E2F3蛋白表达水平高于非肿瘤组织，这也与肿瘤中Bcl-2表达的增加相关。对NSCLC患者临床数据的分析表明，E2F3的过表达与早期淋巴转移及患者较差的生存时间相关。使用OncomiR网站预测E2F3上游的微小RNA，并确定它们在NSCLC患者中的预后价值。本研究结果显示，与非肿瘤组织相比，NSCLC组织中E2F3在转录和翻译水平均过表达。E2F3的过表达与抗凋亡因子Bcl-2的上调相关，这可能导致肿瘤生长失控。因此，E2F3在NSCLC的发展中显示出重要的致癌特性，它可能成为NSCLC患者的潜在生物标志物。
