Department of Thoracic Surgery, Sichuan Cancer Hospital and Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan 610041, P.R. China.
Department of Thoracic Surgery, First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650000, P.R. China.
Oncol Rep. 2018 Nov;40(5):3040-3048. doi: 10.3892/or.2018.6704. Epub 2018 Sep 13.
Period2 (Per2) is a key circadian clock gene, and its deregulation contributes to tumour development, including breast cancer. However, the biological function and clinicopathological significance of Per2 in non‑small cell lung cancer (NSCLC) remain unclear. The present study aimed to explore the role of Per2 and its relative clinical significance in NSCLC. To analyse Per2 expression in NSCLC specimens, reverse transcription‑quantitative polymerase chain reaction was performed, and the results indicated that Per2 expression was markedly downregulated in 83.87% (26/31) of NSCLC samples compared with their adjacent matched tissues. Increased Per2 expression was associated with increased differentiation (P<0.01) and reduced lymph node metastasis (P<0.0001). Functional studies identified that enhancing Per2 expression in A549 cells by lentivirus transduction not only significantly suppressed cell growth, migration and invasion (P<0.05) but also inhibited NSCLC growth and metastasis in vivo. Animal studies and histopathological analysis identified that Per2 expression in A549 cells not only markedly increased expression of tumour anti‑oncogenes Bax, P53 and P21 but also inhibited expression of pro‑oncogenes vascular endothelial growth factor, CD44 and c‑Myc. These results indicate that the loss of Per2 is one of the factors underlying tumourigenesis in NSCLC, and it may function as a novel molecular target for NSCLC.
周期蛋白 2（Per2）是一个关键的生物钟基因，其失调会导致肿瘤的发展，包括乳腺癌。然而，Per2 在非小细胞肺癌（NSCLC）中的生物学功能和临床病理意义尚不清楚。本研究旨在探讨 Per2 在 NSCLC 中的作用及其相对临床意义。为了分析 NSCLC 标本中 Per2 的表达，进行了逆转录-定量聚合酶链反应，结果表明，与相邻配对组织相比，83.87%（26/31）的 NSCLC 样本中 Per2 的表达明显下调。Per2 表达的增加与分化程度的增加（P<0.01）和淋巴结转移的减少（P<0.0001）有关。功能研究表明，通过慢病毒转导增强 A549 细胞中的 Per2 表达不仅显著抑制细胞生长、迁移和侵袭（P<0.05），而且还抑制了 NSCLC 在体内的生长和转移。动物研究和组织病理学分析表明，A549 细胞中 Per2 的表达不仅明显增加了肿瘤抑癌基因 Bax、P53 和 P21 的表达，还抑制了原癌基因血管内皮生长因子、CD44 和 c-Myc 的表达。这些结果表明，Per2 的缺失是 NSCLC 肿瘤发生的因素之一，它可能是 NSCLC 的一个新的分子靶点。
