Laboratory Medicine Center, Affiliated Hospital of Nantong University, Nantong, China.
Department of Pathology, Affiliated Hospital of Nantong University, Nantong, China.
IUBMB Life. 2018 Apr;70(4):310-319. doi: 10.1002/iub.1727. Epub 2018 Feb 27.
Lung cancer, particularly non-small cell lung cancer (NSCLC), is one of main causes of mortality in cancer patients worldwide. It is necessary to seek effective biomarkers to improve diagnostic and therapeutic efficacies in human NSCLC. RTP801 is a stress-response protein that can be induced by many types of cellular stress such as hypoxia and DNA damage, produces different biological effects depending on cell type and context. Up to now, there is no direct evidence showing the expression and involvement of RTP801 in human NSCLC. Here, we found that the expression of RTP801 significantly increased in NSCLC tissues compared with that in normal lung and the level of RTP801 in peripheral blood of NSCLC patients was higher than that of healthy persons. Further study showed that knockdown of RTP801 induced by lentivirus encoded RTP801-shRNA markedly inhibited the proliferation of A549 and SW900 cells. Moreover, the inhibitor of PI3K significantly decreased the expression of RTP801 mRNA and protein and, at the same time, inhibited the proliferation of A549 and SW900 cells. Taken together, our study provides the novel and direct evidence that there is a close relationship between RTP801 and human NSCLC, and RTP801 can promote the proliferation of NSCLC cells which is regulated by PI3K signaling pathway, suggesting that RTP801 could be a potential biomarker for diagnosis and therapeutic target of human NSCLC. © 2018 IUBMB Life, 70(4):310-319, 2018.
肺癌,尤其是非小细胞肺癌(NSCLC),是全球癌症患者死亡的主要原因之一。有必要寻找有效的生物标志物,以提高人类 NSCLC 的诊断和治疗效果。RTP801 是一种应激反应蛋白,可被多种类型的细胞应激诱导,如缺氧和 DNA 损伤,根据细胞类型和环境产生不同的生物学效应。到目前为止,没有直接的证据表明 RTP801 在人类 NSCLC 中的表达和参与。在这里,我们发现 RTP801 的表达在 NSCLC 组织中明显高于正常肺组织,而 NSCLC 患者外周血中的 RTP801 水平高于健康人。进一步的研究表明,慢病毒编码的 RTP801-shRNA 下调 RTP801 的表达显著抑制了 A549 和 SW900 细胞的增殖。此外,PI3K 抑制剂显著降低了 RTP801 mRNA 和蛋白的表达,并同时抑制了 A549 和 SW900 细胞的增殖。总之,我们的研究提供了新的直接证据,表明 RTP801 与人类 NSCLC 之间存在密切关系,RTP801 可以促进 NSCLC 细胞的增殖,其受 PI3K 信号通路调节,提示 RTP801 可能是人类 NSCLC 的潜在诊断标志物和治疗靶点。