Chromodomain helicase DNA-binding protein 4 (CHD4) has been shown to contribute to DNA repair and cell cycle promotion; however, its roles in cancer initiation and progression remain largely unknown. This study aimed to demonstrate the role of CHD4 in the development of non-small cell lung cancer (NSCLC) and determine the potential mechanisms of action. By using immunohistochemistry, the expression levels were evaluated in both cancer and non-cancerous tissues. Subsequently, CHD4 knockdown and overexpression strategies were employed to investigate the effects of CHD4 on cell proliferation, migration, along with the growth and formation of tumors in a xenografts mouse model. The protein expression levels of CHD4, PHF5A and ROCK/RhoA markers were determined by Western blot analysis. Compared with non-cancerous tissues, CHD4 was overexpressed in cancer tissues and CHD4 expression levels were closely related to clinical parameters of NSCLC patients. In H292 and PC-9 cell lines, CHD4 overexpression could promote the proliferative and migratory potential of NSCLC cells. Furthermore, down-regulation of CHD4 could reduce the proliferative and migratory ability in A549 and H1299 cell lines. Meanwhile, knockdown of CHD4 could decrease the tumorigenicity in nude mice. Finally, we demonstrated that one of the mechanisms underlying the promotive effect of CHD4 on NSCLC proliferation and migration may be through its interaction with PHD finger protein 5A (PHF5A) and subsequent activation of the RhoA/ROCK signaling pathway. CHD4, which is highly expressed in cancer tissue, could be an independent prognostic factor for NSCLC patients. CHD4 plays an important role in regulating the proliferative and migratory abilities of NSCLC via likely the RhoA/ROCK pathway by regulating PHF5A.

中文翻译：

---

CHD4通过调节PHF5A通过RhoA / ROCK途径介导非小细胞肺癌的增殖和迁移

染色体域解旋酶DNA结合蛋白4（CHD4）已被证明有助于DNA修复和细胞周期的促进。然而，它在癌症的发生和发展中的作用仍然未知。这项研究旨在证明CHD4在非小细胞肺癌（NSCLC）的发展中的作用，并确定潜在的作用机制。通过使用免疫组织化学，评估了癌组织和非癌组织中的表达水平。随后，采用CHD4敲低和过表达策略来研究CHD4在异种移植小鼠模型中对细胞增殖，迁移以及肿瘤的生长和形成的影响。通过蛋白质印迹分析确定CHD4，PHF5A和ROCK / RhoA标记的蛋白表达水平。与非癌组织相比 CHD4在癌症组织中过表达，CHD4表达水平与NSCLC患者的临床参数密切相关。在H292和PC-9细胞系中，CHD4过表达可能促进NSCLC细胞的增殖和迁移潜能。此外，CHD4的下调可能会降低A549和H1299细胞系的增殖和迁移能力。同时，敲低CHD4可降低裸鼠的致瘤性。最后，我们证明了CHD4对NSCLC增殖和迁移的促进作用的潜在机制之一可能是其与PHD指状蛋白5A（PHF5A）的相互作用以及随后的RhoA / ROCK信号通路的激活。在癌症组织中高表达的CHD4可能是NSCLC患者的独立预后因素。