Abstract：
UNASSIGNED: DEAD-box helicase 27 (DDX27), a member of the DEAD-Box nucleic acid helicase family, holds an elusive role in oral squamous cell carcinoma (OSCC). This study aims to unravel the regulatory functions of DDX27 in OSCC and explore its downstream targets.
METHODS: A commercial oral squamous cell carcinoma (OSCC) tissue microarray (TMA) was utilized. We analyzed differentially expressed genes in OSCC through the GEO database. Target gene silencing was achieved using the shRNA-mediated lentivirus method. Coexpedia analysis identified co-expressed genes associated with DDX27. Additionally, a Co-Immunoprecipitation (Co-IP) experiment confirmed the protein interaction between DDX27 and CSE1L. Xenograft tumor models were employed to evaluate DDX27\'s role in OSCC tumor formation.
RESULTS: Elevated DDX27 expression in OSCC correlated with a higher pathological grade. DDX27 knockdown resulted in decreased cell proliferation, increased apoptosis, inhibited cell migration, and induced G2/M phase cell cycle arrest, as well as impaired tumor outgrowth. Coexpedia analysis identified STAU1, NELFCD, and CSE1L as top co-expressed genes. Lentiviral vectors targeting STAU1, NELFCD, and CSE1L revealed that silencing CSE1L significantly impaired cell growth, indicating it as a downstream target of DDX27. Cell rescue experiments demonstrated that increased DDX27 levels ameliorated cell proliferation, attenuated apoptosis, and CSE1L depletion blocked cell development induced by DDX27 overexpression.
CONCLUSIONS: This study highlighted DDX27 as a potential therapeutic target for OSCC treatment, shedding light on its crucial role in OSCC development. Targeting DDX27 or its downstream effector, CSE1L, holds promise for innovative OSCC therapies.
METHODS: A commercial oral squamous cell carcinoma (OSCC) tissue microarray (TMA) was utilized. We analyzed differentially expressed genes in OSCC through the GEO database. Target gene silencing was achieved using the shRNA-mediated lentivirus method. Coexpedia analysis identified co-expressed genes associated with DDX27. Additionally, a Co-Immunoprecipitation (Co-IP) experiment confirmed the protein interaction between DDX27 and CSE1L. Xenograft tumor models were employed to evaluate DDX27\'s role in OSCC tumor formation.
RESULTS: Elevated DDX27 expression in OSCC correlated with a higher pathological grade. DDX27 knockdown resulted in decreased cell proliferation, increased apoptosis, inhibited cell migration, and induced G2/M phase cell cycle arrest, as well as impaired tumor outgrowth. Coexpedia analysis identified STAU1, NELFCD, and CSE1L as top co-expressed genes. Lentiviral vectors targeting STAU1, NELFCD, and CSE1L revealed that silencing CSE1L significantly impaired cell growth, indicating it as a downstream target of DDX27. Cell rescue experiments demonstrated that increased DDX27 levels ameliorated cell proliferation, attenuated apoptosis, and CSE1L depletion blocked cell development induced by DDX27 overexpression.
CONCLUSIONS: This study highlighted DDX27 as a potential therapeutic target for OSCC treatment, shedding light on its crucial role in OSCC development. Targeting DDX27 or its downstream effector, CSE1L, holds promise for innovative OSCC therapies.
摘要：
■DEAD-box解旋酶27(DDX27),DEAD-Box核酸解旋酶家族的一员,在口腔鳞状细胞癌（OSCC）中具有难以捉摸的作用。本研究旨在揭示DDX27在OSCC中的调控功能，并探索其下游靶点。
方法：使用商业口腔鳞状细胞癌（OSCC）组织微阵列（TMA）。我们通过GEO数据库分析了OSCC中差异表达的基因。使用shRNA介导的慢病毒方法实现靶基因沉默。Coexpedia分析确定了与DDX27相关的共表达基因。此外,免疫共沉淀(Co-IP)实验证实了DDX27和CSE1L之间的蛋白质相互作用。采用异种移植肿瘤模型评估DDX27在OSCC肿瘤形成中的作用。
结果：DDX27在OSCC中的表达升高与更高的病理分级相关。DDX27敲低导致细胞增殖减少，细胞凋亡增加，抑制细胞迁移，并诱导G2/M期细胞周期停滞，以及受损的肿瘤生长。Coexpedia分析确定了STAU1，NELFCD，和CSE1L作为最高共表达基因。靶向STAU1，NELFCD的慢病毒载体，和CSE1L表明沉默CSE1L显著损害细胞生长，将其指示为DDX27的下游目标。细胞拯救实验表明，增加DDX27水平改善细胞增殖，细胞凋亡减弱，和CSE1L耗竭阻断DDX27过表达诱导的细胞发育。
结论：本研究强调DDX27是OSCC治疗的潜在治疗靶点，阐明其在OSCC发展中的关键作用。靶向DDX27或其下游效应器，CSE1L,为创新的OSCC疗法提供了希望。
方法：使用商业口腔鳞状细胞癌（OSCC）组织微阵列（TMA）。我们通过GEO数据库分析了OSCC中差异表达的基因。使用shRNA介导的慢病毒方法实现靶基因沉默。Coexpedia分析确定了与DDX27相关的共表达基因。此外,免疫共沉淀(Co-IP)实验证实了DDX27和CSE1L之间的蛋白质相互作用。采用异种移植肿瘤模型评估DDX27在OSCC肿瘤形成中的作用。
结果：DDX27在OSCC中的表达升高与更高的病理分级相关。DDX27敲低导致细胞增殖减少，细胞凋亡增加，抑制细胞迁移，并诱导G2/M期细胞周期停滞，以及受损的肿瘤生长。Coexpedia分析确定了STAU1，NELFCD，和CSE1L作为最高共表达基因。靶向STAU1，NELFCD的慢病毒载体，和CSE1L表明沉默CSE1L显著损害细胞生长，将其指示为DDX27的下游目标。细胞拯救实验表明，增加DDX27水平改善细胞增殖，细胞凋亡减弱，和CSE1L耗竭阻断DDX27过表达诱导的细胞发育。
结论：本研究强调DDX27是OSCC治疗的潜在治疗靶点，阐明其在OSCC发展中的关键作用。靶向DDX27或其下游效应器，CSE1L,为创新的OSCC疗法提供了希望。
