文章：

PARD6A通过Serpina3促进肺腺癌细胞增殖和侵袭

PARD6A promotes lung adenocarcinoma cell proliferation and invasion through Serpina3 

原文发布日期：2024-09-19 

英文摘要：

Par6α encoded by PARD6A is a member of the PAR6 family and is reported to promote cancer initiation and progression. PARD6A is frequently upregulated in different types of cancers, but its regulatory role in lung cancer progression is yet to be established. In this study, we analyzed the PARD6A expression in biopsies from lung adenocarcinoma (LUAD) patients, and the survival probability using LUAD tissue microarray (TMA) and online datasets from TCGA and GEO. We conducted in vitro and in vivo assays to assess the role of PARD6A in regulating lung cancer progression, including proliferation, wound healing, transwell, RNA-seq, and subcutaneous tumor mice models. Our findings revealed that PARD6A is highly expressed in cancer tissues from LUAD patients and is associated with poor prognosis in LUAD patients. In vitro assays showed that PARD6A promoted cell proliferation, migration, and invasion. The transcriptome sequencing identified Serpina3 as one of the key downstream molecules of PARD6A. Ectopic expression of Serpina3 rescued impaired proliferation, migration, and invasion in PARD6A-knocking down H1299 cells, whereas silencing Serpina3 impeded enhanced proliferation, migration, and invasion in PARD6A-overexpressing H1975 cells. Our findings suggest that PARD6A promotes lung cancer progression by inducing Serpina3, which may be a promising therapeutic target. 

摘要翻译：

由PARD6A基因编码的Par6α是PAR6家族成员，据报道可促进癌症的发生与发展。PARD6A在多种癌症类型中频繁上调表达，但其在肺癌进展中的调控作用尚不明确。本研究通过肺癌腺癌（LUAD）患者活检样本、组织微阵列（TMA）以及TCGA和GEO在线数据集，分析了PARD6A的表达水平与患者生存概率。我们通过体外和体内实验评估了PARD6A在调控肺癌进展中的作用，包括增殖实验、伤口愈合实验、Transwell实验、RNA测序以及皮下移植瘤小鼠模型。研究结果显示，PARD6A在LUAD患者的癌组织中高表达，且与患者不良预后相关。体外实验表明PARD6A能促进细胞增殖、迁移和侵袭。转录组测序发现Serpina3是PARD6A的关键下游分子之一。过表达Serpina3可挽救PARD6A敲降的H1299细胞中受损的增殖、迁移和侵袭能力，而沉默Serpina3则能抑制PARD6A过表达的H1975细胞中增强的恶性表型。我们的研究结果表明PARD6A通过诱导Serpina3表达促进肺癌进展，Serpina3可能成为潜在的治疗靶点。

原文链接：

PARD6A promotes lung adenocarcinoma cell proliferation and invasion through Serpina3