PARD6A 编码的 Par6α 是 PAR6 家族的成员，据报道可促进癌症的发生和进展。 PARD6A 在不同类型的癌症中经常上调，但其在肺癌进展中的调节作用尚未确定。在这项研究中，我们分析了肺腺癌 (LUAD) 患者活检组织中 PARD6A 的表达，并使用 LUAD 组织微阵列 (TMA) 以及来自 TCGA 和 GEO 的在线数据集分析了生存概率。我们进行了体外和体内测定，以评估 PARD6A 在调节肺癌进展中的作用，包括增殖、伤口愈合、Transwell、RNA-seq 和皮下肿瘤小鼠模型。我们的研究结果表明，PARD6A 在 LUAD 患者的癌组织中高表达，并且与 LUAD 患者的不良预后相关。体外实验表明 PARD6A 促进细胞增殖、迁移和侵袭。转录组测序确定 Serpina3 是 PARD6A 的关键下游分子之一。 Serpina3 的异位表达可以挽救 PARD6A 敲低的 H1299 细胞中受损的增殖、迁移和侵袭，而沉默 Serpina3 则阻碍 PARD6A 过表达的 H1975 细胞中增殖、迁移和侵袭的增强。我们的研究结果表明，PARD6A 通过诱导 Serpina3 促进肺癌进展，这可能是一个有前途的治疗靶点。© 2024。作者获得 Springer Nature America, Inc. 的独家许可。

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.© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.