Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur Campus, Chennai, Tamil Nadu, 603203, India.
J Membr Biol. 2024 Aug;257(3-4):231-243. doi: 10.1007/s00232-024-00311-6. Epub 2024 Mar 28.
Progesterone Receptor Membrane Component 1 (PGRMC1) is a candidate oncogene with a prominent involvement in the pathogenesis of diverse cancers (ovarian, thyroid, breast, colon, head, and neck). Our study ascertains the ability of PGRMC1 to influence WNT members in the non-small cell lung cancer subtype-lung adenocarcinoma (LUAD) and participates in augmented cell proliferation and migration. Both computational and in vitro experimental analyses were performed in this study. Gene silencing, in vitro assays, gene expression & and protein expression studies were performed to ascertain the role of PGRMC1 in LUAD cells. The computational analysis, PGRMC1 gene level expression was analysed using the microarray gene expression omnibus datasets (GSE27262; GSE18842) to compare LUAD tumours and normal tissues. Concurrently, the gene expression profiling interactive analysis of PGRMC1 and Kaplan-Meier survival analysis revealed a decreasing patient survival rate with an increasing PGRMC1 gene expression in LUAD tumour samples. Interestingly, the experimental gene silencing studies were conducted in vitro (si-PGRMC1 Vs si-Control) to understand the essential role of PGRMC1 in regulating WNT-associated genes (WNT1, WNT5A, and WNT11). Comparative experimental cell migration and spheroid formation assays (si-PGRMC1 Vs si-Control) in vitro showed a strong association between PGRMC1 and LUAD. In vitro expression analysis using real-time PCR and western blot further confirmed the connecting link between PGRMC1 and WNT5A compared to other WNT member genes (WNT1 and WNT11) in LUAD. The computational and experimental analyses agreed with one another.
孕激素受体膜成分 1(PGRMC1)是一种候选癌基因,其在多种癌症(卵巢癌、甲状腺癌、乳腺癌、结肠癌、头颈部癌)的发病机制中具有显著作用。我们的研究确定了 PGRMC1 影响非小细胞肺癌亚型-肺腺癌(LUAD)中 WNT 成员的能力,并参与了增强的细胞增殖和迁移。本研究进行了计算和体外实验分析。进行基因沉默、体外测定、基因表达和蛋白质表达研究,以确定 PGRMC1 在 LUAD 细胞中的作用。通过使用微阵列基因表达综合数据集(GSE27262;GSE18842)进行计算分析,分析 PGRMC1 基因水平表达,以比较 LUAD 肿瘤和正常组织。同时,PGRMC1 基因表达的基因表达谱交互分析和 Kaplan-Meier 生存分析显示,LUAD 肿瘤样本中 PGRMC1 基因表达增加与患者生存率降低相关。有趣的是,进行了体外实验基因沉默研究(si-PGRMC1 与 si-Control),以了解 PGRMC1 在调节 WNT 相关基因(WNT1、WNT5A 和 WNT11)中的重要作用。体外比较实验细胞迁移和球体形成测定(si-PGRMC1 与 si-Control)显示,PGRMC1 与 LUAD 之间存在很强的关联。体外实时 PCR 和 Western blot 表达分析进一步证实了 PGRMC1 与 WNT5A 之间的联系,而与其他 WNT 成员基因(WNT1 和 WNT11)相比,在 LUAD 中。计算和实验分析相互一致。