Beyond Hormones: Investigating the Impact of Progesterone Receptor Membrane Component 1 in Lung Adenocarcinoma

The Journal of Membrane Biology Pub Date : 2024-03-28 DOI:10.1007/s00232-024-00311-6

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Abstract

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.

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超越激素：研究孕酮受体膜组件 1 对肺腺癌的影响

摘要 Progesterone Receptor Membrane Component 1（PGRMC1）是一种候选癌基因，主要参与多种癌症（卵巢癌、甲状腺癌、乳腺癌、结肠癌、头颈部癌症）的发病机制。我们的研究确定了 PGRMC1 在非小细胞肺癌亚型-肺腺癌（LUAD）中影响 WNT 成员的能力，并参与增强细胞增殖和迁移。本研究进行了计算和体外实验分析。为了确定 PGRMC1 在 LUAD 细胞中的作用，研究人员进行了基因沉默、体外实验、基因表达& 和蛋白质表达研究。通过计算分析，使用微阵列基因表达总集数据集（GSE27262；GSE18842）分析了 PGRMC1 基因水平的表达，以比较 LUAD 肿瘤和正常组织。同时，PGRMC1 基因表达谱交互分析和 Kaplan-Meier 生存分析显示，在 LUAD 肿瘤样本中，随着 PGRMC1 基因表达量的增加，患者的生存率也在下降。有趣的是，为了了解 PGRMC1 在调控 WNT 相关基因（WNT1、WNT5A 和 WNT11）中的重要作用，我们在体外进行了基因沉默实验研究（si-PGRMC1 Vs si-Control）。体外细胞迁移和球形细胞形成实验（si-PGRMC1 与 si-Control 对照）的比较结果表明，PGRMC1 与 LUAD 有密切联系。利用实时 PCR 和 Western 印迹进行的体外表达分析进一步证实，与其他 WNT 成员基因（WNT1 和 WNT11）相比，PGRMC1 和 WNT5A 与 LUAD 之间存在联系。计算分析和实验分析结果一致。图表摘要

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The Journal of Membrane Biology

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