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

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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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Acknowledgements

We are grateful and humbly thank Dr. Satish Ramalingam and Dr. A. Devi for providing antibodies as gifts to perform protein expression studies in this work.

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The study was not supported by any form of a grant.

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  1. Department of Genetic Engineering, SRM Institute of Science and Technology, Kattankulathur Campus, Chennai, Tamil Nadu, 603203, India

    Solaipriya Solairaja & Sivaramakrishnan Venkatabalasubramanian

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  1. Solaipriya Solairaja
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  2. Sivaramakrishnan Venkatabalasubramanian
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VSRK and SS contributed to the conceptualization of the idea, computational result validation, providing resources, and design of this manuscript. SS and VSRK contributed to the experimental analysis, drafting, and editing of the manuscript. All the authors have confirmed the integrity of the manuscript.

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Correspondence to Sivaramakrishnan Venkatabalasubramanian.

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Solairaja, S., Venkatabalasubramanian, S. Beyond Hormones: Investigating the Impact of Progesterone Receptor Membrane Component 1 in Lung Adenocarcinoma. J Membrane Biol (2024). https://doi.org/10.1007/s00232-024-00311-6

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