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Drug Res (Stuttg) 2024; 74(04): 187-190
DOI: 10.1055/a-2273-2389
Short Communication

Preclinical Targeting of the PGRMC1-CK2 Axis with Silmitasertib: A Potential Strategy for Lung Adenocarcinoma Therapy

S. Solaipriya
1   Department of Genetic Engineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur Campus, Chennai - 603203, Tamil Nadu, India
,
M Anbalagan
2   Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana, USA
,
V. Sivaramakrishnan
1   Department of Genetic Engineering, College of Engineering and Technology, SRM Institute of Science and Technology, Kattankulathur Campus, Chennai - 603203, Tamil Nadu, India
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Abstract

Progesterone receptor membrane component 1 (PGRMC1) is a pleiotropic protein over-expressed in lung adenocarcinoma (LUAD). The precise molecular mechanisms underlying the signature motif of Casein kinase (CK2) presence in PGRMC1 and their role in LUAD remain unclear. X-ray crystallographic structure for CK2 and PGRMC1 from the PubChem database was obtained and subjected to protein-protein interaction (PPI) analysis to identify their interactions. In addition, the CK2 inhibitor – Silmitasertib was also utilised to understand the interaction between PGRMC1-CK2. The PPI complex (PGRMC1-CK2) and the PPI-ligand interaction analysis and their Molecular Dynamics (MD) studies revealed the stability of their interactions and critical amino acid contacts within the 5Ǻ vicinity of the CK2 signature motif "T/S-x-x-E/D". Moreover, in-vitro colony formation assay, migration assay, and gene expression analysis using quantitative Real-time PCR revealed that Silmitasertib (IC50–2.5 μM) was highly influential in suppressing the PGRMC1-CK2 expression axis. In conclusion, our study infers that PGRMC1-CK-2 axis inhibition could be a potential therapeutic option to limit the promotion and progression of lung cancer.

Keywords

CK2 signature motif - lung cancer - health and disease - bioinformatics - in-vitro

Supplementary material



Publication History

Received: 22 November 2023

Accepted: 13 February 2024

Article published online:
20 March 2024

© 2024. Thieme. All rights reserved.

Georg Thieme Verlag
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