An in-silico approach to understand the potential role of Wnt inhibitory factor-1 (WIF-1) in the inhibition of the Wnt signalling pathway

Abstract

WIF1 (Wnt inhibitory factor 1) is a potent tumour suppressor gene which is epigenetically silenced in numerous malignancies. The associations of WIF1 protein with the Wnt pathway molecules have not been fully explored, despite their involvement in the downregulation of several malignancies. In the present study, a computational approach encompassing the expression, gene ontology analysis and pathway analysis is employed to obtain an insight into the role of the WIF1 protein. Moreover, the interaction of the WIF1 domain with the Wnt pathway molecules was carried out to ascertain the tumour-suppressive role of the domain, along with the determination of their plausible interactions. Initially, the protein-protein interaction network analysis endowed us with the Wnt ligands (such as Wnt1, Wnt3a, Wnt4, Wnt5a, Wnt8a and Wnt9a), along with the Frizzled receptors (Fzd1 and Fzd2) and the low-density lipoprotein complex (Lrp5/6) as the foremost interactors of the protein. Further, the expression analysis of the aforementioned genes and proteins was determined using The Cancer Genome Atlas to comprehend the significance of the signalling molecules in the major cancer subtypes. Moreover, the associations of the aforementioned macromolecular entities with the WIF1 domain were explored using the molecular docking studies, whereas the dynamics and stability of the assemblage were investigated using 100 ns molecular dynamics simulations. Therefore, providing us insights into the plausible roles of WIF1 in inhibiting the Wnt pathways in various malignancies.

Communicated by Ramaswamy H. Sarma

Keywords:

• In silico protein characterization
• MD simulations
• protein interactions
• WIF1
• Wnt signalling pathway

Acknowledgements

We greatly acknowledge the Department of Biotechnology (BT/PR44695/NER/95/1880/2021 and BT/PR41449/NER/95/1687/837 2020) under DBT Programme Support Facility of Biosciences and Bioengineering, the Centre for Nanotechnology (ICMR Centre for Excellence, Grant no. 5/3/8/20/2019-ITR, INUP, MeitY Grant no. 5(1)/2021-NANO) at IIT Guwahati. The acknowledgment is also directed to the School of Health Science and Technology, Param-Ishan and BSL facilities of IIT Guwahati.

Author’s contributions

PS and SRA: Conceptualization, Data curation and analysis, Validation, Writing the original draft. AA: Data analysis, Writing. SSG: Conceptualization, Funding Acquisition, Editing and Supervision.

Disclosure statement

There was no conflict of interest as reported by the authors.

Additional information

Funding

This work was supported by Department of Biotechnology, Ministry of Science and Technology, India.