In silico analysis to identify novel ceRNA regulatory axes associated with gallbladder cancer

Neeraj Saklani; Varnit Chauhan; Javed Akhtar; Santosh Kumar Upadhyay; Ravi Sirdeshmukh; Poonam Gautam

doi:10.3389/fgene.2023.1107614

In silico analysis to identify novel ceRNA regulatory axes associated with gallbladder cancer

Front Genet. 2023 Feb 16:14:1107614. doi: 10.3389/fgene.2023.1107614. eCollection 2023.

Authors

Neeraj Saklani¹, Varnit Chauhan², Javed Akhtar¹, Santosh Kumar Upadhyay³, Ravi Sirdeshmukh^{4

5}, Poonam Gautam¹

Affiliations

¹ Laboratory of Molecular Oncology, ICMR- National Institute of Pathology, New Delhi, India.
² Department of Biotechnology, Gautam Buddha University, Greater Noida, Uttar Pradesh, India.
³ Department of Biotechnology, Sir J. C. Bose Technical Campus, Bhimtal, Kumaun University, Nainital, Uttarakhand, India.
⁴ Manipal Academy of Higher Education (MAHE), Manipal, India.
⁵ Institute of Bioinformatics, International Tech Park, Bangalore, India.

Abstract

Competitive endogenous RNA (ceRNA) networks are reported to play a crucial role in regulating cancer-associated genes. Identification of novel ceRNA networks in gallbladder cancer (GBC) may improve the understanding of its pathogenesis and might yield useful leads on potential therapeutic targets for GBC. For this, a literature survey was done to identify differentially expressed lncRNAs (DELs), miRNAs (DEMs), mRNAs (DEGs) and proteins (DEPs) in GBC. Ingenuity pathway analysis (IPA) using DEMs, DEGs and DEPs in GBC identified 242 experimentally observed miRNA-mRNA interactions with 183 miRNA targets, of these 9 (CDX2, MTDH, TAGLN, TOP2A, TSPAN8, EZH2, TAGLN2, LMNB1, and PTMA) were reported at both mRNA and protein levels. Pathway analysis of 183 targets revealed p53 signaling among the top pathway. Protein-protein interaction (PPI) analysis of 183 targets using the STRING database and cytoHubba plug-in of Cytoscape software revealed 5 hub molecules, of which 3 of them (TP53, CCND1 and CTNNB1) were associated with the p53 signaling pathway. Further, using Diana tools and Cytoscape software, novel lncRNA-miRNA-mRNA networks regulating the expression of TP53, CCND1, CTNNB1, CDX2, MTDH, TOP2A, TSPAN8, EZH2, TAGLN2, LMNB1, and PTMA were constructed. These regulatory networks may be experimentally validated in GBC and explored for therapeutic applications.

Keywords: P53 signaling pathway; ceRNA regulatory network; gallbladder cancer; lncRNA-miRNA-mRNA regulatory axes; therapeutic applications.

Grants and funding

The work reported here was financially supported by the Indian Council of Medical Research (ICMR) (Project ID - 2020-0109), Govt. of India, New Delhi. NS has been working as Project Junior Research Fellow (JRF) under the ICMR project. JA is a Ph.D. student registered at Jamia Hamdard, New Delhi and a recipient of Senior Research Fellowship (SRF) from ICMR-National Institute of Pathology (NIP), Govt. of India.