Analysing the relevance of TGF-β and its regulators in cervical cancer to identify therapeutic and diagnostic markers

Jayapradha Gnanagurusamy; Sneha Krishnamoorthy; Bharathi Muruganatham; Nagarajan Selvamurugan; Sridhar Muthusami

doi:10.1016/j.gene.2024.149166

Analysing the relevance of TGF-β and its regulators in cervical cancer to identify therapeutic and diagnostic markers

Gene. 2025 Feb 20:938:149166. doi: 10.1016/j.gene.2024.149166. Epub 2024 Dec 18.

Authors

Jayapradha Gnanagurusamy¹, Sneha Krishnamoorthy¹, Bharathi Muruganatham², Nagarajan Selvamurugan³, Sridhar Muthusami⁴

Affiliations

¹ Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India; Centre for Cancer Research, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India.
² Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India; Centre for Bioinformatics, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India.
³ Department of Biotechnology, School of Bioengineering, SRM Institute of Science and Technology, Kattankulathur Chennai 603 203 Tamil Nadu, India.
⁴ Department of Biochemistry, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India; Centre for Cancer Research, Karpagam Academy of Higher Education, Coimbatore 641021, Tamil Nadu, India. Electronic address: [email protected].

PMID: 39701195
DOI: 10.1016/j.gene.2024.149166

Abstract

The role of transforming growth factor-beta (TGF-β) is dual, such that, it inhibits tumor development in initial stage and promotes metastasis in later stage. The present study is aimed to analyse the relevance of different types of TGF-β and their receptors on the overall survival (OS) and TGF-β driven gene expression in individuals with cervical cancer (CC) using ONCODB and GEPIA databases. The in-silico gene expression analysis showed, TGF-β1 and TGFβR2 are upregulated in cells infected with human papilloma virus (HPV)16, whereas, TGF-β2, TGFβR1 and TGFβR3 expression were downregulated. In HPV 18 infected cells, TGF-β1, TGF-β2 and TGFβR1 were downregulated, meanwhile, TGF-β3, TGFβR2 and TGFβR3 were upregulated. OS analysis of CC patients with different TGF-β expression revealed that, TGF-β1, TGF-β2, TGF-β3 and TGFβR2 were associated with reduced survival rate. Further, we identified four microRNAs (miRNAs) (hsa-miR-21-5p, hsa-miR-29b-3p, hsa-miR-101-3p and hsa-miR-130a-3p) interacted favorably with TGF-β in HPV 16 and 18 positive samples using MIENTURNET. This present review further emphasizes that, targeting TGF-β could be a novel and futuristic approach for CC management and therapeutics.

Keywords: Cervical Cancer; Exosomes; TGF-β; TGF-β Receptors; miRNA.

Publication types

Review

MeSH terms

Biomarkers, Tumor* / genetics
Biomarkers, Tumor* / metabolism
Female
Gene Expression Regulation, Neoplastic*
Human papillomavirus 16 / genetics
Human papillomavirus 18 / genetics
Humans
MicroRNAs* / genetics
MicroRNAs* / metabolism
Papillomavirus Infections / genetics
Papillomavirus Infections / virology
Receptor, Transforming Growth Factor-beta Type I / genetics
Receptor, Transforming Growth Factor-beta Type I / metabolism
Receptor, Transforming Growth Factor-beta Type II / genetics
Receptor, Transforming Growth Factor-beta Type II / metabolism
Receptors, Transforming Growth Factor beta / genetics
Receptors, Transforming Growth Factor beta / metabolism
Transforming Growth Factor beta / genetics
Transforming Growth Factor beta / metabolism
Transforming Growth Factor beta1 / genetics
Transforming Growth Factor beta1 / metabolism
Transforming Growth Factor beta2 / genetics
Transforming Growth Factor beta2 / metabolism
Transforming Growth Factor beta3 / genetics
Transforming Growth Factor beta3 / metabolism
Uterine Cervical Neoplasms* / diagnosis
Uterine Cervical Neoplasms* / genetics
Uterine Cervical Neoplasms* / metabolism
Uterine Cervical Neoplasms* / pathology

Substances

MicroRNAs
Biomarkers, Tumor
Transforming Growth Factor beta2
Receptors, Transforming Growth Factor beta
Transforming Growth Factor beta
Transforming Growth Factor beta1
TGFBR2 protein, human
Receptor, Transforming Growth Factor-beta Type II
MIRN29a microRNA, human
MIRN21 microRNA, human
Receptor, Transforming Growth Factor-beta Type I
TGFB1 protein, human
TGFB2 protein, human
Transforming Growth Factor beta3
TGFB3 protein, human