Computational insights into CRISP3 downregulation in cervical cancer and its cervical lineages pattern

Abstract

Background: Cysteine-rich secretory protein 3 (CRISP3) emerges as a potential biomarker in the study of many cancers, including cervical cancer (CC). This study aimed to analyze the expression pattern of CRISP3 in CC patients and CC cell lineages, following treatment with the epigenetic drugs: trichostatin A (TSA) and 5-aza-2'-deoxycytidine (5-aza).

Methods: The differentially expressed genes identified in GSE63514 were used to construct a protein-protein interaction network. CRISP3 was selected for subsequent analyses. We utilized data from the TCGA and GENT2 projects to evaluate the expression profile and clinical behavior of CRISP3. Additionally, we conducted cell culture experiments to analyze the expression profile of CRISP3 in cells.

Results: Low levels of CRISP3 were observed in squamous cell carcinoma (SCC) and human papillomavirus (HPV)16+, along with being associated with worse overall survival (OS). MIR-1229-3p was analyzed, and its high expression was associated with worse prognostic outcomes. In CC-derived cell lines, we observed low levels of CRISP3 in SiHa, followed by SW756, C33A, HeLa, and higher levels in CaSki. All cells were treated with TSA, 5-aza, or both. In all cell lines, treatment with TSA resulted in increased transcription of CRISP3.

Conclusion: We identified a significant downregulation of CRISP3 in CC, particularly in cases with HPV16 infection and SCC, which was associated with poorer OS. Preliminary findings suggest that epigenetic treatments with TSA and 5-aza may modulate CRISP3 expression, warranting further research to elucidate its regulatory mechanisms and potential as a prognostic biomarker.

Keywords

cervical cancer / uterine cervical carcinoma / CRISP3 / biomarkers in cancer / prognosis

Acknowledgements

We sincerely thank Prof. Dr Luisa Villa for graciously providing access to her laboratory facilities, which made the execution of this study possible.

Author contributions

RCC: Formal Analysis, Investigation, Methodology, Writing - review & editing. A.G.C.: Formal Analysis, Investigation, Methodology, Writing - original draft. M.P.F.C., A.B., M.V.A.S.O., D.R.N., F.A.M. and O.M.G.: Investigation, Writing - original draft. D.R.B.: Conceptualization, Data curation, Formal Analysis, Funding acquisition, Investigation, Methodology, Project administration, Supervision, Writing - review & editing.

Supplementary data

Supplementary data is available at PCMEDI online.

Conflict of interest

The authors declare that there is no conflict of interest.

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