Cintra Ricardo Cesar, Céspedes Andrés Galindo, Conceição Mércia Patrícia Ferreira, Oliveira Maiza Vitoria Aguiar Silva, Buron Alessandro, Rodrigues das Neves Deisiane, Moraes Fabio Alves, Gamarra Olinda Maria, Rodrigues de Bastos Daniel
Department of Oncology, Universidade de São Paulo, São Paulo 71.961-540, Brazil.
Clinical Pathology Service, Almanzor Aguinaga Asenjo National Hospital, Chiclayo 14001, Peru.
Precis Clin Med. 2024 Jul 24;7(3):pbae016. doi: 10.1093/pcmedi/pbae016. eCollection 2024 Sep.
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).
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.
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.
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.
富含半胱氨酸的分泌蛋白3（CRISP3）在包括宫颈癌（CC）在内的多种癌症研究中成为一种潜在的生物标志物。本研究旨在分析CC患者和CC细胞系中CRISP3在经表观遗传药物曲古抑菌素A（TSA）和5-氮杂-2'-脱氧胞苷（5-aza）处理后的表达模式。
利用在GSE63514中鉴定出的差异表达基因构建蛋白质-蛋白质相互作用网络。选择CRISP3进行后续分析。我们利用来自TCGA和GENT2项目的数据评估CRISP3的表达谱和临床行为。此外，我们进行细胞培养实验以分析CRISP3在细胞中的表达谱。
在鳞状细胞癌（SCC）和人乳头瘤病毒（HPV）16+中观察到CRISP3水平较低，并且与较差的总生存期（OS）相关。分析了MIR-1229-3p，其高表达与较差的预后结果相关。在源自CC的细胞系中，我们在SiHa中观察到CRISP3水平较低，其次是SW756、C33A、HeLa，而在CaSki中水平较高。所有细胞均用TSA、5-aza或两者处理。在所有细胞系中，用TSA处理导致CRISP3转录增加。
我们发现CC中CRISP3显著下调，特别是在HPV16感染和SCC病例中，这与较差的OS相关。初步研究结果表明，用TSA和5-aza进行表观遗传治疗可能调节CRISP3表达，值得进一步研究以阐明其调控机制及其作为预后生物标志物的潜力。
