IF 2.9 4区 生物学 Q3 CELL BIOLOGY
Youhui Wang, Wuguang Zhang, Min Peng
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引用次数: 0

摘要

宫颈癌(CC)仍然是全球妇女癌症相关死亡的主要原因,这凸显了对新型治疗策略的迫切需求。本研究探讨了细胞分裂周期相关 5(CDCA5)在宫颈癌进展过程中的分子机制和临床意义。我们对 CDCA5 在宫颈癌和正常组织中的表达进行了全面分析,并将其表达水平与临床病理特征和患者预后相关联。使用 CC 细胞系(SiHa、HeLa 和 CaSki)进行的功能研究检验了 CDCA5 操作对肿瘤细胞行为的影响。我们发现 E2F1 是 CDCA5 的关键转录调节因子,并利用体内异种移植模型验证了我们的发现。CDCA5 在 CC 组织中明显上调,并与疾病晚期和不良生存结果相关。从机理上讲,CDCA5在SiHa和HeLa细胞中的缺失抑制了细胞的增殖、迁移和侵袭,而在CaSki细胞中的过表达则增强了这些恶性特性。我们发现 E2F1 是 CDCA5 的转录激活因子。重要的是,敲除 CDCA5 能显著抑制裸鼠模型中肿瘤的生长。我们的研究结果确立了 CDCA5 在宫颈癌进展过程中是一个关键的 E2F1 调控致癌因子。CDCA5 的表达与不良临床预后之间的强相关性表明,它有可能成为宫颈癌治疗中的预后生物标志物和治疗靶点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
E2F1-Dependent CDCA5 overexpression drives cervical cancer progression and correlates with poor prognosis

Cervical cancer (CC) remains a leading cause of cancer-related mortality in women worldwide, highlighting the urgent need for novel therapeutic strategies. This study investigates the molecular mechanisms and clinical significance of Cell Division Cycle Associated 5 (CDCA5) in cervical cancer progression. We performed comprehensive analyses of CDCA5 expression in cervical cancer and normal tissues, correlating expression levels with clinicopathological features and patient outcomes. Functional studies using CC cell lines (SiHa, HeLa, and CaSki) examined the effects of CDCA5 manipulation on tumor cell behavior. We identified E2F1 as a key transcriptional regulator of CDCA5 and validated our findings using in vivo xenograft models. CDCA5 was significantly upregulated in CC tissues and correlated with advanced disease stages and poor survival outcomes. Mechanistically, CDCA5 depletion in SiHa and HeLa cells suppressed proliferation, migration, and invasion, while its overexpression in CaSki cells enhanced these malignant properties. We identified E2F1 as a transcriptional activator of CDCA5. Importantly, CDCA5 knockdown significantly inhibited tumor growth in nude mouse models. Our findings establish CDCA5 as a critical E2F1-regulated oncogenic factor in cervical cancer progression. The strong correlation between CDCA5 expression and poor clinical outcomes suggests its potential as both a prognostic biomarker and therapeutic target in cervical cancer treatment.

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来源期刊
Journal of Molecular Histology
Journal of Molecular Histology 生物-细胞生物学
CiteScore
5.90
自引率
0.00%
发文量
68
审稿时长
1 months
期刊介绍: The Journal of Molecular Histology publishes results of original research on the localization and expression of molecules in animal cells, tissues and organs. Coverage includes studies describing novel cellular or ultrastructural distributions of molecules which provide insight into biochemical or physiological function, development, histologic structure and disease processes. Major research themes of particular interest include: - Cell-Cell and Cell-Matrix Interactions; - Connective Tissues; - Development and Disease; - Neuroscience. Please note that the Journal of Molecular Histology does not consider manuscripts dealing with the application of immunological or other probes on non-standard laboratory animal models unless the results are clearly of significant and general biological importance. The Journal of Molecular Histology publishes full-length original research papers, review articles, short communications and letters to the editors. All manuscripts are typically reviewed by two independent referees. The Journal of Molecular Histology is a continuation of The Histochemical Journal.
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