Wang Youhui, Zhang Wuguang, Peng Min
Tumor Radiotherapy and Chemotherapy Center, Ningbo University Affiliated People's Hospital, No. 251, Baizhang East Road, Ningbo, 315040, Zhejiang, China.
J Mol Histol. 2025 Feb 5;56(2):80. doi: 10.1007/s10735-025-10356-z.
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.
宫颈癌（CC）仍然是全球女性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。本研究调查了细胞分裂周期相关5（CDCA5）在宫颈癌进展中的分子机制和临床意义。我们对宫颈癌组织和正常组织中的CDCA5表达进行了全面分析，将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）进行的功能研究检测了CDCA5调控对肿瘤细胞行为的影响。我们确定E2F1是CDCA5的关键转录调节因子，并使用体内异种移植模型验证了我们的发现。CDCA5在CC组织中显著上调，并与疾病晚期和不良生存结果相关。从机制上讲，SiHa和HeLa细胞中CDCA5的缺失抑制了增殖、迁移和侵袭，而其在CaSki细胞中的过表达增强了这些恶性特性。我们确定E2F1是CDCA5的转录激活因子。重要的是，CDCA5基因敲低显著抑制了裸鼠模型中的肿瘤生长。我们的发现确立了CDCA5作为E2F1调控的关键致癌因子在宫颈癌进展中的作用。CDCA5表达与不良临床结果之间的强相关性表明其在宫颈癌治疗中作为预后生物标志物和治疗靶点的潜力。
