KLF5-mediated CDCA5 expression promotes tumor development and progression of epithelial ovarian carcinoma

• Published in: Experimental cell research Vol. 429; no. 1; p. 113645
• Main Authors: Chen, Xiaohong, Zhou, Meiying, Ma, Shouye, Wu, Huifang, Cai, Hui
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.08.2023
• Subjects: Adaptor Proteins, Signal Transducing - metabolism; Carcinoma, Ovarian Epithelial - metabolism; Cell cycle; Cell Cycle - genetics; Cell Cycle Proteins - genetics; Cell Cycle Proteins - metabolism; Cell division cycle associated 5; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; Epithelial ovarian cancer; Female; Gene Expression Regulation, Neoplastic - genetics; Humans; Kruppel-Like Transcription Factors - genetics; Kruppel-Like Transcription Factors - metabolism; Krüppel-like factor 5; Ovarian Neoplasms - pathology; P53 signal pathway; Proliferation; Tumor Suppressor Protein p53 - genetics; Tumor Suppressor Protein p53 - metabolism; Krüppel-like factor 5; P53 signal pathway; Proliferation; Epithelial ovarian cancer; Cell division cycle associated 5; Cell cycle
• ISSN: 0014-4827; 1090-2422
• DOI: 10.1016/j.yexcr.2023.113645

Cell division cycle associated 5 (CDCA5) is correlated with the development and progression of many malignant tumors. However, little is known about its role in epithelial ovarian cancer (EOC) progression. In this study, the clinical value, biological function and underlying mechanisms of CDCA5 in EOC were evaluated. CDCA5 mRNA and protein levels were substantially upregulated in EOC and had a significant positive correlation with adverse clinicopathological characteristics and a poor prognosis. CDCA5 facilitated proliferation, invasion, and metastasis and disrupted mitochondrial-mediated endogenous apoptosis by activating the cell cycle pathway and inhibiting the P53 pathway in EOC cells. Conversely, knockdown of CDCA5 expression blocked the malignant activities of EOC cells and suppressed the growth of xenograft tumors in vivo. Mechanistically, the transcription factor KLF5 bound to a specific site in the CDCA5 promoter and promoted CDCA5 expression. Moreover, KLF5 overexpression rescued the negative regulation of inhibited CDCA5 expression on EOC cell proliferation. In conclusion, our findings revealed that CDCA5 promoted tumor progression of EOC via the KLF5/CDCA5/cell cycle and P53 axes, which might provide new insights into the roles of CDCA5 in EOC. [Display omitted] •CDCA5 is highly expressed in epithelial ovarian cancer and is associated with poor prognosis.•Interfering with the expression of CDCA5 makes cells stagnate in G2/M phase and promotes cell apoptosis.•Overexpression of CDCA5 promotes tumor progression by activating cell cycle and inhibiting P54 pathway.•KLF5 mediated CDCA5 expression promotes malignant activity of tumor cells.