Basic Medical Research Unit, St. Mary's Research Center, 422 Tsubukuhon-Machi, Kurume, Fukuoka, 830-8543, Japan.
Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA.
Sci Rep. 2024 Sep 17;14(1):21701. doi: 10.1038/s41598-024-72174-9.
Y-box binding protein 1 (YBX1) promotes oncogenic transformation and tumor growth. YBX1 plays a role in regulation of cell cycle promotion via upregulation of cell cycle-related genes. In ovarian cancer, YBX1 also promotes tumor growth, but the mechanisms of YBX1 in cell growth and cell cycle in ovarian cancer remain not to be fully understood. Here, we investigated whether YBX1-dependent cancer cell proliferation was specifically associated with expression of cell cycle related genes in ovarian cancer. Protein and mRNA expression levels of YBX1 and cell cycle-related genes in ovarian cancer cell lines and tissues were determined by western blot analysis, immunohistochemical analysis and reverse transcription-quantitative PCR. Cell cycle analysis was performed by flow cytometry. Luciferase assay and Chromatin immunoprecipitation assay were used to investigate a transcriptional function of YBX1. YBX1 silencing induced marked growth suppression in 4 cell lines (group A), moderate suppression in 5 cell lines (group B), and no suppression in 3 cell lines (group C) among 12 ovarian cancer cell lines in culture. The YBX1 silencing induced cell cycle arrest at G/M phase and suppressed expression of cyclin A1 gene in group A and B cell lines, but not in group C cell lines. Cyclin A1 silencing specifically suppressed cell proliferation in group A cell lines and partially in group B cell lines, but not at all in group C cell lines. YBX1 mRNA levels were significantly correlated with cyclin A1 mRNA levels in patients with high-grade serous carcinoma. Augmented YBX1 expression plays a key role in tumor growth promotion in ovarian cancer in its close association with cyclin A1.
Y 盒结合蛋白 1（YBX1）促进致癌转化和肿瘤生长。YBX1 通过上调细胞周期相关基因在细胞周期促进中起作用。在卵巢癌中，YBX1 也促进肿瘤生长，但 YBX1 在卵巢癌细胞生长和细胞周期中的作用机制尚未完全阐明。在这里，我们研究了 YBX1 依赖性癌细胞增殖是否与卵巢癌细胞中细胞周期相关基因的表达特异性相关。通过 Western blot 分析、免疫组织化学分析和逆转录定量 PCR 测定卵巢癌细胞系和组织中的 YBX1 和细胞周期相关基因的蛋白和 mRNA 表达水平。通过流式细胞术进行细胞周期分析。使用荧光素酶测定和染色质免疫沉淀测定来研究 YBX1 的转录功能。在培养的 12 种卵巢癌细胞系中，YBX1 沉默在 4 种细胞系（A 组）中引起明显的生长抑制，在 5 种细胞系（B 组）中引起中度抑制，在 3 种细胞系（C 组）中没有抑制。YBX1 沉默在 A 组和 B 组细胞系中诱导细胞周期停滞在 G2/M 期，并抑制细胞周期蛋白 A1 基因的表达，但在 C 组细胞系中没有抑制。细胞周期蛋白 A1 沉默特异性抑制 A 组细胞系和部分 B 组细胞系的细胞增殖，但对 C 组细胞系完全没有抑制。在高级别浆液性癌患者中，YBX1 mRNA 水平与 cyclin A1 mRNA 水平显著相关。增强的 YBX1 表达与其与 cyclin A1 的密切关联在卵巢癌的肿瘤生长促进中起着关键作用。
