Cancer stem-like cell (CSC) is thought to be responsible for ovarian cancer recurrence. CD24 serves as a CSC marker for ovarian cancer and regulates the expression of miRNAs, which are regulators of CSC phenotypes. Therefore, CD24-regulated miRNAs may play roles in manifesting the CSC phenotypes in ovarian cancer cells. Our miRNA transcriptome analysis showed that 94 miRNAs were up or down-regulated in a CD24-high clone from an ovarian cancer patient compared to a CD24-low one. The CD24-dependent expression trend of the top 7 upregulated miRNAs (miR-199a-3p, 34c, 199a-5p, 130a, 301a, 214, 34b*) was confirmed in other 8 clones (4 clones for each group). CD24 overexpression upregulated the expression of miR-199a-3p, 34c, 199a-5p, 130a, 301a, 214, and 34b* in TOV112D (CD24-low) cells compared to the control, while CD24 knockdown downregulated the expression of miR-199a-3p, 199a-5p, 130a, 301a, and 34b* in OV90 (CD24-high) cells. miR-130a and 301a targeted CDK19, which induced a cellular quiescence-like state (increased G0/G1 phase cell population, decreased cell proliferation, decreased colony formation, and decreased RNA synthesis) and resistance to platinum-based chemotherapeutic agents. CD24 regulated the expression of miR-130a and 301a via STAT4 and YY1 phosphorylation mediated by Src and FAK. miR-130a and 301a were positively correlated in expression with CD24 in ovarian cancer patient tissues and negatively correlated with CDK19. Our results showed that CD24 expression may induce a cellular quiescence-like state and resistance to platinum-based chemotherapeutic agents in ovarian cancer via miR-130a and 301a upregulation. CD24-miR-130a/301a-CDK19 signaling axis could be a prognostic marker for or a potential therapeutic target against ovarian cancer recurrence.

癌症干细胞样细胞（CSC）被认为是导致卵巢癌复发的原因。 CD24 作为卵巢癌的 CSC 标志物，调节 miRNA 的表达，而 miRNA 是 CSC 表型的调节因子。因此，CD24调节的miRNA可能在卵巢癌细胞中CSC表型的表现中发挥作用。我们的 miRNA 转录组分析表明，与 CD24 低克隆相比，卵巢癌患者的 CD24 高克隆中有 94 个 miRNA 上调或下调。在其他 8 个克隆（每组 4 个克隆）中证实了前 7 个上调 miRNA（miR-199a-3p、34c、199a-5p、130a、301a、214、34b*）的 CD24 依赖性表达趋势。与对照相比，TOV112D (CD24-low) 细胞中 CD24 过表达上调了 miR-199a-3p、34c、199a-5p、130a、301a、214 和 34b* 的表达，而 CD24 敲低则下调了 miR-199a 的表达OV90（CD24 高）细胞中的 -3p、199a-5p、130a、301a 和 34b*。 miR-130a和301a靶向CDK19，CDK19诱导细胞类静止状态（G0/G1期细胞数量增加、细胞增殖减少、集落形成减少和RNA合成减少）和对铂类化疗药物的耐药性。 CD24 通过 Src 和 FAK 介导的 STAT4 和 YY1 磷酸化调节 miR-130a 和 301a 的表达。卵巢癌患者组织中miR-130a、301a的表达量与CD24呈正相关,与CDK19呈负相关。我们的结果表明，CD24 表达可能通过 miR-130a 和 301a 上调诱导卵巢癌中细胞的类静止状态和对铂类化疗药物的耐药性。 CD24-miR-130a/301a-CDK19 信号轴可能是卵巢癌复发的预后标志物或潜在的治疗靶点。