三阴性乳腺癌（TNBC）缺乏激素和HER2受体的表达，恶性程度高，没有有效的治疗靶点。在TNBC中，癌症干细胞样细胞（CSC）群体被认为是治疗耐药的主要原因。因此，针对这一人群的治疗目标可以显着提高患者的生存率。在这里，我们鉴定出 RNA 结合蛋白 ZCCHC24 在间质样 TNBC 群体中富集。 ZCCHC24通过直接结合mRNA中的顺式元件“UGUWHWWA”来促进一组与致瘤性和治疗耐药性相关的基因的表达，从而稳定它们。 ZCCHC24 靶标之一 ZEB1 是一种转录因子，可促进癌症干性基因的表达并交互诱导 ZCCHC24 表达。 siRNA 敲低 ZCCHC24 显示出治疗效果，并减少了 TNBC 患者来源的异种移植物中的间充质样细胞群。 ZCCHC24 敲除与 BET 抑制剂 JQ1 一起抑制 TNBC 患者来源的异种移植物中的肿瘤生长也具有累加效应。© 2024。作者。

Triple-negative breast cancer (TNBC) lacks the expression of hormone and HER2 receptors and is highly malignant with no effective therapeutic targets. In TNBC, the cancer stem-like cell (CSC) population is considered to be the main cause of resistance to treatment. Thus, the therapeutic targeting of this population could substantially improve patient survival. Here, we identify the RNA-binding protein ZCCHC24 as enriched in the mesenchymal-like TNBC population. ZCCHC24 promotes the expression of a set of genes related to tumorigenicity and treatment resistance by directly binding to the cis-element "UGUWHWWA" in their mRNAs, thereby stabilizing them. One of the ZCCHC24 targets, ZEB1, is a transcription factor that promotes the expression of cancer stemness genes and reciprocally induces ZCCHC24 expression. ZCCHC24 knockdown by siRNAs shows a therapeutic effect and reduces the mesenchymal-like cell population in TNBC patient-derived xenografts. ZCCHC24 knockdown also has additive effects with the BET inhibitor JQ1 in suppressing tumor growth in TNBC patient-derived xenografts.© 2024. The Author(s).