许多恶性肿瘤的一个特点是分化不全的（未成熟的）细胞，与癌症起源的正常细胞几乎没有相似之处。肿瘤分化不全细胞具有更高的耐药化疗和放疗的能力，并能诱发肿瘤复发。诱导癌细胞分化将消除其自我更新和浸润能力，并可与当前的标准治疗方法结合使用，尤其是在分化差和侵袭性肿瘤（预后最差的）中。然而，分化治疗仍处于早期阶段，并且实体肿瘤异质性的内在复杂性要求创新的方法，以便有效地在临床中应用。我们在这里证明，miR-203，一种对多能干细胞（ESCs和iPSCs）分化具有强大驱动作用的微小RNA，促进乳腺腺体肿瘤细胞的分化。结合小鼠体内实验方法和小鼠和人源三维器官培养，我们报告了miR-203如何影响乳腺癌细胞的自我更新能力、可塑性和分化潜能，并阻止肿瘤细胞的体内生长。我们的研究为基于分化的抗肿瘤治疗方法提供了新的认识，并提出miR-203作为直接对抗癌细胞的肿瘤维持和再生能力的有希望的工具。© 2023. BioMed Central Ltd.，属于Springer Nature的一部分。

A hallmark of many malignant tumors is dedifferentiated (immature) cells bearing slight or no resemblance to the normal cells from which the cancer originated. Tumor dedifferentiated cells exhibit a higher capacity to survive to chemo and radiotherapies and have the ability to incite tumor relapse. Inducing cancer cell differentiation would abolish their self-renewal and invasive capacity and could be combined with the current standard of care, especially in poorly differentiated and aggressive tumors (with worst prognosis). However, differentiation therapy is still in its early stages and the intrinsic complexity of solid tumor heterogeneity demands innovative approaches in order to be efficiently translated into the clinic. We demonstrate here that microRNA 203, a potent driver of differentiation in pluripotent stem cells (ESCs and iPSCs), promotes the differentiation of mammary gland tumor cells. Combining mouse in vivo approaches and both mouse and human-derived tridimensional organoid cultures, we report that miR-203 influences the self-renewal capacity, plasticity and differentiation potential of breast cancer cells and prevents tumor cell growth in vivo. Our work sheds light on differentiation-based antitumor therapies and offers miR-203 as a promising tool for directly confronting the tumor-maintaining and regeneration capability of cancer cells.© 2023. BioMed Central Ltd., part of Springer Nature.