The TP63 gene, which encodes the p63 protein, is involved in multiple biological processes, including embryonic development and tumorigenesis. ΔNp63α, the predominant isoform of p63 in epithelial cells, acts as an oncogene in early‐stage tumors, but paradoxically acts as a potent antimetastatic factor in advanced cancers. Here, we report that ΔNp63α is a direct target of hsa‐miR‐522 (miR‐522). Induced expression of miR‐522 reduced the levels of ΔNp63α, predisposing breast epithelial cells to a loss of epithelial and acquisition of mesenchymal morphology, resulting in accelerated collective and single‐cell migration. Restoration of ΔNp63α repressed miR‐522‐induced migration. Interestingly, overexpression of miR‐522 did not affect breast epithelial cell proliferation, suggesting that miR‐522 acts specifically through ΔNp63α in this context. Furthermore, expression of miR‐522‐3p and p63 was negatively correlated in human cancer samples. Thus, miR‐522 might be a causative factor for breast tumorigenesis and cancer metastasis. In summary, our results reveal a novel miR‐522/p63 axis in cell migration and thus suggest a potential strategy for therapeutic treatment of cancer metastasis.

中文翻译：

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miR-522靶向ΔNp63α促进乳腺上皮细胞的迁移

TP63 _编码 p63 蛋白的基因参与多个生物学过程，包括胚胎发育和肿瘤发生。ΔNp63α 是上皮细胞中 p63 的主要同种型，在早期肿瘤中充当癌基因，但在晚期癌症中却充当有效的抗转移因子。在这里，我们报告 ΔNp63α 是 hsa-miR-522 (miR-522) 的直接靶标。miR-522 的诱导表达降低了 ΔNp63α 的水平，使乳腺上皮细胞易发生上皮细胞丧失和间充质形态的获得，从而加速集体和单细胞迁移。ΔNp63α 的恢复抑制了 miR-522 诱导的迁移。有趣的是，miR-522 的过表达并不影响乳腺上皮细胞的增殖，这表明 miR-522 在这种情况下通过 ΔNp63α 特异性发挥作用。此外，miR-522-3p 和 p63 的表达在人类癌症样本中呈负相关。因此，miR-522可能是乳腺肿瘤发生和癌症转移的一个致病因素。总之，我们的研究结果揭示了细胞迁移中新的 miR-522/p63 轴，因此提出了治疗癌症转移的潜在策略。