Department of Dermatology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Cell Death Differ. 2011 Jul;18(7):1220-30. doi: 10.1038/cdd.2010.188. Epub 2011 Jan 28.
Head and neck squamous cell carcinoma (HNSCC) cells exposed to cisplatin (CIS) displayed a dramatic ATM-dependent phosphorylation of ΔNp63α that leads to the transcriptional regulation of downstream mRNAs. Here, we report that phospho (p)-ΔNp63α transcriptionally deregulates miRNA expression after CIS treatment. Several p-ΔNp63α-dependent microRNA species (miRNAs) were deregulated in HNSCC cells upon CIS exposure, including miR-181a, miR-519a, and miR-374a (downregulated) and miR-630 (upregulated). Deregulation of miRNA expression led to subsequent modulation of mRNA expression of several targets (TP53-S46, HIPK2, ATM, CDKN1A and 1B, CASP3, PARP1 and 2, DDIT1 and 4, BCL2 and BCL2L2, TP73, YES1, and YAP1) that are involved in the apoptotic process. Our data support the notion that miRNAs are critical downstream targets of p-ΔNp63α and mediate key pathways implicated in the response of cancer cells to chemotherapeutic drugs.
头颈部鳞状细胞癌（HNSCC）细胞在顺铂（cisplatin，CIS）作用下表现出明显的 ATM 依赖性 ΔNp63α磷酸化，从而导致下游 mRNA 的转录调控。在这里，我们报告了磷酸化（p）-ΔNp63α 在 CIS 处理后转录调控 miRNA 表达。在 CIS 暴露后，HNSCC 细胞中几种 p-ΔNp63α 依赖性 miRNA 物种（miRNAs）被下调，包括 miR-181a、miR-519a 和 miR-374a（下调）以及 miR-630（上调）。miRNA 表达的失调导致了几个靶基因（TP53-S46、HIPK2、ATM、CDKN1A 和 1B、CASP3、PARP1 和 2、DDIT1 和 4、BCL2 和 BCL2L2、TP73、YES1 和 YAP1）mRNA 表达的后续调节，这些靶基因参与细胞凋亡过程。我们的数据支持了这样一种观点，即 miRNA 是 p-ΔNp63α 的关键下游靶标，并介导了与癌细胞对化疗药物反应相关的关键途径。
