TY - JOUR
T1 - Phospho-ΔNp63α is a key regulator of the cisplatin-induced microRNAome in cancer cells
AU - Huang, Y.
AU - Chuang, A.
AU - Hao, H.
AU - Talbot, C.
AU - Sen, T.
AU - Trink, B.
AU - Sidransky, D.
AU - Ratovitski, E.
N1 - Funding Information:
Acknowledgements. This work was supported in part by NIH grant 5R01DE13561 (DS, ER and BT).
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
KW - DICER1
KW - cisplatin
KW - microRNA
KW - p63
KW - squamous cell carcinomas
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U2 - 10.1038/cdd.2010.188
DO - 10.1038/cdd.2010.188
M3 - Article
C2 - 21274007
AN - SCOPUS:79958831395
SN - 1350-9047
VL - 18
SP - 1220
EP - 1230
JO - Cell Death and Differentiation
JF - Cell Death and Differentiation
IS - 7
ER -