The oncogenic role of circPVT1 in head and neck squamous cell carcinoma is mediated through the mutant p53/YAP/TEAD transcription-competent complex

被引:254
作者
Verduci, Lorena [1 ]
Ferraiuolo, Maria [1 ,2 ]
Sacconi, Andrea [1 ]
Ganci, Federica [1 ]
Vitale, Jlenia [1 ]
Colombo, Teresa [3 ]
Paci, Paola [4 ]
Strano, Sabrina [2 ]
Macino, Giuseppe [5 ]
Rajewsky, Nikolaus [6 ]
Blandino, Giovanni [1 ]
机构
[1] Italian Natl Canc Inst, Oncogen & Epigenet Unit, I-00144 Rome, Italy
[2] Italian Natl Canc Inst, Mol Chemoprevent Unit, I-00144 Rome, Italy
[3] CNR, Inst Comp Applicat Mauro Picone, I-00185 Rome, Italy
[4] CNR, Inst Syst Anal & Comp Sci Antonio Ruberti, I-00185 Rome, Italy
[5] Univ Roma La Sapienza, Dept Cellular Biotechnol & Hematol, I-00161 Rome, Italy
[6] Max Delbruck Ctr Mol Med, Berlin Inst Med Syst Biol, Syst Biol Gene Regulatory Elements, D-13125 Berlin, Germany
关键词
circPVT1; mut-p53; PVT1; YAP; TEAD; miR-497-5p; HNSCC; CIRCULAR RNA; MUTATIONAL LANDSCAPE; CANCER; GROWTH; P53; EXPRESSION; BIOMARKER; BIOGENESIS; OVARIAN;
D O I
10.1186/s13059-017-1368-y
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 [微生物学]; 090105 [作物生产系统与生态工程];
摘要
Background: Circular RNAs are a class of endogenous RNAs with various functions in eukaryotic cells. Worthy of note, circular RNAs play a critical role in cancer. Currently, nothing is known about their role in head and neck squamous cell carcinoma (HNSCC). The identification of circular RNAs in HNSCC might become useful for diagnostic and therapeutic strategies in HNSCC. Results: Using samples from 115 HNSCC patients, we find that circPVT1 is over-expressed in tumors compared to matched non-tumoral tissues, with particular enrichment in patients with TP53 mutations. circPVT1 up-and down-regulation determine, respectively, an increase and a reduction of the malignant phenotype in HNSCC cell lines. We show that circPVT1 expression is transcriptionally enhanced by the mut-p53/YAP/TEAD complex. circPVT1 acts as an oncogene modulating the expression of miR-497-5p and genes involved in the control of cell proliferation. Conclusions: This study shows the oncogenic role of circPVT1 in HNSCC, extending current knowledge about the role of circular RNAs in cancer.
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页数:24
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