| RRC ID |
69740
|
| 著者 |
Sawai Y, Kasamatsu A, Nakashima D, Fushimi K, Kasama H, Iyoda M, Kouzu Y, Shiiba M, Tanzawa H, Uzawa K.
|
| タイトル |
Critical role of deoxynucleotidyl transferase terminal interacting protein 1 in oral cancer.
|
| ジャーナル |
Lab Invest
|
| Abstract |
Deoxynucleotidyl transferase terminal interacting protein 1 (DNTTIP1) forms a complex with histone deacetylase (HDAC); however, the relevance of DNTTIP1 in cancer remains unknown. The aim of this study was to examine DNTTIP1 expression and its functional mechanisms in oral squamous cell carcinomas (OSCCs). DNTTIP1 expression was analyzed by quantitative reverse transcriptase-polymerase chain reaction, immunoblotting analysis, and immunohistochemistry. The expression of DNTTIP1 was upregulated significantly in vitro and in vivo, and in patients with OSCC in whom DNTTIP1 was overexpressed and the expression level was correlated significantly (P < 0.05) with tumoral growth. DNTTIP1 knockdown (siDNTTIP1) cells showed depressed cellular proliferation by cell-cycle arrest at the G1 phase with high acetylation of p53 and upregulation of p21Cip1. Moreover, resveratrol, a HDAC inhibitor, controlled not only acetylated p53 status but also DNTTIP1 expression, leading to a similar phenotype of siDNTTIP1 cells. A marked (P < 0.05) reduction of tumoral growth in mouse xenograft models was observed with lower DNTTIP1 expression under the presence of this chemical reagent. Taken together, our results suggested that DNTTIP1-HDAC interaction promotes tumoral growth through deacetylation of p53 and that DNTTIP1 might be a critical therapeutic target in OSCCs.
|
| 巻・号 |
98(8)
|
| ページ |
980-988
|
| 公開日 |
2018-8-1
|
| DOI |
10.1038/s41374-018-0070-3
|
| PII |
10.1038/s41374-018-0070-3
|
| PMID |
29855544
|
| MeSH |
Aged
Animals
Antineoplastic Agents, Phytogenic / pharmacology
Carcinoma, Squamous Cell / drug therapy
Carcinoma, Squamous Cell / genetics*
Carcinoma, Squamous Cell / metabolism
Carrier Proteins / genetics*
Carrier Proteins / metabolism
Cell Cycle Checkpoints / drug effects
Cell Cycle Checkpoints / genetics
Cell Line, Tumor
Cell Proliferation / drug effects
Cell Proliferation / genetics*
DNA-Binding Proteins
Female
Gene Expression Regulation, Neoplastic / drug effects
Humans
Male
Mice, Inbred BALB C
Mice, Nude
Mouth Neoplasms / drug therapy
Mouth Neoplasms / genetics*
Mouth Neoplasms / metabolism
Nuclear Proteins / genetics*
Nuclear Proteins / metabolism
RNA Interference
Resveratrol / pharmacology
Transcription Factors
Xenograft Model Antitumor Assays / methods
|
| IF |
4.197
|
| リソース情報 |
| ヒト・動物細胞 |
HSC-4(RCB1902)
HO-1-u-1(RCB2102)
SAS(RCB1974)
Sa3(RCB0980)
Ca9-22(RCB1976)
HSC-3(RCB1975)
HSC-2(RCB1945) |
