論文 - 詳細
| RRC ID | 59845 |
|---|---|
| 著者 | Shirai YT, Mizutani A, Nishijima S, Horie M, Kikuguchi C, Elisseeva O, Yamamoto T. |
| タイトル | CNOT3 targets negative cell cycle regulators in non-small cell lung cancer development. |
| ジャーナル | Oncogene |
| Abstract |
Lung cancer is one of the major causes of cancer death and clarification of its molecular pathology is highly prioritized. The physiological importance of mRNA degradation through the CCR4-NOT deadenylase has recently been highlighted. For example, mutation in CNOT3, a gene coding for CNOT3 subunit of the CCR4-NOT complex, is found to be associated with T-cell acute lymphoblastic leukemia, T-ALL, though its contribution to other cancers has not been reported. Here, we provide evidence suggesting that CNOT3 is required for the growth of non-small cell lung cancer. Depletion of CNOT3 suppresses proliferation of A549 human non-small cell lung cancer cells with enhanced mRNA stability and subsequent elevated expression of p21. In addition, we identified the mRNA for Krüppel-like factor 2 transcription factor, an inducer of p21, as a novel mRNA degradation target of CNOT3 in non-small cell lung cancer cells. Aberrant up-regulation of Krüppel-like factor 2 by CNOT3 depletion leads to impairment in the proliferation of A549 cells. Consistent with these findings, elevated mRNA expression of CNOT3 in non-small cell lung cancer in comparison with the paired normal lung epithelium was confirmed through scrutinization of the RNA-sequencing datasets from The Cancer Genome Atlas. Moreover, we found an inverse correlation between CNOT3 and CDKN1A (encoding p21) mRNA expression using the combined datasets of normal lung epithelium and non-small cell lung cancer. Thus, we propose that the up-regulation of CNOT3 facilitates the development of non-small cell lung cancer through down-regulation of Krüppel-like factor 2 and p21, contrary to tumor suppressive functions of CNOT3 in T-ALL. |
| 巻・号 | 38(14) |
| ページ | 2580-2594 |
| 公開日 | 2019-4-1 |
| DOI | 10.1038/s41388-018-0603-7 |
| PII | 10.1038/s41388-018-0603-7 |
| PMID | 30531840 |
| MeSH | A549 Cells Carcinoma, Non-Small-Cell Lung / genetics* Carcinoma, Non-Small-Cell Lung / pathology Cell Cycle / genetics* Cell Line, Tumor Cell Proliferation / genetics Cyclin-Dependent Kinase Inhibitor p21 / genetics Down-Regulation / genetics Gene Expression Regulation / genetics Humans Kruppel-Like Transcription Factors / genetics Lung Neoplasms / genetics* Lung Neoplasms / pathology Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / genetics Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology RNA Stability / genetics RNA, Messenger / genetics Respiratory Mucosa / pathology Transcription Factors / genetics* Up-Regulation / genetics |
| IF | 6.634 |
| 引用数 | 4 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | News |
| 各媒体での言及数の合計 | 3 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | A549(RCB0098) |