論文 - 詳細
| RRC ID | 64537 |
|---|---|
| 著者 | Tu MJ, Pan YZ, Qiu JX, Kim EJ, Yu AM. |
| タイトル | MicroRNA-1291 targets the FOXA2-AGR2 pathway to suppress pancreatic cancer cell proliferation and tumorigenesis. |
| ジャーナル | Oncotarget |
| Abstract |
Pancreatic cancer is the fourth leading cause of cancer death in the United States. Better understanding of pancreatic cancer biology may help identify new oncotargets towards more effective therapies. This study investigated the mechanistic actions of microRNA-1291 (miR-1291) in the suppression of pancreatic tumorigenesis. Our data showed that miR-1291 was downregulated in a set of clinical pancreatic carcinoma specimens and human pancreatic cancer cell lines. Restoration of miR-1291 expression inhibited pancreatic cancer cell proliferation, which was associated with cell cycle arrest and enhanced apoptosis. Furthermore, miR-1291 sharply suppressed the tumorigenicity of PANC-1 cells in mouse models. A proteomic profiling study revealed 32 proteins altered over 2-fold in miR-1291-expressing PANC-1 cells that could be assembled into multiple critical pathways for cancer. Among them anterior gradient 2 (AGR2) was reduced to the greatest degree. Through computational and experimental studies we further identified that forkhead box protein A2 (FOXA2), a transcription factor governing AGR2 expression, was a direct target of miR-1291. These results connect miR-1291 to the FOXA2-AGR2 regulatory pathway in the suppression of pancreatic cancer cell proliferation and tumorigenesis, providing new insight into the development of miRNA-based therapy to combat pancreatic cancer. |
| 巻・号 | 7(29) |
| ページ | 45547-45561 |
| 公開日 | 2016-7-19 |
| DOI | 10.18632/oncotarget.9999 |
| PII | 9999 |
| PMID | 27322206 |
| PMC | PMC5216741 |
| MeSH | Adenocarcinoma / genetics Adenocarcinoma / metabolism Adenocarcinoma / pathology* Adult Aged Aged, 80 and over Animals Cell Line, Tumor Cell Proliferation / genetics Cell Transformation, Neoplastic / genetics* Cell Transformation, Neoplastic / metabolism Cell Transformation, Neoplastic / pathology Female Gene Expression Regulation, Neoplastic / physiology* Hepatocyte Nuclear Factor 3-beta / metabolism Heterografts Humans Male Mice Mice, Nude MicroRNAs / genetics MicroRNAs / metabolism* Middle Aged Mucoproteins Oncogene Proteins Pancreatic Neoplasms / genetics Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology* Proteins / metabolism |
| IF | 5.168 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 1 |
| 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 | HuH-7 |