| RRC ID |
64537
|
| Author |
Tu MJ, Pan YZ, Qiu JX, Kim EJ, Yu AM.
|
| Title |
MicroRNA-1291 targets the FOXA2-AGR2 pathway to suppress pancreatic cancer cell proliferation and tumorigenesis.
|
| Journal |
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.
|
| Volume |
7(29)
|
| Pages |
45547-45561
|
| Published |
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
|
| Resource |
| Human and Animal Cells |
HuH-7 |
