Unknown

Dataset Information

0

MiR-1266 Contributes to Pancreatic Cancer Progression and Chemoresistance by the STAT3 and NF-?B Signaling Pathways.


ABSTRACT: Pancreatic cancer is characterized by chemoresistance after several cycles of chemotherapy, which is a major issue responsible for treatment failure of pancreatic cancer. Therefore, it is necessary to explore the specific mechanism underlying chemotherapeutic resistance to overcome this issue. Here we report that miR-1266 is dramatically elevated and correlates with poor survival and chemotherapy response in pancreatic cancer patients. Upregulation of miR-1266 enhanced the chemoresistance of pancreatic cancer cells to gemcitabine (GEM) in vitro and in vivo; conversely, inhibition of miR-1266 yielded the opposite effect. Importantly, silencing of miR-1266 restored the sensitivity of pancreatic cancer cells to GEM in a dose-dependent manner in vivo. Furthermore, our results demonstrate that miR-1266 promotes resistance of pancreatic cancer cells to GEM by targeting multiple negative regulators of the STAT3 and NF-?B pathways, including SOCS3, PTPN11, ITCH, and TNIP1, leading to constitutive activation of STAT3 and NF-?B signaling. Thus, our findings clarify a novel mechanism by which miR-1266 induces chemotherapeutic resistance in pancreatic cancer, indicating that miR-1266 may be used as chemotherapeutic response indicator. Antagomir-1266 as a chemotherapeutic sensitizer, in combination with GEM, may serve as a rational regimen in the treatment of chemotherapy-resistant pancreatic cancer.

SUBMITTER: Zhang X 

PROVIDER: S-EPMC5842289 | BioStudies | 2018-01-01

REPOSITORIES: biostudies

Similar Datasets

1000-01-01 | S-EPMC4381607 | BioStudies
2020-01-01 | S-EPMC7086345 | BioStudies
1000-01-01 | S-EPMC5746084 | BioStudies
2017-01-01 | S-EPMC6710626 | BioStudies
| S-EPMC7023912 | BioStudies
2020-01-01 | S-EPMC7673723 | BioStudies
2017-01-01 | S-EPMC5750480 | BioStudies
2019-01-01 | S-EPMC6920852 | BioStudies
1000-01-01 | S-EPMC5226588 | BioStudies
2009-01-01 | S-EPMC2806309 | BioStudies