@Article{096504017X14934840662335,
AUTHOR = {Lulin Zhang, Jun Yao, Wenyao Li, Ce Zhang},
TITLE = {Micro-RNA-21 Regulates Cancer-Associated Fibroblast-Mediated  Drug Resistance in Pancreatic Cancer},
JOURNAL = {Oncology Research},
VOLUME = {26},
YEAR = {2018},
NUMBER = {6},
PAGES = {827--836},
URL = {http://www.techscience.com/or/v26n6/56696},
ISSN = {1555-3906},
ABSTRACT = {Pancreatic ductal adenocarcinoma (PDAC) is one of the leading causes of cancer deaths due to its highly 
aggressive biological nature and resistance to chemotherapy. Previous studies indicate that miR-21 is an important regulator in the activation of cancer-associated fibroblasts (CAFs). However, whether miR-21 in CAFs 
would regulate PDAC’s tumor microenvironment and lead to drug resistance remain unknown. In this study, 
we evaluated the relationship between CAF activation, miR-21 expression, and drug resistance using tumor 
samples from PDAC patients. We changed the miR-21 expression level in CAFs and tested its roles in regulating the function of CAFs. In addition, we explored the roles of miR-21 in CAFs in the development of PDAC 
using an animal model. We found that PDAC patients who were resistant to gemcitabine treatment tended 
to have higher miR-21 expression and more activated CAFs. An in vitro study showed that CAFs with high 
miR-21 expression had elevated MMP-3, MMP-9, PDGF, and CCL-7 expression and promoted the invasion of 
PDAC cell lines. miR-21 overexpression also contributed to the activation of CAFs by regulating the PDCD4 
gene. The in vivo study showed that upregulating miR-21 in CAFs promoted PDAC desmoplasia and increased 
its drug resistance to gemcitabine treatment, but downregulating miR-21 in CAFs suppressed desmoplasia and 
enhanced the effect of gemcitabine. We concluded that miR-21 promoted the activation of CAFs and contributed to the drug resistance of PDAC.},
DOI = {10.3727/096504017X14934840662335}
}