Journal
EXPERIMENTAL AND MOLECULAR PATHOLOGY
Volume 107, Issue -, Pages 85-94Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.yexmp.2018.11.014
Keywords
Gastric cancer; miR-141-3p; STAT4; Cancer-associated fibroblasts
Categories
Funding
- Young and Middle-aged Key Personnel Training Program for Provincial Health Planning Students [2017-ZQN-18]
- Provincial Youth Health Science Research Project [2014-2-8, 2017-1-13]
- Natural Science Foundation of Fujian [2016J01436]
- National Key Clinical Specialty Construction Project [2013-2016]
Ask authors/readers for more resources
Background: Cancer associated fibroblasts (CAFs) are known to be crucial constituents of cancer micro environment (CME) and play an important role in initiation, progression and metastasis of various types of cancer, such as oral cancer, pancreatic cancer, and gastric cancer. CAFs are usually derived from normal fibroblasts (NFs), but the mechanism of the transition in gastric cancer has not yet been fully elucidated. Methods: qRT-PCR and western blot were employed to investigate differences of miR-141 and STAT4 expression respectively. The CAF-like features and wnt/beta-catenin pathway related proteins in NF or BMSC were assessed by qRT-PCR or western blot after treated with the conditioned medium from different indicated groups of gastric cancer cells. The invasion and migration ability of AGS cells after transfection were analyzed by Transwell assay and wound healing assay. Dual-luciferase report assay was employed to determine the direct binding of miR-141 to STAT4 3' UTR. Results: For the first time, the present study found that STAT4 over-expression in gastric cancer cells induced NFs to obtain CAF-like features via activating wnt/beta-catenin pathway. Further gain-of-function and loss-of-function analysis revealed that miR-141 not only limited the migration and invasion of the gastric cancer cells, but also inhibited the transition of NFs and BMSC to CAFs. The luciferase assay indicated that miR-141 directly targeted the 3'-UTR predictive sequence of STAT4. Conclusion: Our data showed that miR-141 inhibited migration and invasion of gastric cancer cells and inhibited transition from NFs to CAFs via targeting STAT4/wnt/beta-catenin pathway.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available