期刊
JOURNAL OF CELLULAR BIOCHEMISTRY
卷 119, 期 1, 页码 1027-1040出版社
WILEY
DOI: 10.1002/jcb.26270
关键词
CUL4B; epithelial-mesenchymal transition; invasion; microRNA-300; migration; pancreatic cancer; Wnt; -catenin signaling pathway
资金
- National Science Foundation of China [81472237]
The study aims to verify the hypothesis that up-regulation of microRNA-300 (miR-300) targeting CUL4B promotes apoptosis and suppresses proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells by regulating the Wnt/-catenin signaling pathway. Pancreatic cancer tissues and adjacent tissues were collected from 110 pancreatic cancer patients. Expression of miR-300, CUL4B, Wnt, -catenin, E-cadherin, N-cadherin, Snail, GSK-3, and CyclinD1 were detected using qRT-PCR and Western blot. CFPAC-1, Capan-1, and PANC-1 were classified into blank, negative control (NC), miR-300 mimics, miR-300 inhibitors, siRNA-CUL4B, and miR-300 inhibitors+siRNA-CUL4B groups. The proliferation, migration, invasion abilities, the cell cycle distribution, and apoptosis rates were measured in CCK-8 and Transwell assays. Pancreatic cancer tissues showed increased CUL4B expression but decreased miR-300 expression. When miR-300 was lowly expressed, CUL4B was upregulated which in-turn activated the Wnt/-catenin pathway to protect the -catenin expression and thus induce EMT. When miR-300 was highly expressed, CUL4B was downregulated which in-turn inhibited the Wnt/-catenin pathway to prevent EMT. Weakened cell migration and invasion abilities and enhanced apoptosis were observed in the CUL4B group. The miR-300 inhibitors group exhibited an evident increase in growth rate accompanied the largest tumor volume. Smaller tumor volume and slower growth rate were observed in the miR-300 mimics and siRNA-CUL4B group. Our study concludes that lowly expressed miR-300 may contribute to highly expressed CUL4B activating the Wnt/-catenin signaling pathway and further stimulating EMT, thus promoting proliferation and migration but suppressing apoptosis of pancreatic cancer cells.
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