miR-33a suppresses the nuclear translocation of β-catenin to enhance gemcitabine sensitivity in human pancreatic cancer cells.
Tumour Biol. 2015 Jun 26;
Authors: Liang C, Wang Z, Li YY, Yu BH, Zhang F, Li HY
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, partly due to its high level of drug resistance. β-Catenin is critical for drug resistance in pancreatic cancer, which occurs through multiple mechanisms. Here, we observed that miR-33a targeted the 3'UTR of β-catenin, inducing apoptosis and inhibiting the growth of human pancreatic cancer cells. Moreover, gemcitabine (GEM) treatment enhanced β-catenin expression by reducing miR-33a expression in a dose-dependent manner. GEM-resistant MiaPaCa-2(res) cells with a low level of miR-33a expression and high level of β-catenin expression adopted spindle-shaped morphologies, similar to their morphologies during the epithelial-to-mesenchymal transition (EMT), and their normal morphologies were restored by miR-33a overexpression. Furthermore, miR-33a downregulated β-catenin nuclear translocation, decreasing the transcription of survivin, cyclin D1, and MDR-1, and the protein expression of slug, vimentin, and N-cadherin, thereby mediating sensitization to GEM. Thus, miR-33a might function as a tumor suppressor to downregulate β-catenin expression, affecting cell growth, apoptosis, the EMT, and GEM resistance.
PMID: 26113407 [PubMed - as supplied by publisher]