Details

Autor(en) / Beteiligte

• Dong, Jie
• Zhao, Yu-Pei
• Zhou, Li
• Zhang, Tai-Ping
• Chen, Ge

Titel

Bcl-2 Upregulation Induced by miR-21 Via a Direct Interaction Is Associated with Apoptosis and Chemoresistance in MIA PaCa-2 Pancreatic Cancer Cells

Ist Teil von

• Archives of medical research, 2011, Vol.42 (1), p.8-14

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2011

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• Background and Aims Bcl-2 was previously shown to be associated with apoptosis and chemoresistance and carry multiple regulating pathways. However, the roles and mechanisms of miRNA (miR)-21 in regulation of Bcl-2 in pancreatic cancer remain to be elucidated. The aim of this study was to explore the regulation of Bcl-2 expression by miR-21 and its impact on apoptosis, chemoresistance and growth of pancreatic cancer cells using a pancreatic cancer cell line, MIA PaCa-2. Methods miR-21 mimics and inhibitor were transfected to MIA PaCa-2 pancreatic cancer cells, respectively. Alteration in Bcl-2/Bax expression was subsequently evaluated. Then, luciferase activity was observed after miR-21 mimics and pRL-TK plasmids containing wild-type and mutant 3′UTRs of Bcl-2 mRNA were co-transfected. Finally, apoptosis, chemosensitivity to gemcitabine and cell proliferation were evaluated. Results Upregulation of Bcl-2 expression was detected in cells transfected with miR-21 mimics, accompanied by downregulated Bax expression, less apoptosis, lower caspase-3 activity, decreased chemosensitivity to gemcitabine and increased proliferation compared with the control cells. Cells transfected with miR-21 inhibitor revealed an opposite trend. There was a significant increase in luciferase activity in the cells transfected with the wild-type pRL-TK plasmid, in contrast to those transfected with the mutant one, indicating that miR-21 promotes Bcl-2 expression by binding directly to the 3′UTR of Bcl-2 mRNA. Conclusions Upregulation of Bcl-2 directly induced by miR-21 is associated with apoptosis, chemoresistance and proliferation of MIA PaCa-2 pancreatic cancer cells.