miR-1470 mediates lapatinib induced p27 upregulation by targeting c-jun
Weiwei Nie1, Wei Song, Wenwen Zhang
1Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, P.R. China.
Journal of Cellular Physiology
|December 30, 2014
Summary
Lapatinib treatment upregulates p27, a cell cycle arrest molecule, through microRNA-1470 targeting c-jun. This study reveals a novel mechanism for lapatinib
Area of Science:
- Molecular Biology
- Cancer Research
- Cell Cycle Regulation
Background:
- Lapatinib induces G1 arrest via transcriptional and post-translational mechanisms.
- MicroRNAs (miRNAs) play roles in cancer signaling pathways.
Purpose of the Study:
- Investigate miRNAs involved in lapatinib-induced p27 upregulation.
- Elucidate the role of miRNAs in the Her-2 signaling pathway alterations.
Main Methods:
- miRNA microarray analysis
- Quantitative RT-PCR
- KEGG pathway analysis
- Luciferase reporter assay
Main Results:
- Seven miRNAs were significantly affected by lapatinib treatment.
- miR-1470, miR-126, and miR-1208 were identified in the Her-2 pathway.
- miR-1470 directly targets c-jun, decreasing its expression.
- miR-1470 represses c-jun activation of cyclin D1, promoting p27 upregulation.
Conclusions:
- miR-1470 mediates lapatinib-induced p27 upregulation by targeting c-jun.
- This identifies a novel molecular mechanism for lapatinib's anti-cancer effects.
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