MiR‐1470 mediates lapatinib induced p27 upregulation by targeting c‐jun. Issue 7 (July 2015)

• Record Type: Journal Article
• Authors: Nie, Weiwei; Song, Wei; Zhang, Wenwen; Wang, Yanru; Zhu, Aiyu; Shao, Jiaqing; Guan, Xiaoxiang
• Is Part Of: Journal of cellular physiology. Volume 230:Issue 7(2015:Jul.)
• Page Start: 1630
• Page End: 1639
• Publication Date: 2015-07
• Subjects: Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.24910
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract : Our previous study indicated that lapatinib induces p27‐dependent G1 arrest through both transcriptional and post‐translational mechanisms. Using miRNA microarray technology and quantitative RT‐PCR, we further investigated the potential miRNAs that involved in p27 upregulation and Her‐2 signaling pathway alteration with lapatinib treatment. A subset of 7 miRNAs was significantly affected in both 0.5 µM and 2.0 µM and 24 h and 48 h lapatinib treatment. Among them, only miR‐1470, miR‐126, and miR‐1208 were identified in the Her‐2 pathway after KEGG pathway analysis. However, luciferase reporter assay confirmed that miR‐1470 directly recognized the 3′‐untranslated region of c‐jun transcripts, which was consistent with TargetScan analysis. miR‐1470 significantly decreased c‐jun expression, thus miR‐1470 may repressc‐jun activation of cyclinD1 expression, and consequently promoted the upregulation of p27, a key molecule in the cell cycle arrest. Taken together, the present study provided the first evidences that miR‐1470 mediated lapatinib induced p27 upregulation by targeting c‐jun. J. Cell. Physiol. 230: 1630–1639, 2015. © 2014 Wiley Periodicals, Inc., A Wiley Company