title: miR-1470 mediates lapatinib induced p27 upregulation by targeting c-jun.
abstract: Our previous study indicated that lapatinib induces p27-dependent G(1) 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.
authors.affiliation: Department of Medical Oncology, Jinling Hospital, School of Medicine, Southern Medical University, Guangzhou, P.R. China.
authors.forename: Weiwei
authors.initials: W
authors.lastname: Nie
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Wenwen
authors.initials: W
authors.lastname: Zhang
authors.forename: Yanru
authors.initials: Y
authors.lastname: Wang
authors.forename: Aiyu
authors.initials: A
authors.lastname: Zhu
authors.forename: Jiaqing
authors.initials: J
authors.lastname: Shao
authors.forename: Xiaoxiang
authors.initials: X
authors.lastname: Guan
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D001943:Breast Neoplasms / Q000378:metabolism; D045744:Cell Line, Tumor; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D000077341:Lapatinib; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D018809:Proliferating Cell Nuclear Antigen / Q000235:genetics / Q000378:metabolism*; D011799:Quinazolines / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; D048031:JNK Mitogen-Activated Protein Kinases; D000077341:Lapatinib; D035683:MicroRNAs; D018809:Proliferating Cell Nuclear Antigen; D011799:Quinazolines; D018719:Erb-b2 Receptor Tyrosine Kinases; C413374:p27 antigen; C508053:ERBB2 protein, human