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.

Tripartite motif containing 62 is a novel prognostic marker and suppresses tumor metastasis via c-Jun/Slug signaling-mediated epithelial-mesenchymal transition in cervical cancer

“…We observed that overexpressed c-Jun in TRIM62 overexpression CC cells resulted in up-regulated CyclinD1 expression and down-regulated P27 expression. It is reported that c-Jun was able to activate the promoter of cyclinD1 [34], and CyclinD1 could act as a negative regulator of P27 [40]. So we speculated c-Jun might up-regulate CyclinD1 expression by activating its promoter, consequently down-regulating P27 expression.…”

c-myc regulates the sensitivity of breast cancer cells to palbociclib via c-myc/miR-29b-3p/CDK6 axis

“…MicroRNAs (miRNAs) play crucial roles in regulating cancer biology, including proliferation, apoptosis, and drug resistance 19 . Our previous studies have identified several miRNAs associated with the sensitivity of breast cancer to multiple drugs, including tamoxifen 20 , olaparib 21 , saracatinib 22 , and lapatinib 23 . To investigate whether miRNAs were associated with palbociclib sensitivity, we used microarray to establish differential miRNA expression profiles between palbociclib-sensitive cells and palbociclib-insensitive cells after palbociclib treatment.…”

Usefulness of serum microRNA as a predictive marker of recurrence and prognosis in biliary tract cancer after radical surgery

“…All six candidate miRNAs that we identified had ID names higher than 1,000, indicating that they were discovered relatively recently. Therefore, there are only a few reports describing the mechanisms through which these miRNAs are involved in various cancers or chronic diseases that cause cancers (see Supplementary Table S4) 62–69 . We could predict a total 884 target genes of six candidate miRNAs by TargetScan Human 7.2 software and Mirtarbase database.…”