| Experiment ID | EXP00344 |
| Reference | Title: Triptolide induces the expression of miR-142-3p: a negative regulator of heatshock protein 70 and pancreatic cancer cell proliferation. Author: MacKenzie TN, Mujumdar N, Banerjee S, Sangwan V, Sarver A, Vickers S,Subramanian S, Saluja AK. Journal: Mol Cancer Ther. 2013 Jul;12(7):1266-75. doi: 10.1158/1535-7163.MCT-12-1231. Epub2013 May 1. Abstract: Pancreatic ductal adenocarcinoma (PDAC), one of the deadliest malignancies, isresistant to current chemotherapies. We previously showed that triptolideinhibits PDAC cell growth in vitro and blocks metastatic spread in vivo.Triptolide downregulates HSP70, a molecular chaperone upregulated in severaltumor types. This study investigates the mechanism by which triptolide inhibitsHSP70. Because microRNAs (miRNA) are becoming increasingly recognized as negativeregulators of gene expression, we tested whether triptolide regulates HSP70 viamiRNAs. Here, we show that triptolide as well as quercetin, but not gemcitabine, upregulated miR-142-3p in PDAC cells (MIA PaCa-2, Capan-1, and S2-013). Ectopicexpression of miR-142-3p inhibited cell proliferation, measured by electriccell-substrate impedance sensing, and decreased HSP70 expression, measured byreal-time PCR and immunoblotting, compared with controls. We showed thatmiR-142-3p directly binds to the 3'UTR of HSP70, and that this interaction isimportant as HSP70 overexpression rescued miR-142-3p-induced cell death. We foundthat miR-142-3p regulates HSP70 independently of heat shock factor 1.Furthermore, Minnelide, a water-soluble prodrug of triptolide, induced theexpression of miR-142-3p in vivo. This is the first description of anmiRNA-mediated mechanism of HSP70 regulation in cancer, making miR-142-3p anattractive target for PDAC therapeutic intervention. PMID: 23635652 |
| Expressiion Profile | Description: Analyses of mIRNA transcript level following exposure to triptolide Organism: Homo sapiens GEO ID: GSE46188 Platform: GPL8179 Number of samples: 42 |
| Design and Sample | Cancer Type: pancreatic cancer Cancer SubType: pancreatic adenocarcinoma Cell Line: PaCa-2,S2-013 Experimental Design: treatment Case Sample: pancreatic cancer treated with triptolide Control Sample: pancreatic cancer Num of Case: 24 Num of Control: 12 Quantification Software: limma Num of miRNAs: 846 |
| Identification | Num of Up: 132 Num of Down: 89 |