| Experiment ID | EXP00248 |
| Reference | Title: MicroRNAs cooperatively inhibit a network of tumor suppressor genes to promotepancreatic tumor growth and progression. Author: Frampton AE, Castellano L, Colombo T, Giovannetti E, Krell J,Jacob J, Pellegrino L, Roca-Alonso L, Funel N, Gall TM, De GiorgioA, Pinho FG, Fulci V, Britton DJ, Ahmad R, Habib NA, CoombesRC, Harding V, Knösel T, Stebbing J, Jiao LR. Journal: Gastroenterology. 2014 Jan;146(1):268-77.e18. doi: 10.1053/j.gastro.2013.10.010. Epub 2013 Oct 9. Abstract: BACKGROUND & AIMS: There has not been a broad analysis of the combined effects ofaltered activities of microRNAs (miRNAs) in pancreatic ductal adenocarcinoma(PDAC) cells, and it is unclear how these might affect tumor progression orpatient outcomes.METHODS: We combined data from miRNA and messenger RNA (mRNA) expression profilesand bioinformatic analyses to identify an miRNA-mRNA regulatory network in PDACcell lines (PANC-1 and MIA PaCa-2) and in PDAC samples from patients. We usedthis information to identify miRNAs that contribute most to tumorigenesis.RESULTS: We identified 3 miRNAs (MIR21, MIR23A, and MIR27A) that acted ascooperative repressors of a network of tumor suppressor genes that includedPDCD4, BTG2, and NEDD4L. Inhibition of MIR21, MIR23A, and MIR27A had synergistic effects in reducing proliferation of PDAC cells in culture and growth ofxenograft tumors in mice. The level of inhibition was greater than that ofinhibition of MIR21 alone. In 91 PDAC samples from patients, high levels of acombination of MIR21, MIR23A, and MIR27A were associated with shorter survivaltimes after surgical resection.CONCLUSIONS: In an integrated data analysis, we identified functional miRNA-mRNA interactions that contribute to growth of PDACs. These findings indicate thatmiRNAs act together to promote tumor progression; therapeutic strategies mightrequire inhibition of several miRNAs. PMID: 24120476 |
| Expressiion Profile | Description: Combinatorial analysis of miRNA and mRNA expression in pancreatic ductal adenocarcinoma (PDAC)_miRNA Organism: Homo sapiens GEO ID: GSE41369 Platform: GPL16142 Number of samples: 18 |
| Design and Sample | Cancer Type: pancreatic cancer Cancer SubType: pancreatic ductal adenocarcinoma Cell Line: N/D Experimental Design: cancer vs normal Case Sample: pancreatic ductal adenocarcinoma Control Sample: normal pancreas Num of Case: 9 Num of Control: 9 Quantification Software: Limma Num of miRNAs: 654 |
| Identification | Num of Up: 54 Num of Down: 26 |