title: The rescue of miR-148a expression in pancreatic cancer: an inappropriate therapeutic tool.
abstract: MicroRNAs are small non-coding RNAs that physiologically modulate proteins expression, and regulate numerous cellular mechanisms. Alteration of microRNA expression has been described in cancer and is associated to tumor initiation and progression. The microRNA 148a (miR-148a) is frequently down-regulated in cancer. We previously demonstrated that its down-regulation by DNA hypermethylation is an early event in pancreatic ductal adenocarcinoma (PDAC) carcinogenesis, suggesting a tumor suppressive function. Here, we investigate the potential role of miR-148a over-expression in PDAC as a therapeutic tool. We first report the consequences of miR-148a over-expression in PDAC cell lines. We demonstrate that miR-148a over-expression has no dramatic effect on cell proliferation and cell chemo-sensitivity in four well described PDAC cell lines. We also investigate the modulation of protein expression by a global proteomic approach (2D-DIGE). We show that despite its massive over-expression, miR-148a weakly modulates protein expression, thus preventing the identification of protein targets in PDAC cell lines. More importantly, in vivo data demonstrate that modulating miR-148a expression either in the epithelia tumor cells and/or in the tumor microenvironment does not impede tumor growth. Taken together, we demonstrate herein that miR-148a does not impact PDAC proliferation both in vitro and in vivo thus suggesting a weak potential as a therapeutic tool.
authors: INSERM UMR 1037-University of Toulouse III, Cancer Research Center of Toulouse (CRCT), Toulouse, France.
authors: Yannick
authors: Y
authors: Delpu
authors: Hubert
authors: H
authors: Lulka
authors: Flavie
authors: F
authors: Sicard
authors: Nathalie
authors: N
authors: Saint-Laurent
authors: Frédéric
authors: F
authors: Lopez
authors: Naïma
authors: N
authors: Hanoun
authors: Louis
authors: L
authors: Buscail
authors: Pierre
authors: P
authors: Cordelier
authors: Jérôme
authors: J
authors: Torrisani
mesh_terms: D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003841:Deoxycytidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004195:Disease Models, Animal; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D015870:Gene Expression; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy; D020543:Proteome; D040901:Proteomics; D023041:Xenograft Model Antitumor Assays; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; C550570:MIRN148 microRNA, human; D035683:MicroRNAs; D020543:Proteome; D003841:Deoxycytidine; D000093542:Gemcitabine
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