title: miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer.
abstract: Micro RNAs (miRs) are small non-coding RNAs aberrantly expressed in human tumors. Here, we aim to identify miRs whose deregulated expression leads to the activation of oncogenic pathways in human gastric cancers (GCs). Thirty nine out of 123 tumoral and matched uninvolved peritumoral gastric specimens from three independent European subsets of patients were analyzed for the expression of 851 human miRs using Agilent Platform. The remaining 84 samples were used to validate miRs differentially expressed between tumoral and matched peritumoral specimens by qPCR. miR-204 falls into a group of eight miRs differentially expressed between tumoral and peritumoral samples. Downregulation of miR-204 has prognostic value and correlates with increased staining of Bcl-2 protein in tumoral specimens. Ectopic expression of miR-204 inhibited colony forming ability, migration and tumor engraftment of GC cells. miR-204 targeted Bcl-2 messenger RNA and increased responsiveness of GC cells to 5-fluorouracil and oxaliplatin treatment. Ectopic expression of Bcl-2 protein counteracted miR-204 pro-apoptotic activity in response to 5-fluorouracil. Altogether, these findings suggest that modulation of aberrant expression of miR-204, which in turn releases oncogenic Bcl-2 protein activity might hold promise for preventive and therapeutic strategies of GC.
authors.affiliation: Translational Oncogenomic Unit, Italian National Cancer Institute Regina Elena, Rome, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Sacconi
authors.forename: F
authors.initials: F
authors.lastname: Biagioni
authors.forename: V
authors.initials: V
authors.lastname: Canu
authors.forename: F
authors.initials: F
authors.lastname: Mori
authors.forename: A
authors.initials: A
authors.lastname: Di Benedetto
authors.forename: L
authors.initials: L
authors.lastname: Lorenzon
authors.forename: C
authors.initials: C
authors.lastname: Ercolani
authors.forename: S
authors.initials: S
authors.lastname: Di Agostino
authors.forename: A M
authors.initials: AM
authors.lastname: Cambria
authors.forename: S
authors.initials: S
authors.lastname: Germoni
authors.forename: G
authors.initials: G
authors.lastname: Grasso
authors.forename: R
authors.initials: R
authors.lastname: Blandino
authors.forename: V
authors.initials: V
authors.lastname: Panebianco
authors.forename: V
authors.initials: V
authors.lastname: Ziparo
authors.forename: O
authors.initials: O
authors.lastname: Federici
authors.forename: P
authors.initials: P
authors.lastname: Muti
authors.forename: S
authors.initials: S
authors.lastname: Strano
authors.forename: F
authors.initials: F
authors.lastname: Carboni
authors.forename: M
authors.initials: M
authors.lastname: Mottolese
authors.forename: M
authors.initials: M
authors.lastname: Diodoro
authors.forename: E
authors.initials: E
authors.lastname: Pescarmona
authors.forename: A
authors.initials: A
authors.lastname: Garofalo
authors.forename: G
authors.initials: G
authors.lastname: Blandino
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D045744:Cell Line, Tumor; D005472:Fluorouracil / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D000970:Antineoplastic Agents; C549404:MIRN204 microRNA, human; D035683:MicroRNAs; D009944:Organoplatinum Compounds; D019253:Proto-Oncogene Proteins c-bcl-2; D000077150:Oxaliplatin; D005472:Fluorouracil