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. Cell Death and Disease (2012) 3, e423; doi:10.1038/cddis.2012.160; published online 15 November 2012
miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer / A., Sacconi; F., Biagioni; V., Canu; F., Mori; A., Di Benedetto; Lorenzon, Laura; C., Ercolani; S., Di Agostino; A. m., Cambria; S., Germoni; G., Grasso; R., Blandino; V., Panebianco; Ziparo, Vincenzo; O., Federici; P., Muti; S., Strano; F., Carboni; M., Mottolese; M., Diodoro; E., Pescarmona; A., Garofalo; G., Blandino. - In: CELL DEATH & DISEASE. - ISSN 2041-4889. - 3:11(2012), p. e423. [10.1038/cddis.2012.160]
miR-204 targets Bcl-2 expression and enhances responsiveness of gastric cancer
LORENZON, LAURA;ZIPARO, Vincenzo;
2012
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. Cell Death and Disease (2012) 3, e423; doi:10.1038/cddis.2012.160; published online 15 November 2012I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
