Informe Final
Fundación Ciencia para la Vida- Reporte Quinto Año ejecución
Autor
Valenzuela-Valdés, Pablo
Loyola-Pedevila, María Alejandra
Krauskopf, Erwin
Pérez-Acle, Tomás
Quatrini, Raquel
Rosemblatt-Silber, Mario
Pacheco, Rodrigo
Tischler, Nicole
Burzio-Eriz, Luis
Lladser, Alvaro
Orellana-López, Ariel
Wilhelm-Bavestrello, Vivian
Holmes-Salway, David
Bernales, Sebastián
Institución
Resumen
During 2012, our investigators, posdocs and students published a total of 30 papers in ISI journals (Appendix A1), presented a total of 60 communications to international and 57 to national meetings (Appendix A3). In addition, during 2012 we sent 3 new patent applications and received noticed of 3 granted patents from previous applications (Appendix A2). Another area in which our research team stands out is in obtaining new grants. At present our investigators have secured a total of 10 research grants including 6 Fondecyt, 2 Fondef and 2 Innova CORFO. Probably, one universal hallmark of cancer is down regulation of the ASncmtRNAs. As to the mechanism involves, we have determined that the oncogene E2 of the high risk HPV 16 and 18 is involve in down regulation of the ASncmtRNAs (Villota et al., JBC 2012). Also, transduction of keratinocytes with H-Ras, K-Ras and N-Ras induces down regulation of the AsncmtRNAs, suggesting that this hallmark of cancer depend on different oncogenes. Treatment of several tumor cell lines with oligonucleotides complementary to the ASncmtRNAs
induces cell death. The viability of normal cells is not affected. Knocking down the AsncmtRNAs induces disruption of the mitochondrial membrane potential, release of cytochrome C, activation of caspases and other classical hallmarks of apoptosis. Remarkable however, treated tumor cells
show down regulation of surviving and translocation of the anti-apoptotic factor Bcl-2 from ampitoopcthoosnisd irsia p otote tnhteia tneudc ilne utusm, loorc caelilzlsa tbioyn i nthhiabti titnugrn asn tBi-calp-2o pintototi ca f apcrtoo-rasp. oInp taodtidci tifoanc,t ocry. cTlinh eDre1f oarned,
cyclin B1 are also down regulated but not cyclin E, cyclin A and PCNA. Down regulation of surviving, cyclin D1 and cyclin B1 seems to be mediated by microRNAs. Bioinformatic studies reveal that these putative microRNAs derive from the double-stranded region of the AsncmtRNAs. Six of these putative miRs contain the “seed” region at the 5`end that can interact with the 3’ UTR ao f tthheer ampReuNtiAcs s otrfa ttheogsye f oprr ohtueminas n( Vciadnacuerrre. este anlt. ,f oTra prguebtliincga titohne) .m Mitoocreh ornedcerinatl lya,n wtisee hnaseve n fcoRuNndA sth aast the induction of DNA damage with doxorubicin in tumor cells (melanoma, ovary and colon) induces over-expression of the ASncmtRNAs and almost complete nuclear localization. The expression level and localization of the SncmtRNAs. These results suggest that the ASncmtRNA might be involved in DNA damage response. Centros de Investigación y Desarrollo (I+D) I Concurso Nacional de Planes de Desarrollo para Centros Científicos y Tecnológicos de Excelencia Programa de Investigación Asociativa (PIA) Programa de Investigación Asociativa (PIA) Finalizado