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Dernière mise à jour : Mai 2018

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SAPS Guest Seminar, Thursday November 5 at 15h

Thursday 5 November at 15h - Webinaire

Veronica Burzio, guest speaker
Veronica Burzio will talk on: "Targeting long non-coding mitochondrial RNA for cancer therapy."

Non-Coding RNA in Nuclear-Mitochondrial Crosstalk : Applications for RNA Medicine - New Topic 2020

Title: Targeting long non-coding mitochondrial RNA for cancer therapy
Abstract
The long noncoding mitochondrial RNA (ncmtRNAs) constitute a family of transcripts comprising sense (SncmtRNA) and antisense (ASncmtRNA) members. These transcripts are differentially expressed in human and mouse tumor and normal cells: SncmtRNA is readily detected by in situ hybridization in normal and tumor cells, while ASncmtRNA is detectable in normal cells but displays a strong downregulation in tumor cells. This downregulation is a vulnerability of tumor cells since knockdown of these transcripts with antisense oligonucleotides (ASO) triggers proliferation blockage, apoptotic death and metastatic reduction in tumor cells, whilst leaving healthy cells unharmed. This approach has been used successfully in preclinical models of melanoma and breast, bladder and kidney cancer, and is presently under study in Clinical Trials. The molecular aspects underlying the selective effects of the treatment on malignant cells encompass strong downregulation of key cell cycle progression factors, including cyclins B1 and D1, CDK1 and 4 and survivin, which is also a survival factor. Taken together, our results support the application of this approach for the development of a therapeutic option against different types of cancer.
References:
Christopher Fitzpatrick, Maximiliano F. Bendek, Macarena Briones, Nicole Farfán, Valeria A. Silva, Gino Nardocci, Martín Montecino, Anne Boland, Jean-François Deleuze, Jaime Villegas, Claudio Villota, Verónica Silva, Lorena Lobos-Gonzalez, Vincenzo Borgna, Eric Barrey, Luis O. Burzio and Verónica A. Burzio*. Mitochondrial ncRNA targeting induces cell cycle arrest and tumor growth inhibition of MDA-MB-231 breast cancer cells through reduction of key cell cycle progression factors. Cell Death Dis. 10:423. doi: 10.1038/s41419-019-1649-3.
Varas-Godoy M, Lladser A, Farfan N, Villota C, Villegas J, Tapia JC, Burzio LO, Burzio VA*, Valenzuela PDT. (2018) In vivo knockdown of antisense non-coding mitochondrial RNAs by a lentiviral-encoded shRNA inhibits melanoma tumor growth and lung colonization. Pigment Cell Melanoma Res. 31: 64-72.
Borgna V, Villegas J, Burzio VA*, Belmar S, Araya M, Jeldes E, Lobos-González L, Silva V, Villota C, Oliveira-Cruz L, Lopez C, Socias T, Castillo O, Burzio LO. (2016) Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model. Oncotarget. 8: 43692-43708.
Lorena Lobos-González, Verónica Silva, Mariela Araya, Franko Restovic, Javiera Echenique, Luciana Oliveira-Cruz, Christopher Fitzpatrick, Macarena Briones, Jaime Villegas, Claudio Villota, Soledad Vidaurre, Vincenzo Borgna, Miguel Socias, Sebastián Valenzuela, Constanza Lopez, Teresa Socias, Manuel Varas, Jorge Díaz, Luis O. Burzio, Verónica A. Burzio*. (2016) Targeting antisense mitochondrial ncRNAs inhibits murine melanoma tumor growth and metastasis through reduction in survival and invasion factors. Oncotarget, 7: 58331-58350.
Vidaurre S, Fitzpatrick C, Burzio VA, Briones M, Villota C, Villegas J, Echenique J, Oliveira-Cruz L, Araya M, Borgna V, Socías T, Lopez C, Avila R, Burzio LO. (2014) Down-regulation of the Antisense Mitochondrial ncRNAs is a Unique Vulnerability of Cancer Cells and a Potential Target for Cancer Therapy. J Biol Chem. 289:27182-98.
Invitée par Eric Barrey, UMR GABI, équipe BIGE

Auteur: Veronica Burzio (vburzio@unab.cl)
Affiliations: Universidad Andrés Bello, Fundación Ciencia & Vida, Andes Biotechnologies SpA, Santiago, Chile