Non-coding RNAs & Cancer

PROFILE

Cancer is a group of diseases that share a commonality of uncontrolled growth of affected cells leading to tumors, metastases and, in many cases, death. There is presently no definitive cure for cancer and the available treatments are very aggressive, with devastating effects on normal as well as tumor tissue.

Our group has discovered a novel family of ribonucleic acid (RNA) molecular biomarkers of mitochondrial origin, which have proven to be universal targets for diagnostics and therapy of cancer. For the therapeutic approach we are developing drugs which target cancer cells selectively, leaving normal cells unaffected. Also, this differential pattern allows for development of a universal diagnostic tool, independent of the tissue of origin. At present, we are focused on a subset of human and mouse tumor models including melanoma (skin cancer), uterine cervix cancer and bladder cancer. The administration of the oligonucleotide therapy in cancer models has proven to significantly slow the growth and eventually eliminate tumors in mice. We are completing preclinical studies to extend these findings to the eventual treatment of human tumors.

LAB MEMBERS

Research Head: Luis O. Burzio

Senior Investigators: Jaime Villegas • Verónica Burzio • Claudio Villota

Principal Investigators: Lorena Lobos-Gonzalez

Postdoctoral Fellows: Soledad Vidaurre • Luciana Oliveira-Cruz • Vincenzo Borgna

Doctoral students: Christopher Fitzpatrick Maximiliano Bendek • Nicole Farfán • Emanuel Jeldes

Undergraduate students: Rocío Bustos

Research Assistants: Mariela Araya • Macarena Briones • Constanza Lopez • Teresa Socias • Verónica Silva

SELECTED PUBLICATIONS

  • Vincenzo Borgna, Lorena Lobos-González, Francisca Guevara, Eduardo Landerer, Maximiliano Bendek, Rodolfo Ávila, Verónica Silva, Claudio Villota, Mariela Araya, Alexis Rivas, Constanza López, Teresa Socias, Jorge Castillo, Luis Alarcón, Luis O. Burzio, Verónica A. Burzio and Jaime Villegas. (2020) Targeting antisense mitochondrial noncoding RNAs induces bladder cancer cell death and inhibition of tumor growth through reduction of survival and invasion factors. Journal of Cancer 11(7): 1780-1791. doi:10.7150/jca.38880 | PDF | ABSTRACT
  • 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 | PDF | ABSTRACT
  • Claudio Villota, Manuel Varas-Godoy, Emanuel Jeldes, América Campos, Jaime Villegas, Vincenzo Borgna, Luis O.Burzio and Verónica A. Burzio* (2018) HPV-18 E2 protein downregulates antisense noncoding mitochondrial RNA-2, delaying replicative senescence of human keratinocytes. Aging (Albany NY) 11:33-47 | PDF | ABSTRACT
  • 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 | PDF | ABSTRACT
  • 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 | PDF | ABSTRACT
  • 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. | PDF | ABSTRACT
  • 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 | PDF | ABSTRACT
  • Lobos-Gonzalez L, Aguilar-Guzmán L, Fernandez JG, Muñoz N, Hossain M, Bieneck S, Silva V, Burzio V, Sviderskaya EV, Bennett DC, Leyton L, Quest AF. (2014) Caveolin-1 is a risk factor for postsurgery metastasis in preclinical melanoma models. Melanoma Res. 24: 108-19 | PDF | ABSTRACT
  • Rivas A, Burzio V, Landerer E, Borgna V, Gatica S, Ávila R, López C, Villota C, de la Fuente R, Echenique J, Burzio LO, Villegas J. (2012) Determination of the differential expression of mitochondrial long non-coding RNAs as a noninvasive diagnosis of bladder cancer. BMC Urol. 12: 37 | PDF | ABSTRACT
  • Villota C., Cifuentes-Muñoz N., Burzio L.O. Human Papillomavirus and non-coding RNAs: from basics to diagnostic. (2014) | PDF | ABSTRACT
  • Villota C, América Campos A, Soledad Vidaurre S, Oliveira-Cruz L, Boccardo E, Burzio V, Varas M, Villegas J, Villa L, Valenzuela PD, Socias M, Roberts S, Burzio L.O. Expression of Mitochondrial Non-coding RNAs (ncRNAs) Is Modulated by High Risk Human Papillomavirus (HPV) Oncogenes. The Journal of Biological Chemistry, vol. 287. 25, pp. 21303–21315. (2012) | PDF | ABSTRACT
  • Villegas J, Dadlan K, Ávila R, Villota C, Burzio V, López C, Socias M, Zapata L,Burzio L.O. The Mitochondrial Antisense ncRNAs are Down-Regulated in Early Cervical Carcinoma. Cancer Science & Therapy, S7 (2013). | PDF | ABSTRACT
  • Rivas A, Burzio V, Landerer E, Borgna V, Gatica S, Ávila R, López C, Villota C, De la Fuente R, Echenique J, Burzio L.O.Determination of the differential expression of mitochondrial long non-coding RNAs as a noninvasive diagnosis of bladder cancer. BMC Urology, 12:37 (2012) | PDF | ABSTRACT
  • Landerer E., Villegas J., Burzio A. V., Oliveira L., Villota C., López C., Restovic F., Martínez R., Castillo O. and Burzio L. O. Nuclear localization of the mitochindrial ncRNAs in normal and cancer cells. Cell. Oncol. 34, 297-305 (2011) | PDF | ABSTRACT
  • Burzio V.A., Villota C., Villegas J., Landerer E., Boccardo E., Villa L.L, Martínez R., López C., Gaete F., Toro V., Rodriguez X. and Burzio L.O. Expression of a family of noncoding mitochondrial RNAs distinguishes normal from cancer cells. PNAS 106 (23): 9430-9434 (2009) | PDF | ABSTRACT
  • Albornoz A., Yáñez J. M., Foerster C., Aguirre C., Pereiro L., Burzio V., Moraga M., Reyes A. E. and Antonelli M. The CK1 gene family: expression patterning in zebrafish development. Biol. Res. 40, 251-266 (2007) | PDF | ABSTRACT
  • Villegas J., Burzio V., Villota C., Landerer E., Martínez R., Santander M., Martinez R., Pinto R., Vera M. I., Boccardo E., Villa L. L. and Burzio L. O. Expression of a novel non-coding mitochondrial RNA in human proliferating cells. NAR 35 (21): 7336-7347 (2007) | PDF | ABSTRACT
  • Marin O., Burzio V., Boschetti M., Meggio F., Allende C. C., Allende J. E. and Pinna L. A. Structural Features Underlying the Multisite Phosphorylation of the A Domain of the NF-AT4 Transcription Factor by Protein Kinase CK1. Biochemistry 41, 618-627 (2002) | PDF | ABSTRACT
  • Bronfman M., Nuñez L., Orellana A., Burzio V. and Hidalgo P. Peroxisome Proliferators and Signal Transduction. ANN N. Y. Acad. Sci. 27 (804): 403-412 (1996) | PDF | ABSTRACT