Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model

Vincenzo Borgna, Jaime Villegas, Verónica A. Burzio, Sebastián Belmar, Mariela Araya, Emanuel Jeldes, Lorena Lobos-González, Verónica Silva, Claudio Villota, Luciana Oliveira-Cruz, Constanza Lopez, Teresa Socias, Octavio Castillo, Luis O. Burzio

Resultado de la investigación: Article

6 Citas (Scopus)

Resumen

Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule. These studies showed inhibition of tumor growth and metastasis. Direct metastasis assessment by tail vein injection of RenCa cells also showed a drastic reduction in lung metastatic nodules. In vivo treatment reduces survivin, N-cadherin and P-cadherin levels, providing a molecular basis for metastasis inhibition. In consequence, the treatment significantly enhanced mouse survival in these models. Our results suggest that the ASncmtRNAs could be potent and selective targets for therapy against human renal cell carcinoma.

Idioma originalEnglish
Páginas (desde-hasta)43692-43708
Número de páginas17
PublicaciónOncotarget
Volumen8
N.º27
DOI
EstadoPublished - 2017

Huella dactilar

Renal Cell Carcinoma
Antisense RNA
Untranslated RNA
Neoplasm Metastasis
Growth
Cadherins
Neoplasms
Kidney
Therapeutics
Kidney Neoplasms
Tumor Cell Line
Capsules
Tail
Veins
Epithelial Cells
Apoptosis
Lung
Injections
mitochondrial RNA

ASJC Scopus subject areas

  • Oncology

Citar esto

Borgna, Vincenzo ; Villegas, Jaime ; Burzio, Verónica A. ; Belmar, Sebastián ; Araya, Mariela ; Jeldes, Emanuel ; Lobos-González, Lorena ; Silva, Verónica ; Villota, Claudio ; Oliveira-Cruz, Luciana ; Lopez, Constanza ; Socias, Teresa ; Castillo, Octavio ; Burzio, Luis O. / Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model. En: Oncotarget. 2017 ; Vol. 8, N.º 27. pp. 43692-43708.
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title = "Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model",
abstract = "Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule. These studies showed inhibition of tumor growth and metastasis. Direct metastasis assessment by tail vein injection of RenCa cells also showed a drastic reduction in lung metastatic nodules. In vivo treatment reduces survivin, N-cadherin and P-cadherin levels, providing a molecular basis for metastasis inhibition. In consequence, the treatment significantly enhanced mouse survival in these models. Our results suggest that the ASncmtRNAs could be potent and selective targets for therapy against human renal cell carcinoma.",
keywords = "Antisense therapy, Mitochondria, Murine renal cancer, NcRNA",
author = "Vincenzo Borgna and Jaime Villegas and Burzio, {Ver{\'o}nica A.} and Sebasti{\'a}n Belmar and Mariela Araya and Emanuel Jeldes and Lorena Lobos-Gonz{\'a}lez and Ver{\'o}nica Silva and Claudio Villota and Luciana Oliveira-Cruz and Constanza Lopez and Teresa Socias and Octavio Castillo and Burzio, {Luis O.}",
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doi = "10.18632/oncotarget.18460",
language = "English",
volume = "8",
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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 2017, 'Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model', Oncotarget, vol. 8, n.º 27, pp. 43692-43708. https://doi.org/10.18632/oncotarget.18460

Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model. / Borgna, Vincenzo; Villegas, Jaime; Burzio, Verónica A.; Belmar, Sebastián; Araya, Mariela; Jeldes, Emanuel; Lobos-González, Lorena; Silva, Verónica; Villota, Claudio; Oliveira-Cruz, Luciana; Lopez, Constanza; Socias, Teresa; Castillo, Octavio; Burzio, Luis O.

En: Oncotarget, Vol. 8, N.º 27, 2017, p. 43692-43708.

Resultado de la investigación: Article

TY - JOUR

T1 - Mitochondrial ASncmtRNA-1 and ASncmtRNA-2 as potent targets to inhibit tumor growth and metastasis in the RenCa murine renal adenocarcinoma model

AU - Borgna, Vincenzo

AU - Villegas, Jaime

AU - Burzio, Verónica A.

AU - Belmar, Sebastián

AU - Araya, Mariela

AU - Jeldes, Emanuel

AU - Lobos-González, Lorena

AU - Silva, Verónica

AU - Villota, Claudio

AU - Oliveira-Cruz, Luciana

AU - Lopez, Constanza

AU - Socias, Teresa

AU - Castillo, Octavio

AU - Burzio, Luis O.

PY - 2017

Y1 - 2017

N2 - Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule. These studies showed inhibition of tumor growth and metastasis. Direct metastasis assessment by tail vein injection of RenCa cells also showed a drastic reduction in lung metastatic nodules. In vivo treatment reduces survivin, N-cadherin and P-cadherin levels, providing a molecular basis for metastasis inhibition. In consequence, the treatment significantly enhanced mouse survival in these models. Our results suggest that the ASncmtRNAs could be potent and selective targets for therapy against human renal cell carcinoma.

AB - Knockdown of antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptosis in several human and mouse tumor cell lines, but not normal cells, suggesting this approach for a selective therapy against different types of cancer. Here we show that in vitro knockdown of murine ASncmtRNAs induces apoptotic death of mouse renal adenocarcinoma RenCa cells, but not normal murine kidney epithelial cells. In a syngeneic subcutaneous RenCa model, treatment delayed and even reversed tumor growth. Since the subcutaneous model does not reflect the natural microenviroment of renal cancer, we used an orthotopic model of RenCa cells inoculated under the renal capsule. These studies showed inhibition of tumor growth and metastasis. Direct metastasis assessment by tail vein injection of RenCa cells also showed a drastic reduction in lung metastatic nodules. In vivo treatment reduces survivin, N-cadherin and P-cadherin levels, providing a molecular basis for metastasis inhibition. In consequence, the treatment significantly enhanced mouse survival in these models. Our results suggest that the ASncmtRNAs could be potent and selective targets for therapy against human renal cell carcinoma.

KW - Antisense therapy

KW - Mitochondria

KW - Murine renal cancer

KW - NcRNA

UR - http://www.scopus.com/inward/record.url?scp=85021828724&partnerID=8YFLogxK

U2 - 10.18632/oncotarget.18460

DO - 10.18632/oncotarget.18460

M3 - Article

VL - 8

SP - 43692

EP - 43708

JO - Oncotarget

JF - Oncotarget

SN - 1949-2553

IS - 27

ER -