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Author: search.filters.author.Luis O. BurzioHas files: No

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    Knockdown of Antisense Noncoding Mitochondrial RNA Reduces Tumorigenicity of Patient-Derived Clear Cell Renal Carcinoma Cells in an Orthotopic Xenograft Mouse Model
    (2024)
    Mariela Araya
    ;
    Francisca Sepúlveda
    ;
    Jaime Villegas
    ;
    Luis Alarcón
    ;
    Luis O. Burzio
    <jats:p>Clear cell renal cell carcinoma (ccRCC) is the most prevalent form of renal cancer and its treatment is hindered by a resistance to targeted therapies, immunotherapies and combinations of both. We have reported that the knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) with chemically modified antisense oligonucleotides induces proliferative arrest and apoptotic death in tumor cells from many human and mouse cancer types. These studies have been mostly performed in vitro and in vivo on commercially available cancer cell lines and have shown that in mouse models tumor growth is stunted by the treatment. The present work was performed on cells derived from primary and metastatic ccRCC tumors. We established primary cultures from primary and metastatic ccRCC tumors, which were subjected to knockdown of ASncmtRNAs in vitro and in vivo in an orthotopic xenograft model in NOD/SCID mice. We found that these primary ccRCC cells are affected in the same way as tumor cell lines and in the orthotopic model tumor growth was significantly reduced by the treatment. This study on patient-derived ccRCC tumor cells represents a model closer to actual patient ccRCC tumors and shows that knockdown of ASncmtRNAs poses a potential treatment option for these patients.</jats:p>
      1Scopus© Citations 6
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    Antisense noncoding mitochondrial RNA-2 gives rise to miR-4485-3p by Dicer processing in vitro
    (2021)
    Nicole Farfán
    ;
    Nicole Sanhueza
    ;
    Macarena Briones
    ;
    Luis O. Burzio
    ;
    Verónica A. Burzio
    <jats:title>Abstract</jats:title><jats:sec> <jats:title>Background</jats:title> <jats:p>The antisense noncoding mitochondrial RNAs (ASncmtRNAs) derive from the mitochondrial 16S gene. Knockdown of these transcripts with chemically-modified antisense oligonucleotides induces proliferative arrest, apoptosis and invasiveness reduction in tumor but not normal cells. One of these transcripts, ASncmtRNA-2, contains the complete and identical sequence of hsa-miR-4485-3p and, upon knockdown of this transcript, there is a strong increase in levels of this miRNA, suggesting ASncmtRNA-2 as a source for miR-4485-3p, which is supported by several evidences from our group and others, in the ex vivo setting.</jats:p> </jats:sec><jats:sec> <jats:title>Results</jats:title> <jats:p>Here we show that incubation of in vitro-transcribed ASncmtRNA-2 with recombinant Dicer produces RNA fragments corresponding to hsa-miR-4485-3p, showing that Dicer binds to and processes ASncmtRNA-2, strongly supporting the hypothesis that ASncmtRNA-2 acts as a precursor for miR-4485-3p.</jats:p> </jats:sec><jats:sec> <jats:title>Conclusion</jats:title> <jats:p>The in vitro results presented here strengthen the hypothesis that miR-4485-3p is derived from ASncmtRNA-2 by Dicer processing. Since miR-4485-3p is classified as a tumor suppressor miRNA, this evidence strengthens the application of ASncmtRNA knockdown for cancer therapy.</jats:p> </jats:sec>
    Scopus© Citations 5  1
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      1  2Scopus© Citations 56
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    Targeting antisense mitochondrial noncoding RNAs induces bladder cancer cell death and inhibition of tumor growth through reduction of survival and invasion factors
    (2020)
    Vincenzo Borgna
    ;
    Lorena González-sánchez
    ;
    Francisca Guevara
    ;
    Eduardo Landerer
    ;
    Maximiliano Bendek
      10Scopus© Citations 15