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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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    Immune-related IncRNA LINC00944 responds to variations in ADAR1 levels and it is associated with breast cancer prognosis
    (2021)
    Pamela R. de Santiago
    ;
    Alejandro Blanco
    ;
    Fernanda Morales
    ;
    Katherine Marcelain
    ;
    Olivier Harismendy
      2Scopus© Citations 38
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    Identification of Circulating lncRNAs Associated with Gallbladder Cancer Risk by Tissue-Based Preselection, Cis-eQTL Validation, and Analysis of Association with Genotype-Based Expression
    (2022)
    Alice Blandino
    ;
    Dominique Scherer
    ;
    Trine B. Rounge
    ;
    Sinan U. Umu
    ;
    Felix Boekstegers
    <jats:p>Long noncoding RNAs (lncRNAs) play key roles in cell processes and are good candidates for cancer risk prediction. Few studies have investigated the association between individual genotypes and lncRNA expression. Here we integrate three separate datasets with information on lncRNA expression only, both lncRNA expression and genotype, and genotype information only to identify circulating lncRNAs associated with the risk of gallbladder cancer (GBC) using robust linear and logistic regression techniques. In the first dataset, we preselect lncRNAs based on expression changes along the sequence “gallstones → dysplasia → GBC”. In the second dataset, we validate associations between genetic variants and serum expression levels of the preselected lncRNAs (cis-lncRNA-eQTLs) and build lncRNA expression prediction models. In the third dataset, we predict serum lncRNA expression based on individual genotypes and assess the association between genotype-based expression and GBC risk. AC084082.3 and LINC00662 showed increasing expression levels (p-value = 0.009), while C22orf34 expression decreased in the sequence from gallstones to GBC (p-value = 0.04). We identified and validated two cis-LINC00662-eQTLs (r2 = 0.26) and three cis-C22orf34-eQTLs (r2 = 0.24). Only LINC00662 showed a genotyped-based serum expression associated with GBC risk (OR = 1.25 per log2 expression unit, 95% CI 1.04–1.52, p-value = 0.02). Our results suggest that preselection of lncRNAs based on tissue samples and exploitation of cis-lncRNA-eQTLs may facilitate the identification of circulating noncoding RNAs linked to cancer risk.</jats:p>
      12Scopus© Citations 8
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      1  2Scopus© Citations 56
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    Identification and characterization of miRNAs and lncRNAs of coho salmon (Oncorhynchus kisutch) in normal immune organs.
    (2020)
    Francisco Leiva
    ;
    Marcelo Herrera
    ;
    Daniela Reyes
    ;
    Scarleth Bravo
    ;
    Killen Ko Garcia
    Scopus© Citations 19  3