A comprehensive in vivo screen for anti-apoptotic miRNAs indicates broad capacities for oncogenic synergy Journal Article


Authors: Bejarano, F.; Chang, C. H.; Sun, K.; Hagen, J. W.; Deng, W. M.; Lai, E. C.
Article Title: A comprehensive in vivo screen for anti-apoptotic miRNAs indicates broad capacities for oncogenic synergy
Abstract: microRNAs (miRNAs) are ~21–22 nucleotide (nt) RNAs that mediate broad post-transcriptional regulatory networks. However, genetic analyses have shown that the phenotypic consequences of deleting individual miRNAs are generally far less overt compared to their misexpression. This suggests that miRNA deregulation may have broader phenotypic impacts during disease situations. We explored this concept in the Drosophila eye, by screening for miRNAs whose misexpression could modify the activity of pro-apoptotic factors. Via unbiased and comprehensive in vivo phenotypic assays, we identify an unexpectedly large set of miRNA hits that can suppress the action of pro-apoptotic genes hid and grim. We utilize secondary assays to validate that a subset of these miRNAs can inhibit irradiation-induced cell death. Since cancer cells might seek to evade apoptosis pathways, we modeled this situation by asking whether activation of anti-apoptotic miRNAs could serve as “second hits”. Indeed, while clones of the lethal giant larvae (lgl) tumor suppressor are normally eliminated during larval development, we find that diverse anti-apoptotic miRNAs mediate the survival of lgl mutant clones in third instar larvae. Notably, while certain anti-apoptotic miRNAs can target apoptotic factors, most of our screen hits lack obvious targets in the core apoptosis machinery. These data highlight how a genetic approach can reveal distinct and powerful activities of miRNAs in vivo, including unexpected functional synergies during disease or cancer-relevant settings. © 2021
Keywords: apoptosis; microrna; drosophila; tumor suppressor; eye; genetic screen
Journal Title: Developmental Biology
Volume: 475
ISSN: 0012-1606
Publisher: Elsevier Inc.  
Date Published: 2021-07-01
Start Page: 10
End Page: 20
Language: English
DOI: 10.1016/j.ydbio.2021.02.010
PROVIDER: scopus
PUBMED: 33662357
PMCID: PMC8107139
DOI/URL:
Notes: Article -- Export Date: 1 April 2021 -- Source: Scopus
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  1. Eric C Lai
    159 Lai
  2. Joshua W Hagen
    7 Hagen
  3. Kailiang Sun
    6 Sun