Knockout of DROSHA Increases the Sensitivity of HCT116 Cells to Apoptosis in Response to Actinomycin-D Treatment
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MicroRNAs are short non-coding RNAs that function as sequence-directed post-transcriptional inhibitors of gene expression. The cellular response to ten drugs including actinomycin-D (ACT-D) was examined in a genetically modified HCT116 colon cancer cell line with a deletion in the gene encoding a critical miRNA processing enzyme called DROSHA. We found that the DROSHA-null subline was more susceptible than the parental cells expressing wild-type DROSHA to apoptosis induced by several drugs, most prominently ACT-D. This increase in susceptibility to apoptosis was characterized by increased DNA-fragmentation, increased caspase-3/7 activity, and loss of membrane integrity. The increased susceptibility to apoptosis was not associated with differences in DNA-synthesis, RNA-synthesis, protein-synthesis, metabolic activity, p53 response or the induction of replicative-senescence. Our results suggest that these cell lines are equally sensitive to the direct effects of ACT-D but these DROSHA-null cells are more sensitive to apoptosis induced by a subset of drugs exemplified by ACT-D.
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Copyright © 2022 the author(s). Theses may be used for non-commercial research, educational, or related academic purposes only. Such uses include personal study, research, scholarship, and teaching. Theses may only be shared by linking to Carleton University Institutional Repository and no part may be used without proper attribution to the author. No part may be used for commercial purposes directly or indirectly via a for-profit platform; no adaptation or derivative works are permitted without consent from the copyright owner.
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