AI Article Synopsis
- MicroRNAs (miRNAs) regulate gene expression by either degrading or inhibiting the translation of specific mRNAs, and their interactions can explain indirect relationships among different mRNAs in the body.
- Current research suggests that the involvement of the proteins produced from these targeted mRNAs has not been adequately examined in the competition dynamics of competing endogenous RNA (ceRNA) networks.
- A new deterministic model indicates that significant changes in the levels of mRNAs targeted by miRNAs also depend on the transcriptional inhibition of miRNAs by those target proteins, especially observed in ovarian cancer scenarios where miR-193a's epigenetic silencing by E2F6 is crucial for altering the levels of c-KIT and PBX1 associated with
Article Abstract
MicroRNAs (miRNAs) play an important role in gene regulation by degradation or translational inhibition of the targeted mRNAs. It has been experimentally shown that the way miRNAs interact with their targets can be used to explain the indirect interactions among their targets, i.e., competing endogenous RNA (ceRNA). However, whether the protein translated from the targeted mRNAs can play any role in this ceRNA network has not been explored. Here we propose a deterministic model to demonstrate that in a network of one miRNA interacting with multiple-targeted mRNAs, the competition between miRNA-targeted mRNAs is not sufficient for the significant change of those targeted mRNA levels, while dramatic changes of these miRNA-targeted mRNAs require transcriptional inhibition of miRNA by its target proteins. When applied to estrogen receptor signaling pathways, the miR-193a targets E2F6 (a target of estrogen receptor), c-KIT (a marker for cancer stemness), and PBX1 (a transcriptional activator for immunosuppressive cytokine, IL-10) in ovarian cancer, such that epigenetic silencing of miR-193a by E2F6 protein is required for the significant change of c-KIT and PBX1 mRNA level for cancer stemness and immunoevasion, respectively, in ovarian cancer carcinogenesis.
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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8876507 | PMC |
| http://dx.doi.org/10.3390/ijms23042277 | DOI Listing |
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