A Synthetic Sponge System Against miRNAs of the miR-17/92 Cluster Targets Transcriptional MYC Dosage Compensation in Aneuploid Cancer.

ABSTRACT:

Background

Genomic instability, a hallmark of cancer, leads to copy number variations disrupting gene dosage balance and contributing to tumor progression. One of the most affected oncogenes is MYC, whose overexpression is tightly regulated to avoid cytotoxicity. In aneuploid cancer cells, gene dosage compensation mechanisms involving microRNAs (miRNAs) from the miR-17/92 cluster contribute in regulating MYC expression. Targeting this miRNA-mediated compensation system represents a promising therapeutic strategy leading to an uncontrolled and lethal MYC overexpression.

Results

Synthetic miRNA sponges targeting miR-17, miR-19a, and miR-20a, key regulators of MYC dosage compensation, were designed and validated. Breast cancer cells (MCF7) with stable exogenous MYC overexpressi

SUBMITTER: Bravo-Estupinan DM 

PROVIDER: S-EPMC12427730 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature