4.6 Article

miR-148a-3p and DDX6 functional link promotes survival of myeloid leukemia cells

Journal

BLOOD ADVANCES
Volume 7, Issue 15, Pages 3846-3861

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ELSEVIER
DOI: 10.1182/bloodadvances.2022008123

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Regulation of gene expression at the RNA level plays a crucial role in cancer. However, the posttranscriptional pathways involved in tumor formation are still not well understood. In this study, researchers identified a functional pathway involving miR-148a-3p, RNA helicase DDX6, and the downstream target TXNIP in acute myeloid leukemia (AML). The depletion of DDX6 led to cell cycle arrest, apoptosis, and differentiation, delaying leukemia development. This study highlights the potential therapeutic target of the regulatory link between miR-148a-3p and DDX6 in leukemia treatment.
Regulation of gene expression at the RNA level is an important regulatory mechanism in cancer. However, posttranscriptional molecular pathways underlying tumorigenesis remain largely unexplored. In this study, we uncovered a functional axis consisting of microRNA (miR)-148a-3p, RNA helicase DDX6, and its downstream target thioredoxininteracting protein (TXNIP) in acute myeloid leukemia (AML). Using a DROSHA-knockout cell system to evaluate miR-mediated gene expression control, we comprehensively profiled putative transcripts regulated by miR-148a-3p and identified DDX6 as a direct target of miR148a-3p in AML cells. DDX6 depletion induced cell cycle arrest, apoptosis, and differentiation, although delaying leukemia development in vivo. Genome-wide assessment of DDX6-binding transcripts and gene expression profiling of DDX6-depleted cells revealed TXNIP, a tumor suppressor, as the functional downstream target of DDX6. Overall, our study identified DDX6 as a posttranscriptional regulator that is required for AML survival. We proposed the regulatory link between miR-148a-3p and DDX6 as a potential therapeutic target in leukemia.

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