miR-342-3p Inhibits Acute Myeloid Leukemia Progression by Targeting SOX12
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY(2022)
摘要
Background. It is well known that microRNAs (miRNAs) interfere with the progression of various human malignancies. This article is aimed at exploring the regulating role of miR-342-3p in acute myeloid leukemia (AML) and its mechanism. Methods. We used the Gene Expression Omnibus (GEO) database to determine miR-342-3p differential expression patterns in AML patients' plasma and cells as well as healthy individuals' plasma and T cells. Quantitative real-time PCR and Western blotting were performed for plasma and cell miR-342-3p and SRY-related high-mobility-group box (SOX12) expression quantification, and cell counting kit-8 assay and flow cytometry were used for the determination of AML cell growth, cycle, and apoptosis. A dual-luciferase reporter gene assay was further carried out to identify the targeted association between miR-342-3p and SOX12 mRNA 3 ' UTR after prediction by a bioinformatics website. Pearson's correlation analysis was performed to analyze the connection between miR-342-3p and SOX12 expressions. The LinkedOmics database was utilized to explore the downstream pathways in which SOX12 was enriched. Results. Evidently downregulated plasma miR-342-3p and markedly elevated SOX12 were observed in AML patients versus healthy individuals. miR-342-3p mimics suppressed AML cell growth, enhanced apoptosis, and induced G0/G1 phase arrest; conversely, enhanced capacity of AML cells to proliferate, suppressed apoptosis, and accelerated cell cycle were observed after treatment with miR-342-3p inhibitors. SOX12 was confirmed as miR-342-3p's target gene. Overexpressing or knocking down SOX12 reversed miR-342-3p's impacts on AML cell growth, apoptosis, and cycle. Upregulated SOX12 was positively related to DNA replication and RNA polymerase signaling pathways. Conclusion. miR-342-3p affects apoptosis of AML cells and their ability to proliferate via targeted regulation of SOX12.
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关键词
acute myeloid leukemia,sox12
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