Chemotherapie: Offener Zugang
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Abstrakt

CircDPY19L1P1/miR-130a-3p/PNPLA6 Axis: Regulating the Cell Differentiation in Acute Myeloid Leukemia (AML)

Ningze Xu, Ruye Ma, Huili Zhai, Houcai Wang

Objective: Acute Myeloid Leukemia (AML) is one of the most common aggressive hematological malignancies. circDPY19L1P1 have been demonstrated to present upregulation in AML patients. We attempted to elucidate molecular mechanism of circDPY19L1P1 underlying AML cell malignancy.

Methods: RT-qPCR evaluated circDPY19L1P1 level in AML bone marrow specimens and cells. RNase R digestion assay and actinomycin D evaluated circDPY19L1P1 circular characteristics in AML cells. FISH determined circDPY19L1P1 subcellular distribution in AML cells. Loss-of-function assays clarified circDPY19L1P1 role in AML cell behaviors. Bioinformatics and mechanism experiments assessed association of circDPY19L1P1 or PNPLA6 with miR-130a-3p in AML cells. Rescue assays assessed regulatory function of PNPLA6 in circDPY19L1P1-meidated AML cellular phenotypes.

Results: CircDPY19L1P1 presented upregulation and stable circular characteristics in AML cells. CircDPY19L1P1 silencing suppressed AML cell proliferation facilitated AML cell apoptosis and blocked AML cell differentiation. CircDPY19L1P1 served as a miR-130a-3p sponge to downregulate miR-130a-3p in AML cells. MiR-130a-3p targeted PNPLA6 3'UTR in AML cells and circDPY19L1P1 competitively bound to miR-130a-3p to upregulate PNPLA6. The influences of circDPY19L1P1 knockdown on AML cell proliferative ability, apoptosis and cell differentiation were countervailed by PNPLA6 elevation.

Conclusion: CircDPY19L1P1 presents upregulation and acts as an oncogene in AML cellular behaviors. CircDPY19L1P1 facilitates AML cell malignancy through serving as miR-513a-5p sponge to upregulate PNPLA6, which may provide a potential novel insight for therapeutic strategies of AML.