Antisense LNA GapmeR targeting hsa-piR-33195 induces antiproliferative and apoptotic effects on human acute myeloid leukemia.

Abstract

Acute myeloid leukemia (AML) is a severe hematologic malignancy caused by the rapid proliferation of myeloid progenitor cells in the bone marrow. Non-coding RNAs, particularly, PIWI-interacting RNAs (piRNAs), play a role in the development of several cancers. Hsa-piR-33195, in particular, may promote AML development since its levels are substantially higher in AML patients. This study explores its anticancer effects and molecular mechanisms in AML cells in vitro. Human AML bone marrow blast cells and KG1 cells were transfected with piR-33195 locked nucleic acid antisense (LNA) GapmeRs 24, 48, and 72 hours after transfection. The transfection efficiency was then assessed using a fluorescent microscope. After that, qRT-PCR was used to measure piR-33195, CASP3, and CASP9. MTT was employed to evaluate the growth and viability of treated cells. Finally, the therapeutic effect of the antisense LNA GapmeRs on cell apoptosis and necrosis was assessed using Annexin V/PI staining. Bioinformatics analyses were conducted to predict the piR-33195 target genes in AML. Findings demonstrated a significant decrease in piR-33195, as well as increased CASP3 and CASP9 expression, in bone marrow samples from AML patients and the KG1 cell line, 24, 48, and 72 hours after transfection with antisense LNA Gamers. Moreover, suppressing piR-33195 markedly reduced cell growth in the transfected cells. Apoptosis and necrosis were significantly elevated in these cells. Bioinformatics identified gene and pathways associated with apoptosis and PI3K-AKT signaling. Inhibiting piR-33195 may be a promising treatment option for AML with fewer adverse effects.