ABSTRACTThe study was designed to explore
the role of PSMA3-AS1 in initiation and progression of acute myeloid leukemia
(AML) and investigate its action mechanism. Expression
of PSMA3-AS1, miR-20a-5p and ATG16L1 bothin
vitroandin vivowas measured by
qRT-PCR. The expression of protein
was detected by western blot assay. Edu staining and flow cytometry were utilized
to measure cell proliferation and apoptosis. Potential target was predicted by
bioinformatics and was verified by dual-luciferase report gene assay and RNA
pull down assay. QRT-PCR was used to quantify autophagy (LC3, Beclin1, P62)
related genes. The m6A modification test is used to verify the effect of METTL3
on PSMA3-AS1. Tumor model was used to identify the
effect of PSMA3-AS1 on tumor growthin
vivo, and immunohistochemistry was applied to detect expression of ki67 and
TUNEL. The
results indicate that PSMA3-AS1 was upregulated in FLT3-ITD+
AML patients. Si-PSMA3-AS1 could inhibit the
proliferation, autophagy and promote the apoptosis in MV4-11 and Molm13 cells. METTL3 could enhance the PSMA3-AS1 RNA stability. In addition, this study
revealed that PSMA3-AS1 affected FLT3-ITD+ AML by
targeting expression of miR-20a-5p, and miR-20a-5p further modulated expression
of ATG16L1, an mRNA that down-regulated in AML, to affect disease advancement. PSMA3-AS1 could promote FLT3-ITD+
AML progression by regulating the level of autophagy through miR-20a-5p/ATG16L1
pathway. In addition, the increase of PSMA3-AS1 may be caused by the
involvement of METTL3 in regulating its stability. This discovery will provide
new horizons for early screening and targeted therapy of FLT3-ITD+ AML.