Abstract |
Acute myeloid leukemia (AML) is an aggressive hematological malignancy with poor long-term outcomes. Numerous studies claim that circular RNAs ( circRNAs) are important regulators in AML progression. This study intended to explore the role of circNPM1 in AML development and drug chemoresistance. The expression of circNPM1 and miR-345-5p was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cellular activities, including cell growth, apoptosis, cell cycle, migration and invasion, were monitored using colony formation assay, flow cytometry assay and transwell assay, respectively. The relationship between miR-345-5p and circNPM1 or Frizzled-5 (FZD5) was predicted by the bioinformatics tool starBase and validated by dual- luciferase reporter assay or RNA immunoprecipitation (RIP) assay. CircNPM1 was abundantly expressed in serum samples from AML patients and AML cell lines. CircNPM1 silence or miR-345-5p restoration repressed colony formation, cell migration and invasion, contributed to cell apoptosis and cell cycle arrest, and weakened Adriamycin (ADM) resistance of AML cells. MiR-345-5p was a target of circNPM1 and was downregulated in AML serum and cells. MiR-345-5p deficiency reversed the effects of circNPM1 silence. Further, FZD5 was targeted by miR-345-5p, and circNPM1 regulated FZD5 expression by adsorbing miR-345-5p. FZD5 overexpression could block the function of miR-345-5p restoration. CircNPM1 might be a vital regulator for ADM chemoresistance in AML cells, which partly depended on the role of the miR-345-5p/FZD5 axis. Our study presents the view that circNPM1 degradation may be a key strategy in AML resistance therapy.
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Authors | Jie Ding, Xiaochun Zhang, Jianan Xue, Le Fang, Chunmei Ban, Bin Song, Lili Wu |
Journal | Central-European journal of immunology
(Cent Eur J Immunol)
Vol. 46
Issue 2
Pg. 162-182
( 2021)
ISSN: 1426-3912 [Print] Poland |
PMID | 34764785
(Publication Type: Journal Article)
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