Long non-coding RNA ZEB2-AS1 affects cell proliferation and apoptosis via the miR-122-5p/PLK1 axis in acute myeloid leukemia

Abstract

Acute myeloid leukemia (AML) is a highly heterogeneous disease featured by the clonal accumulation of immature myeloid cells. Zinc finger E-box binding homeobox 2 (ZEB2)-antisense RNA 1 (AS1) has been verified to participate in the progression of several types of cancer, including AML. However, the potential mechanisms of ZEB2-AS1 in AML have not yet been fully elucidated. The present study aimed to elucidate the role and regulatory mechanisms of ZEB2-AS1 in AML. The expression of ZEB2-AS1, microRNA-122-5p (miRNA/miR-122-5p) and polo-like kinase 1 (PLK1) was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) in AML tissues or cells. Cell proliferation and apoptosis were examined by methyl thiazolyl tetrazolium (MTT) assay and apoptosis assay, respectively. The protein levels were examined by western blot analysis. The targeted sequence between miR-122-5p and ZEB2-AS1 or PLK1 was predicted using an online database and verified by dual-luciferase reporter assay. A mouse tumor xenograft model was established to confirm the effects of ZEB2-AS1 on tumor growth in vivo. The results revealed that the expression levels of ZEB2-AS1 and PLK1 were upregulated, while those of miR-122-5p were downregulated in AML tissues and cells. The knockdown of ZEB2-AS1 inhibited proliferation and induced apoptosis in vitro, and inhibited tumor growth in vivo. By experimental verification, ZEB2-AS1 was found to negatively regulate miR-122-5p expression and PLK1 was found to be a target gene of miR-122-5p. Furthermore, ZEB2-AS1 was verified to regulate the expression of PLK1 by sponging miR-122-5p in AML cells. On the whole, the findings of the present study demonstrate that ZEB2-AS1 promotes cell proliferation and inhibits apoptosis, at least partly by targeting PLK1 mediated by miR-122-5p in AML cells.