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.

Long noncoding RNAs: A novel insight in the leukemogenesis and drug resistance in acute myeloid leukemia

“…Mechanistically, ZEB2‐AS1 displayed an inverse relationship between miR‐122‐5p and PLK1. Moreover, ZEB2‐AS1 has been found to control PLK1 protein expression by acting as a sponge for miR‐122‐5p in AML cells (Guan et al, 2020). Interestingly, higher CASC15 was reported to enhance apoptosis associated with myeloid differentiation, leading to a decrease in the engraftment of primary bone marrow cells, thereby confirming the antileukemic potential of CASC15 (Fernando et al, 2017).…”

Circular RNA ZNF609 promotes the malignant progression of glioma by regulating miR-1224-3p/PLK1 signaling

“…PLK1 plays multiple roles in the biological progression, including cell division, cell cycle, cell growth and metastasis 38 , 39 . PLK1 has been verified to be involved in various cancers, such as hepatocellular carcinoma 40 , breast cancer 41 , prostate cancer 42 , acute myeloid leukemia 43 . Additionally, PLK1 has been reported to be upregulated in glioma and can markedly promote cell proliferation and migration 44 - 46 .…”

Zeb2 DNA-binding sites in neuroprogenitor cells reveal autoregulation and affirm neurodevelopmental defects, including in Mowat-Wilson Syndrome

“…This is concluded from transgenic Zeb2 cDNA-based rescues in Zeb2 -KO ESCs and similar genetic rescues in Zeb2 -mutant cells in mice, which can via heterozygous/homozygous combinations create an elegant and large panel of Zeb2 levels (in interneurons (36), NK cells (67), ESCs (25)). Another illustration of the relevance of fine-tuned control of Zeb2 levels are miRs targeting Zeb2, and lncRNAs that regulate these miRs (68–71), with Zeb2 on its turn also controlling some of its own miR-encoding genes or clusters (72–74). In our ChIP-seq we find 125 peaks (∼5% of the total) that correspond to the TSSs of 98 miR-genes (File S1).…”