Background: Zinc finger protein 667-antisense RNA 1 (ZNF667-AS1), a long non-coding RNA (lncRNA), plays important parts in tumorigenesis and development of esophageal squamous cell carcinoma, but its function in acute myeloid leukemia (AML) is unknown. Our goal here was to probe the functional mechanism of ZNF667-AS1 in AML by mediating microRNA-206 (miR-206)/A-kinase anchoring protein 13 (AKAP13) axis. Materials and Methods: The bone marrow samples from AML patients and controls were selected for microarray analysis to select significantly upregulated lncRNAs. Next, effects of ZNF667-AS1 on cell aggressiveness of AML were assessed after delivery of cells with siRNA against ZNF667-AS1. Subcellular fractionation location assay and FISH experiments were used to determine ZNF667-AS1 localization in cells. Dual-luciferase experiments detect the targeting relationships among ZNF667-AS1, miR-206 and AKAP13. Finally, tumor growth and metastasis were evaluated in vivo to determine the relevance of ZNF667-AS1/ miR-206/AKAP13 axis. Results: The expression of ZNF667-AS1 was upregulated in AML patients, which predicted poor prognosis. Downregulation of ZNF667-AS1 reduced cell proliferation, invasion, tumori-genesis and metastasis. miR-206 inhibitor reversed the repressive role of ZNF667-AS1 knock-down in cell proliferation, invasion and tumorigenesis, while AKAP13 silencing flattened the stimulative role of miR-206 inhibitor in AML malignant aggressiveness. Mechanistically, we demonstrated that ZNF667-AS1 functioned as a molecular sponge for miR-206. In addition, we observed that Wnt/β-catenin pathway was suppressed by ZNF667-AS1 knockdown. Conclusion: ZNF667-AS1 potentiated AML progression by targeting the miR-206/AKAP13 axis. This indicates ZNF667-AS1 inhibition may act as a prospective therapeutic option for the treatment of AML.
CITATION STYLE
Wang, N., Feng, Y., Xie, J., Han, H., Dong, Q., & Wang, W. (2020). Long non-coding RNA ZNF667-AS1 knockdown curbs liver metastasis in acute myeloid leukemia by regulating the microRNA-206/AKAP13 axis. Cancer Management and Research, 12, 13285–13300. https://doi.org/10.2147/CMAR.S269258
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