Long Non-Coding RNA ZNF667-AS1 Knockdown Curbs Liver Metastasis in Acute Myeloid Leukemia by Regulating the microRNA-206/AKAP13 Axis

作者：Nan Wang, Yanping Feng, Jinye Xie, Hui Han, Qian Dong, Weijia Wang · 发表于：Cancer Management and Research · 年份：2020 · DOI：10.2147/cmar.s269258 · 被引用次数：15 · 研究领域：Cancer-related molecular mechanisms research、Acute Myeloid Leukemia Research、RNA modifications and cancer

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, tumorigenesis and metastasis. miR-20 6 inhibitor reversed the repressive role of ZNF667-AS1 knockdown in cell proliferation, invasion and tumorigenesis, while AKAP13 silencing flattened the stimulative role of miR-206 inhibitor in AML malignant aggressiveness. Mechanistically, we d...