Wang Nan, Feng Yanping, Xie Jinye, Han Hui, Dong Qian, Wang Weijia
Laboratory Diagnosis Center, Zhongshan People's Hospital, Zhongshan, 528403 Guangdong, People's Republic of China.
Cancer Manag Res. 2020 Dec 23;12:13285-13300. doi: 10.2147/CMAR.S269258. eCollection 2020.
Zinc finger protein 667-antisense RNA 1 (), 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 in AML by mediating microRNA-206 ()/A-kinase anchoring protein 13 () axis.
The bone marrow samples from AML patients and controls were selected for microarray analysis to select significantly upregulated lncRNAs. Next, effects of on cell aggressiveness of AML were assessed after delivery of cells with siRNA against . Subcellular fractionation location assay and FISH experiments were used to determine localization in cells. Dual-luciferase experiments detect the targeting relationships among , and . Finally, tumor growth and metastasis were evaluated in vivo to determine the relevance of / axis.
The expression of was upregulated in AML patients, which predicted poor prognosis. Downregulation of reduced cell proliferation, invasion, tumorigenesis and metastasis. 6 inhibitor reversed the repressive role of knockdown in cell proliferation, invasion and tumorigenesis, while silencing flattened the stimulative role of inhibitor in AML malignant aggressiveness. Mechanistically, we demonstrated that functioned as a molecular sponge for . In addition, we observed that Wnt/β-catenin pathway was suppressed by knockdown.
potentiated AML progression by targeting the / axis. This indicates inhibition may act as a prospective therapeutic option for the treatment of AML.
锌指蛋白667反义RNA1（）是一种长链非编码RNA（lncRNA），在食管鳞状细胞癌的肿瘤发生和发展中起重要作用，但其在急性髓系白血病（AML）中的功能尚不清楚。我们的目标是通过介导微小RNA-206（）/A激酶锚定蛋白13（）轴来探究在AML中的功能机制。
选取AML患者和对照组的骨髓样本进行微阵列分析，以筛选出显著上调的lncRNAs。接下来，在用针对的小干扰RNA转染细胞后，评估对AML细胞侵袭性的影响。采用亚细胞分级定位分析和荧光原位杂交实验来确定在细胞中的定位。双荧光素酶实验检测、和之间的靶向关系。最后，在体内评估肿瘤生长和转移情况，以确定/轴的相关性。
在AML患者中表达上调，这预示着预后不良。下调可降低细胞增殖、侵袭、肿瘤发生和转移。6抑制剂可逆转敲低对细胞增殖、侵袭和肿瘤发生的抑制作用，而沉默则可消除抑制剂对AML恶性侵袭性的促进作用。机制上，我们证明可作为的分子海绵发挥作用。此外，我们观察到敲低可抑制Wnt/β-连环蛋白通路。
通过靶向/轴促进AML进展。这表明抑制可能是治疗AML的一种潜在治疗选择。
