Long Non-Coding RNA ZNF667-AS1 Knockdown Curbs Liver Metastasis in Acute Myeloid Leukemia by Regulating the microRNA-206/AKAP13 Axis
Authors: Hui Han
Nan Wang
Weijia Wang
Qian Dong
Yanping Feng
Jinye Xie
Journal: Cancer Management and Research (2020)
Discipline: CLINICAL MEDICINE
Keywords: AKAP13; acute myeloid leukemia; long non-coding RNA ZNF667-AS1; microRNA-206.
Affiliations: Laboratory Diagnosis Center, Zhongshan People's Hospital, Zhongshan, 528403 Guangdong, People's Republic of China.

Abstract:  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-206 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 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-AS 1 inhibition may act as a prospective therapeutic option for the treatment of AML. 

Retracted: No

PubPeer comments:
 As noted on other threads, what appear to be the same tumors (and transformations of them) appear in three papers by unrelated groups of researchers: - Fig 4F from [Liu et al (2019)] . - Fig 7C from [Shi et al (2020)] . - Fig 5C from [Wen et al (2021)] . ![] ![] Here I am interested in the **ruler**, which migrated around the institutions along with the tumors. Note its distinctive markings: on the 10 , a stain at the tip of the leftward stroke of the 1 , and a stain in the middle of the righthand curve of the 0 . On the 20 , a stain along the tops of both digits. The ruler continued its travels and we find it in Fig 6A of [Ji Shang (2020)] ,  Effects of RPL38 knockdown on the size of MKN-45 xenograft tumors in nude mice. ![file] Fig 7A of [Liu et al (2020)] .  Tumors in nude mice after tumorigenesis . ![file] **Figs 3C, 5E, 7F of [Wang et al (2020)] **.  Tumor volume and tumor weight in mice . ![file] In Fig 4B of [Zhao et al (2020)] ,  Tumor weight was determined in the isolated tumors from the nude mice , the resolution is lower but the 20 seems to display the same stain. ![file] The same low-resolution caveat applies to Fig 8B of [Xu et al (2020)] ,  Tumor weight was increased after miR-483-3p overexpression . ![file] It would make sense if the xenograft experiments were all the work of a single laboratory, but none of the papers mention outsourcing any research to an outside agency. , 
 - *[above]* Figs 5G, 7F. Two panels overlap and are unlikely to represent different treatments, - *[below]* Fig 5d from  MicroRNA-520a Suppresses Pathogenesis and Progression of NonSmall-Cell Lung Cancer through Targeting the RRM2 Wnt Axis ([Xie et al 2021] ). Another overlap. ![file] ,