LncRNA ZEB2-AS1 promotes the proliferation, migration and invasion of esophageal squamous cell carcinoma cell through miR-574-3p/HMGA2 axis

J.-H. Xu, R.-Z. Chen, L.-Y. Liu, X.-M. Li, C.-P. Wu, Y.-T. Zhou, J.-D. Yan, Z.-Y. Zhang

Department of Pathology, Tangshan Gongren Hospital, Tangshan, Hebei, China. linzhao48036@163.com

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• Oncology

OBJECTIVE: Esophageal squamous cell carcinoma (ESCC) is a common malignant epithelial tumor in the elderly, and the cause is very complicated. Therefore, the study of the pathogenesis of ESCC is conducive to the effective treatment of ESCC. Many studies indicated that lncRNAs were important regulatory factors in tumor formation and disease development. However, the regulatory network of lncRNA in ESCC has not been fully explored.

MATERIALS AND METHODS: The expression of miR-574-3p, ZEB2-AS1, and HMGA2 was measured using qRT-PCR. The protein expression of PCNA, Cleaved-caspase3, MMP9, and HMGA2 was detected through Western blot. Cell proliferation or apoptosis of transfected cells was calculated via CKK-8 assay or flow cytometry. Transwell assay was applied to detect cell migration and invasion of ESCC cells. Luciferase reporter assay and RNA pull-down were used to determine the relationship among miR-574-3p, ZEB2-AS1, and HMGA2 in ESCC. Moreover, the regulatory network of ZEB2-AS1 has been verified in vivo in this study.

RESULTS: We found that ZEB2-AS1 was upregulated in ESCC tissues and cells. The knockdown of ZEB2-AS1 could inhibit cell proliferation, invasion, and migration, as well as promoted cell apoptosis in ESCC. Interestingly, miR-574-3p deficiency or HMGA2 promotion could reverse the effects of si-ZEB2-AS1 on ESCC cell progression. Luciferase reporter assay indicated that miR-574-3p was a target miRNA of ZEB2-AS1 and HMGA2 was a target gene of miR-574-3p in ESCC.

CONCLUSIONS: In this paper, we first verified the novel regulatory mechanism of lncRNA ZEB2-AS1 in ESCC cellular process. LncRNA ZEB2-AS1 promoted the proliferation, migration, and invasion of ESCC by modulating miR-574-3p/HMGA2 axis, indicating that ZEB2-AS1 played essential roles in cell progression in ESCC and providing a new therapeutic target of ESCC.

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