• Eur. J. Clin. Invest. · Aug 2021

    High-mobility group AT-hook 2 promotes growth and metastasis and is regulated by miR-204-5p in oesophageal squamous cell carcinoma.

    • Hongdian Zhang, Xianxian Wu, Zhilin Sui, Zhao Ma, Lei Gong, Bin Meng, Peng Tang, and Zhentao Yu.
    • Department of Esophageal Cancer, Tianjin Medical University Cancer Institute and Hospital, Key Laboratory of Cancer Prevention and Therapy of Tianjin, Tianjin's Clinical Research Center for Cancer, National Clinical Research Center of Cancer, Tianjin, China.
    • Eur. J. Clin. Invest. 2021 Aug 1; 51 (8): e13563.

    BackgroundTo investigate the expression of high-mobility group AT-hook 2 (HMGA2) and miR-204-5p in oesophageal squamous cell carcinoma (ESCC) and their biological roles in ESCC development and progression.MethodsHMGA2 and miR-204-5p expression levels in ESCC tissues and cell lines were detected by qRT-PCR, Western blotting and immunohistochemical staining. ESCC cell lines were transfected with a small interfering RNA for HMGA2 and miR-204-5p mimic to downregulate and upregulate the expression levels of HMGA2 and miR-204-5p, respectively. The growth, migration and invasion abilities of ESCC cells were assessed by MTT, colony formation, wound-healing and Transwell assays, respectively. A luciferase reporter gene assay was used to determine whether the 3'-untranslated coding regions of HMGA2 could be directly bound by miR-204-5p.ResultsHMGA2 expression was markedly upregulated (P < .001), while miR-204-5p expression was markedly downregulated (P = .003) in ESCC tissues compared with adjacent normal tissues. HMGA2 expression was correlated with tumour size, invasion depth, lymph node metastasis and tumour-node-metastasis stage (all P < .05) and was identified as an independent prognostic factor for ESCC patients. The expression levels of HMGA2 and miR-204-5p were negatively correlated (r2  = 0.609, P < .001). HMGA2 knockdown or miR-204-5p overexpression markedly inhibited ESCC cell growth, migration and invasion (P < .05). In addition, restoration of HMGA2 expression partly reversed the inhibitory effects of miR-204-5p overexpression on migration and invasion (P < .05). The luciferase reporter gene assay suggested that HMGA2 is a direct downstream target of miR-204-5p.ConclusionHMGA2 functions as an oncogene in the growth and metastasis of ESCC and is negatively regulated by miR-204-5p.© 2021 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.

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