HIPK3 Promotes Growth and Metastasis of Esophageal Squamous Cell Carcinoma via Regulation of miR-599/c-MYC Axis

HIPK3通过调控miR-599/c-MYC轴促进食管鳞状细胞癌的生长和转移

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Abstract

BACKGROUND/AIMS: this experimental design was based on HIPK3 to explore the pathogenesis of ESCC. METHODS: RT-qPCR was used to detect the expression of CircHIPK3 and miR-599 in ESCC tissues and cell lines.CCK-8, colony formation, flow cytometry and transwell assay were used to detect the effects of CircHIPK3 and miR-599 on tumor cell proliferation, apoptosis and migration and invasion. Target gene prediction and screening, luciferase reporter assays were used to validate downstream target genes of CircHIPK3 and miR-599.mRNA and protein expression of c-MYC were detected by RT-qPCR and Western blotting. The tumor changes in mice were detected by in vivo experiments in nude mice. RESULTS: HIPK3 was highly expressed in ESCC tissues and cell lines. In addition, HIPK3 expression levels were associated with advanced TNM stage, lymph node metastasis and tumor size. Moreover, HIPK3 was significantly promoted cell proliferation and migration of ESCC cells. In addition, HIPK3 was able to inhibit miRNA-599 expression and up-regulate the expression level of c-MYC. Finally, the results of in vivo animal models confirmed that HIPK3 promoted ESCC progression by modulating the miR-599/c-MYC axis. CONCLUSION: HIPK3 can regulate the proliferation of esophageal squamous cell carcinoma cells by regulating miR-599/c-MYC axis, thereby inhibiting the occurrence and development of esophageal squamous cell carcinoma.

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