Ba Yufeng, Liu Yining, Li Changsheng, Zhu Yu, Xing Wenqun
Department of Thoracic Surgery, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450008, People's Republic of China.
Department of Medical Records, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou City, Henan Province 450008, People's Republic of China.
Onco Targets Ther. 2020 Mar 6;13:1967-1978. doi: 10.2147/OTT.S217087. eCollection 2020.
BACKGROUND/AIMS: this experimental design was based on HIPK3 to explore the pathogenesis of ESCC.
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.
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.
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.
背景/目的:本实验设计基于HIPK3来探究食管鳞状细胞癌(ESCC)的发病机制。
采用RT-qPCR检测ESCC组织和细胞系中CircHIPK3和miR-599的表达。运用CCK-8、集落形成、流式细胞术和Transwell实验检测CircHIPK3和miR-599对肿瘤细胞增殖、凋亡、迁移和侵袭的影响。通过靶基因预测与筛选、荧光素酶报告基因实验验证CircHIPK3和miR-599的下游靶基因。采用RT-qPCR和蛋白质免疫印迹法检测c-MYC的mRNA和蛋白表达。通过裸鼠体内实验检测小鼠的肿瘤变化。
HIPK3在ESCC组织和细胞系中高表达。此外,HIPK3表达水平与TNM晚期、淋巴结转移和肿瘤大小相关。而且,HIPK3显著促进ESCC细胞的增殖和迁移。此外,HIPK3能够抑制miRNA-599表达并上调c-MYC的表达水平。最后,体内动物模型结果证实HIPK3通过调节miR-599/c-MYC轴促进ESCC进展。
HIPK3可通过调节miR-599/c-MYC轴调控食管鳞状细胞癌细胞的增殖,从而抑制食管鳞状细胞癌的发生和发展。