Objective: To investigate the function and mechanism of zinc finger protein 750 (ZNF750) in esophageal squamous cell carcinoma (ESCC). Methods: Xenograft in nude mice was applied to detect the tumorigenesis of ZNF750-depleted ESCC cells. Western blot was performed to observe the expression of downstream target protein of ZNF750 in ESCC cell lines and xenograft tumor tissues in which ZNF750 was knocked down. 3-(4, 5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H tetrazolium bromide (MTT) assay was used to determine the proliferation of ZNF750 stably depleted cells after restoration of its target protein. Results: The tumor weight of blank control, negative control and ZNF750 knockdown groups was 137±26 mg, 161±31 mg and 463±89 mg, respectively, with a statistically significant difference (P<0.01). The expressions of Kruppel-like factor 4 (KLF4) in ZNF750-depleted ESCC cells and its derived tumor tissue xenograft in nude mice were significantly down-regulated. Restoration of KLF4 in ZNF750 stably depleted cells significantly inhibited the cell proliferation (P<0.01). Conclusions: ZNF750 may be a new tumor suppressor in the tumorigenesis of ESCC, and the inhibition of cell proliferation induced by ZNF750 may be partially through the regulation of KLF4 expression.
目的： 探讨锌指蛋白750(ZNF750)在食管鳞癌中的作用及相关机制。 方法： 裸鼠体外成瘤实验分析ZNF750敲除后对食管鳞癌细胞成瘤能力的影响，Western blot检测敲除ZNF750基因的食管鳞癌细胞株和裸鼠移植瘤中下游靶基因的表达情况，四甲基偶氮唑蓝法检测ZNF750敲除后，导入下游基因对细胞增殖的影响。 结果： 空白对照组、非特异序列组和ZNF750敲除组的肿瘤重量分别为(137±26)mg、(161±31)mg和(463±89)mg，差异有统计学意义 (P<0.01)。敲除ZNF750基因的食管鳞癌细胞株及ZNF750敲除组的裸鼠移植瘤组织中，KLF4蛋白的表达均明显下调。在稳定敲除ZNF750的食管鳞癌细胞中导入KLF4基因，细胞的增殖能力降低(P<0.01)。 结论： ZNF750基因可能是与食管鳞癌发生密切相关的新的肿瘤抑制基因，其可能通过调节KLF4的表达抑制食管癌细胞的生长。.
Keywords: Carcinoma, squamous cell; Esophageal neoplasms; Genome-wide association study; Kruppel-like factor 4; Zinc finger protein 750.