Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, P.R. China.
Oncol Rep. 2017 Oct;38(4):2229-2236. doi: 10.3892/or.2017.5868. Epub 2017 Aug 1.
Zinc finger protein 307 (ZNF307) is a new Krüppel-associated box zinc-finger protein gene and a member of the zinc-finger family of transcriptional factors. Notably, the role of ZNF307 and its underlying mechanisms involved in hepatocarcinogenesis are poorly investigated. In the present study, we found that the expression of ZNF307 was significantly downregulated in hepatocellular carcinoma (HCC) tissues, compared with that in adjacent non-tumor tissues. In vitro studies further demonstrated that ectopic expression of ZNF307 in HCC cell lines Bel7402 and HCCLM3 significantly reduced cell proliferation, migration and invasive ability. Concordantly, knockdown of ZNF307 increased cell proliferation, migration and invasive ability of HCC cell lines MHCC97L and QGY7701. In vivo functional studies showed that upregulation of ZNF307 expression in Bel7402 cells led to a suppression of tumorigenicity in mice, while knockdown of ZNF307 in MHCC97L cells resulted in reverse. effects. Importantly, flow cytometric analysis showed that ZNF307 overexpression increased the incidence of apoptosis, while ZNF307 knockdown decreased the incidence of apoptosis. Consistently, key regulators in apoptosis, such as caspase-3, BAX and BCL-2 were also regulated by ZNF307. Therefore, our results indicate that ZNF307 may serve as a tumor suppressor and inhibits cell proliferation of HCC via inducing apoptosis.
锌指蛋白 307(ZNF307)是一种新的 Krüppel 相关盒锌指蛋白基因,是转录因子锌指家族的成员。值得注意的是,ZNF307 的作用及其在肝癌发生中的潜在机制尚未得到充分研究。本研究发现,与相邻非肿瘤组织相比,ZNF307 在肝癌组织中的表达明显下调。体外研究进一步表明,在肝癌细胞系 Bel7402 和 HCCLM3 中外源表达 ZNF307 显著降低了细胞的增殖、迁移和侵袭能力。相应地,敲低 ZNF307 增加了肝癌细胞系 MHCC97L 和 QGY7701 的增殖、迁移和侵袭能力。体内功能研究表明,上调 Bel7402 细胞中 ZNF307 的表达导致小鼠肿瘤发生受到抑制,而敲低 MHCC97L 细胞中的 ZNF307 则产生相反的效果。重要的是,流式细胞术分析表明,ZNF307 过表达增加了细胞凋亡的发生率,而 ZNF307 敲低则降低了细胞凋亡的发生率。同样,凋亡的关键调节因子,如 caspase-3、BAX 和 BCL-2 也受到 ZNF307 的调节。因此,我们的结果表明,ZNF307 可能作为一种肿瘤抑制因子,通过诱导细胞凋亡抑制肝癌细胞的增殖。