Du Pengcheng, Liang Haibin, Fu Xiaowei, Wu Peng, Wang Chao, Chen Haimin, Zheng Bingbing, Zhang Jun, Hu Shuanghui, Zeng Rengui, Liang Bo, Fang Lu
1Department of General Surgery, Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Nanchang, 330006 China.
Jiangxi Province Key Laboratory of Molecular Medicine, No. 1 Minde Road, Nanchang, 330006 China.
Cancer Cell Int. 2019 Feb 14;19:33. doi: 10.1186/s12935-019-0746-9. eCollection 2019.
SLC25A22, a member of mitochondrial carrier system (MCS) family encoding a mitochondrial glutamate transporter, has been reported to have vital roles in promoting proliferation and migration in cancer. Gallbladder cancer (GBC) is the most common biliary tract malignancy and has a poor prognosis. We aimed to determine the expression and function of SLC25A22 in GBC.
Immunohistochemistry (IHC) staining analysis and quantitative real-time PCR (qRT-PCR) were conducted to determine the expression of SLC25A22 in GBC tissues. Human NOZ and GBC-SD cells were used to perform the experiments. The protein expression was detected by western-blot analysis. Cell viability was evaluated via CCK-8 assay and colony formation assay. Cell migration and invasion in vitro were investigated by wound healing and transwell assay. Annexin V/PI staining assay for apoptosis were measured by flow cytometry. The effect of SLC25A22 in vivo was conducted with subcutaneous xenograft.
We indicated that the expression of SLC25A22 was significantly upregulated in GBC tumor tissues as well as cell lines. Downregulation of SLC25A22 inhibited GBC cell growth and proliferation in vitro and in vivo and also had an effect on metastasis of GBC cells through the EMT processes. In addition, inhibition of SLC25A22 promoted mitochondrial apoptosis via downregulating BCL-2 and upregulating cleaved PARP, Cytochrome-c, and BAX mediated by MAPK/ERK pathway.
Our study identified that SLC25A22 promoted development of GBC activating MAPK/ERK pathway. SLC25A22 has a potential to be used as a target for cancer diagnosis of GBC and related therapies.
SLC25A22是线粒体载体系统（MCS）家族的成员，编码一种线粒体谷氨酸转运体，据报道在促进癌症的增殖和迁移中起着重要作用。胆囊癌（GBC）是最常见的胆道恶性肿瘤，预后较差。我们旨在确定SLC25A22在GBC中的表达和功能。
采用免疫组织化学（IHC）染色分析和定量实时PCR（qRT-PCR）来确定SLC25A22在GBC组织中的表达。使用人NOZ和GBC-SD细胞进行实验。通过蛋白质印迹分析检测蛋白质表达。通过CCK-8测定法和集落形成测定法评估细胞活力。通过伤口愈合和Transwell测定法研究体外细胞迁移和侵袭。通过流式细胞术测量Annexin V/PI染色法检测细胞凋亡。通过皮下异种移植研究SLC25A22在体内的作用。
我们表明，SLC25A22在GBC肿瘤组织以及细胞系中的表达显著上调。SLC25A22的下调在体外和体内均抑制GBC细胞的生长和增殖，并且还通过EMT过程对GBC细胞的转移产生影响。此外，抑制SLC25A22通过下调BCL-2并上调由MAPK/ERK途径介导的裂解的PARP、细胞色素c和BAX来促进线粒体凋亡。
我们的研究发现SLC25A22通过激活MAPK/ERK途径促进GBC的发展。SLC25A22有潜力用作GBC癌症诊断和相关治疗的靶点。
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