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Abstract：
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
摘要：
■SLC25A22，线粒体载体系统（MCS）家族成员，编码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至关重要的作用。胆囊癌（GBC）是最常见的胆道恶性肿瘤，预后不良。我们旨在确定SLC25A22在GBC中的表达和功能。
■进行免疫组织化学（IHC）染色分析和定量实时PCR（qRT-PCR）以确定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测定和集落形成测定评估细胞活力。通过伤口愈合和transwell测定法研究了细胞在体外的迁移和侵袭。通过流式细胞术测量细胞凋亡的膜联蛋白V/PI染色测定。SLC25A22在体内的作用用皮下异种移植物进行。
■我们表明SLC25A22的表达在GBC肿瘤组织和细胞系中显著上调。SLC25A22的下调在体外和体内抑制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和上调切割的PARP促进线粒体凋亡，细胞色素C,BAX介导MAPK/ERK通路。
■我们的研究发现SLC25A22促进了GBC激活MAPK/ERK通路的发展。SLC25A22有潜力作为GBC的癌症诊断和相关治疗的靶点。
■进行免疫组织化学（IHC）染色分析和定量实时PCR（qRT-PCR）以确定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测定和集落形成测定评估细胞活力。通过伤口愈合和transwell测定法研究了细胞在体外的迁移和侵袭。通过流式细胞术测量细胞凋亡的膜联蛋白V/PI染色测定。SLC25A22在体内的作用用皮下异种移植物进行。
■我们表明SLC25A22的表达在GBC肿瘤组织和细胞系中显著上调。SLC25A22的下调在体外和体内抑制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和上调切割的PARP促进线粒体凋亡，细胞色素C,BAX介导MAPK/ERK通路。
■我们的研究发现SLC25A22促进了GBC激活MAPK/ERK通路的发展。SLC25A22有潜力作为GBC的癌症诊断和相关治疗的靶点。
