Abstract
BackgroundSLC25A22, 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.MethodsImmunohistochemistry (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.ResultsWe 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.ConclusionsOur 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.
Highlights
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
Our study identified that SLC25A22 promoted development of Gallbladder cancer (GBC) activating mitogen-activated protein kinase (MAPK)/extracellular regulated protein kinases (ERK) pathway
SLC25A22 has a potential to be used as a target for cancer diagnosis of GBC and related therapies
Summary
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. Gallbladder cancer (GBC) is the most common biliary tract malignancy and the fifth most common gastrointestinal cancer [1]. The 53-member canonical SLC25A transporter groups and several identified noncanonical transporters are involved in the mitochondrial carrier system (MCS) in mammals. This system transports small molecules between the mitochondria and cytoplasm [4]. SLC25A22 as a member of MCS family, was identified to encoded a mitochondrial glutamate transporter [5]. Wong and Li et al revealed that the overexpression of
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