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SLC25A22 promotes proliferation and metastasis by activating MAPK/ERK pathway in gallbladder cancer

BACKGROUND: 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 pr...

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Autores principales: Du, Pengcheng, Liang, Haibin, Fu, Xiaowei, Wu, Peng, Wang, Chao, Chen, Haimin, Zheng, Bingbing, Zhang, Jun, Hu, Shuanghui, Zeng, Rengui, Liang, Bo, Fang, Lu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376740/
https://www.ncbi.nlm.nih.gov/pubmed/30814911
http://dx.doi.org/10.1186/s12935-019-0746-9
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author Du, Pengcheng
Liang, Haibin
Fu, Xiaowei
Wu, Peng
Wang, Chao
Chen, Haimin
Zheng, Bingbing
Zhang, Jun
Hu, Shuanghui
Zeng, Rengui
Liang, Bo
Fang, Lu
author_facet Du, Pengcheng
Liang, Haibin
Fu, Xiaowei
Wu, Peng
Wang, Chao
Chen, Haimin
Zheng, Bingbing
Zhang, Jun
Hu, Shuanghui
Zeng, Rengui
Liang, Bo
Fang, Lu
author_sort Du, Pengcheng
collection PubMed
description BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
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spelling pubmed-63767402019-02-27 SLC25A22 promotes proliferation and metastasis by activating MAPK/ERK pathway in gallbladder cancer Du, Pengcheng Liang, Haibin Fu, Xiaowei Wu, Peng Wang, Chao Chen, Haimin Zheng, Bingbing Zhang, Jun Hu, Shuanghui Zeng, Rengui Liang, Bo Fang, Lu Cancer Cell Int Primary Research BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. BioMed Central 2019-02-14 /pmc/articles/PMC6376740/ /pubmed/30814911 http://dx.doi.org/10.1186/s12935-019-0746-9 Text en © The Author(s) 2019 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Primary Research
Du, Pengcheng
Liang, Haibin
Fu, Xiaowei
Wu, Peng
Wang, Chao
Chen, Haimin
Zheng, Bingbing
Zhang, Jun
Hu, Shuanghui
Zeng, Rengui
Liang, Bo
Fang, Lu
SLC25A22 promotes proliferation and metastasis by activating MAPK/ERK pathway in gallbladder cancer
title SLC25A22 promotes proliferation and metastasis by activating MAPK/ERK pathway in gallbladder cancer
title_full SLC25A22 promotes proliferation and metastasis by activating MAPK/ERK pathway in gallbladder cancer
title_fullStr SLC25A22 promotes proliferation and metastasis by activating MAPK/ERK pathway in gallbladder cancer
title_full_unstemmed SLC25A22 promotes proliferation and metastasis by activating MAPK/ERK pathway in gallbladder cancer
title_short SLC25A22 promotes proliferation and metastasis by activating MAPK/ERK pathway in gallbladder cancer
title_sort slc25a22 promotes proliferation and metastasis by activating mapk/erk pathway in gallbladder cancer
topic Primary Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6376740/
https://www.ncbi.nlm.nih.gov/pubmed/30814911
http://dx.doi.org/10.1186/s12935-019-0746-9
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