Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulation
Objective: Protein disulfide isomerase A3 (PDIA3) promotes the correct folding of newly synthesized glycoproteins in the endoplasmic reticulum. PDIA3 is overexpressed in most tumors, and it may become a biomarker of cancer prognosis and immunotherapy. Our study aims to detect the expression level of...
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| Language: | English |
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Elsevier
2024-04-01
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| Series: | Biomedicine & Pharmacotherapy |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0753332224002208 |
| _version_ | 1797248450417393664 |
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| author | Min Yang Qianxiu Li Huan Yang Yifan Li Lan Lu Xu Wu Yubin Liu Wanping Li Jing Shen Zhangang Xiao Yueshui Zhao Fukuan Du Yu Chen Shuai Deng Chi Hin Cho Xiaobing Li Mingxing Li |
| author_facet | Min Yang Qianxiu Li Huan Yang Yifan Li Lan Lu Xu Wu Yubin Liu Wanping Li Jing Shen Zhangang Xiao Yueshui Zhao Fukuan Du Yu Chen Shuai Deng Chi Hin Cho Xiaobing Li Mingxing Li |
| author_sort | Min Yang |
| collection | DOAJ |
| description | Objective: Protein disulfide isomerase A3 (PDIA3) promotes the correct folding of newly synthesized glycoproteins in the endoplasmic reticulum. PDIA3 is overexpressed in most tumors, and it may become a biomarker of cancer prognosis and immunotherapy. Our study aims to detect the expression level of PDIA3 in gastric cancer (GC) and its association with GC development as wells as the underlying mechanisms. Methods: GC cell lines with PDIA3 knockdown by siRNA, CRISPR-cas9 sgRNAs or a pharmacological inhibitor of LOC14 were prepared and used. PDIA3 knockout GC cells were established by CRISPR-cas9-PDIA3 system. The proliferation, migration, invasion and cell cycle of GC cells were analyzed by cell counting kit-8 assay, wound healing assay, transwell assay and flow cytometry, respectively. Immunodeficient nude mice was used to evaluate the role of PDIA3 in tumor formation. Quantitative PCR and western blot were used for examining gene and protein expressions. RNA sequencing was performed to see the altered gene expression. Results: The expressions of PDIA3 in GC tissues and cells were increased significantly, and its expression was negatively correlated with the three-year survival rate of GC patients. Down-regulation of PDIA3 by siRNA, LOC14 or CRISPR-cas9 significantly inhibited proliferation, invasion and migration of GC cells TMK1 and AGS, with cell cycle arrested at G2/M phase. Meanwhile, decreased PDIA3 significantly inhibited growth of tumor xenograft in vivo. It was found that cyclin G1 (encoded by CCNG1 gene) expression was decreased by downregulation of PDIA3 in GC cells both in vitro and in vivo. In addition, protein levels of other cell cycle related factors including cyclin D1, CDK2, and CDK6 were also significantly decreased. Further study showed that STAT3 was associated with PDIA3-mediated cyclin G1 regulation. Conclusion: PDIA3 plays an oncogenic role in GC. Our findings unfolded the functional role of PDIA3 in GC development and highlighted a novel target for cancer therapeutic strategy. |
| first_indexed | 2024-03-07T21:29:17Z |
| format | Article |
| id | doaj.art-f473c836effb4376a195eca9f80c9f86 |
| institution | Directory Open Access Journal |
| issn | 0753-3322 |
| language | English |
| last_indexed | 2024-04-24T20:14:47Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
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| series | Biomedicine & Pharmacotherapy |
| spelling | doaj.art-f473c836effb4376a195eca9f80c9f862024-03-23T06:22:47ZengElsevierBiomedicine & Pharmacotherapy0753-33222024-04-01173116336Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulationMin Yang0Qianxiu Li1Huan Yang2Yifan Li3Lan Lu4Xu Wu5Yubin Liu6Wanping Li7Jing Shen8Zhangang Xiao9Yueshui Zhao10Fukuan Du11Yu Chen12Shuai Deng13Chi Hin Cho14Xiaobing Li15Mingxing Li16Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Nanbu people's Hospital, Ministry of Pharmacy, Nanchong, Sichuan, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, ChinaAntibiotics Research and Re-evaluation Key Laboratory of Sichuan Province, Sichuan Industrial Institute of Antibiotics, School of Pharmacy, Chengdu University, Chengdu, Sichuan, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, ChinaLaboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China; Correspondence to: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646100, China.Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, China; Cell Therapy & Cell Drugs of Luzhou Key Laboratory, Luzhou, Sichuan, China; South Sichuan Institute of Translational Medicine, Luzhou, Sichuan, China; Correspondence to: Laboratory of Molecular Pharmacology, Department of Pharmacology, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan 646100, China.Objective: Protein disulfide isomerase A3 (PDIA3) promotes the correct folding of newly synthesized glycoproteins in the endoplasmic reticulum. PDIA3 is overexpressed in most tumors, and it may become a biomarker of cancer prognosis and immunotherapy. Our study aims to detect the expression level of PDIA3 in gastric cancer (GC) and its association with GC development as wells as the underlying mechanisms. Methods: GC cell lines with PDIA3 knockdown by siRNA, CRISPR-cas9 sgRNAs or a pharmacological inhibitor of LOC14 were prepared and used. PDIA3 knockout GC cells were established by CRISPR-cas9-PDIA3 system. The proliferation, migration, invasion and cell cycle of GC cells were analyzed by cell counting kit-8 assay, wound healing assay, transwell assay and flow cytometry, respectively. Immunodeficient nude mice was used to evaluate the role of PDIA3 in tumor formation. Quantitative PCR and western blot were used for examining gene and protein expressions. RNA sequencing was performed to see the altered gene expression. Results: The expressions of PDIA3 in GC tissues and cells were increased significantly, and its expression was negatively correlated with the three-year survival rate of GC patients. Down-regulation of PDIA3 by siRNA, LOC14 or CRISPR-cas9 significantly inhibited proliferation, invasion and migration of GC cells TMK1 and AGS, with cell cycle arrested at G2/M phase. Meanwhile, decreased PDIA3 significantly inhibited growth of tumor xenograft in vivo. It was found that cyclin G1 (encoded by CCNG1 gene) expression was decreased by downregulation of PDIA3 in GC cells both in vitro and in vivo. In addition, protein levels of other cell cycle related factors including cyclin D1, CDK2, and CDK6 were also significantly decreased. Further study showed that STAT3 was associated with PDIA3-mediated cyclin G1 regulation. Conclusion: PDIA3 plays an oncogenic role in GC. Our findings unfolded the functional role of PDIA3 in GC development and highlighted a novel target for cancer therapeutic strategy.http://www.sciencedirect.com/science/article/pii/S0753332224002208PDIA3Gastric cancerCCNG1CRISPR-Cas9STAT3 |
| spellingShingle | Min Yang Qianxiu Li Huan Yang Yifan Li Lan Lu Xu Wu Yubin Liu Wanping Li Jing Shen Zhangang Xiao Yueshui Zhao Fukuan Du Yu Chen Shuai Deng Chi Hin Cho Xiaobing Li Mingxing Li Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulation Biomedicine & Pharmacotherapy PDIA3 Gastric cancer CCNG1 CRISPR-Cas9 STAT3 |
| title | Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulation |
| title_full | Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulation |
| title_fullStr | Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulation |
| title_full_unstemmed | Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulation |
| title_short | Downregulation of PDIA3 inhibits gastric cancer cell growth through cell cycle regulation |
| title_sort | downregulation of pdia3 inhibits gastric cancer cell growth through cell cycle regulation |
| topic | PDIA3 Gastric cancer CCNG1 CRISPR-Cas9 STAT3 |
| url | http://www.sciencedirect.com/science/article/pii/S0753332224002208 |
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