circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expression
Aberrant expression of circular RNAs (circRNAs) is involved in cancer progression through interaction with RNA-binding proteins (RBPs). Herein, we screened circRNA expression of A549 cells in circBase and the crosslinking immunoprecipitation (CLIP) data of human antigen R (HuR), an extensively studi...
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| Format: | Article |
| Language: | English |
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Elsevier
2021-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253120303681 |
| _version_ | 1818948101871763456 |
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| author | Yingkuan Liang Hui Wang Bing Chen Qixing Mao Wenjie Xia Te Zhang Xuming Song Zeyu Zhang Lin Xu Gaochao Dong Feng Jiang |
| author_facet | Yingkuan Liang Hui Wang Bing Chen Qixing Mao Wenjie Xia Te Zhang Xuming Song Zeyu Zhang Lin Xu Gaochao Dong Feng Jiang |
| author_sort | Yingkuan Liang |
| collection | DOAJ |
| description | Aberrant expression of circular RNAs (circRNAs) is involved in cancer progression through interaction with RNA-binding proteins (RBPs). Herein, we screened circRNA expression of A549 cells in circBase and the crosslinking immunoprecipitation (CLIP) data of human antigen R (HuR), an extensively studied RBP, and identified a circRNA, circ-defective in cullin neddylation 1 domain containing 4 (circDCUN1D4), originating from the DCUN1D4 gene transcript. circDCUN1D4 is downregulated in tumor samples under the mediation of DExH-box helicase 9 (DHX9), which inhibits the formation of circRNA by binding inverted repeat Alus (IRAlus) in flanking sequences. circDCUN1D4 depletion promoted invasion in vitro and metastasis in vivo. Importantly, the interaction between circDCUN1D4 and HuR increased the transportation of HuR to the cytoplasm. circDCUN1D4 acts as a scaffold to facilitate the interaction between the HuR protein and thioredoxin-interacting protein (TXNIP) mRNA, which enhances the stability of the TXNIP mRNA. Additionally, circDCUN1D4 directly interacts with TXNIP mRNA through base complementation, indicating the formation of the circDCUN1D4/HuR/TXNIP RNA-protein ternary complex. Furthermore, circDCUN1D4 suppressed metastasis and glycolysis of lung cancer cells in a TXNIP-dependent manner. Clinically, the downregulated expression of circDCUN1D4 was more prevalent in lymph node metastatic tissues and served as an independent risk factor for the overall survival of lung adenocarcinoma (LUAD) patients. These findings demonstrated that a novel circRNA, circDCUN1D4, is involved in the metastasis and glycolysis of LUAD. |
| first_indexed | 2024-12-20T08:41:27Z |
| format | Article |
| id | doaj.art-6e8cb205df094802a73cb782dadf2a08 |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-20T08:41:27Z |
| publishDate | 2021-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-6e8cb205df094802a73cb782dadf2a082022-12-21T19:46:23ZengElsevierMolecular Therapy: Nucleic Acids2162-25312021-03-0123355368circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expressionYingkuan Liang0Hui Wang1Bing Chen2Qixing Mao3Wenjie Xia4Te Zhang5Xuming Song6Zeyu Zhang7Lin Xu8Gaochao Dong9Feng Jiang10The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, PR China; Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing 210029, PR China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, PR China; Department of Thoracic Surgery, The First Affiliated Hospital of Suchow University, Suzhou, PR ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, PR China; Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing 210029, PR China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, PR ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, PR China; Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing 210029, PR China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, PR ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, PR China; Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing 210029, PR China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, PR ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, PR China; Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing 210029, PR China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, PR ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, PR China; Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing 210029, PR China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, PR ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, PR China; Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing 210029, PR China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, PR ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, PR China; Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing 210029, PR China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, PR ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, PR China; Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing 210029, PR China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, PR ChinaThe Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, PR China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, PR China; Corresponding author: Gaochao Dong, The Affiliated Cancer Hospital of Nanjing Medical University, Baiziting 42, Nanjing 210009, PR China.The Affiliated Cancer Hospital of Nanjing Medical University, Nanjing, PR China; Department of Thoracic Surgery, Jiangsu Cancer Hospital, Jiangsu Institute of Cancer Research, Nanjing 210029, PR China; Jiangsu Key Laboratory of Molecular and Translational Cancer Research, Cancer Institute of Jiangsu Province, Nanjing, PR China; Corresponding author: Feng Jiang, The Affiliated Cancer Hospital of Nanjing Medical University, Baiziting 42, Nanjing 210009, PR China.Aberrant expression of circular RNAs (circRNAs) is involved in cancer progression through interaction with RNA-binding proteins (RBPs). Herein, we screened circRNA expression of A549 cells in circBase and the crosslinking immunoprecipitation (CLIP) data of human antigen R (HuR), an extensively studied RBP, and identified a circRNA, circ-defective in cullin neddylation 1 domain containing 4 (circDCUN1D4), originating from the DCUN1D4 gene transcript. circDCUN1D4 is downregulated in tumor samples under the mediation of DExH-box helicase 9 (DHX9), which inhibits the formation of circRNA by binding inverted repeat Alus (IRAlus) in flanking sequences. circDCUN1D4 depletion promoted invasion in vitro and metastasis in vivo. Importantly, the interaction between circDCUN1D4 and HuR increased the transportation of HuR to the cytoplasm. circDCUN1D4 acts as a scaffold to facilitate the interaction between the HuR protein and thioredoxin-interacting protein (TXNIP) mRNA, which enhances the stability of the TXNIP mRNA. Additionally, circDCUN1D4 directly interacts with TXNIP mRNA through base complementation, indicating the formation of the circDCUN1D4/HuR/TXNIP RNA-protein ternary complex. Furthermore, circDCUN1D4 suppressed metastasis and glycolysis of lung cancer cells in a TXNIP-dependent manner. Clinically, the downregulated expression of circDCUN1D4 was more prevalent in lymph node metastatic tissues and served as an independent risk factor for the overall survival of lung adenocarcinoma (LUAD) patients. These findings demonstrated that a novel circRNA, circDCUN1D4, is involved in the metastasis and glycolysis of LUAD.http://www.sciencedirect.com/science/article/pii/S2162253120303681circDCUN1D4TXNIPglycolysisLUADHuRcircular RNA |
| spellingShingle | Yingkuan Liang Hui Wang Bing Chen Qixing Mao Wenjie Xia Te Zhang Xuming Song Zeyu Zhang Lin Xu Gaochao Dong Feng Jiang circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expression Molecular Therapy: Nucleic Acids circDCUN1D4 TXNIP glycolysis LUAD HuR circular RNA |
| title | circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expression |
| title_full | circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expression |
| title_fullStr | circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expression |
| title_full_unstemmed | circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expression |
| title_short | circDCUN1D4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing TXNIP expression |
| title_sort | circdcun1d4 suppresses tumor metastasis and glycolysis in lung adenocarcinoma by stabilizing txnip expression |
| topic | circDCUN1D4 TXNIP glycolysis LUAD HuR circular RNA |
| url | http://www.sciencedirect.com/science/article/pii/S2162253120303681 |
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