CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability
Abstract Background Circular RNAs (circRNAs) play important roles in cancer development and progression. The purpose of this study is to identify aberrantly expressed circRNAs in gastric cancer (GC), unravel their roles in GC progression, and provide new targets for GC diagnosis and therapy. Methods...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-08-01
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| Series: | Molecular Cancer |
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| Online Access: | https://doi.org/10.1186/s12943-021-01390-y |
| _version_ | 1818903131208024064 |
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| author | Yu Zhang Jiajia Jiang Jiayin Zhang Han Shen Maoye Wang Zhen Guo Xueyan Zang Hui Shi Jiayan Gao Hui Cai Xinjian Fang Hui Qian Wenrong Xu Xu Zhang |
| author_facet | Yu Zhang Jiajia Jiang Jiayin Zhang Han Shen Maoye Wang Zhen Guo Xueyan Zang Hui Shi Jiayan Gao Hui Cai Xinjian Fang Hui Qian Wenrong Xu Xu Zhang |
| author_sort | Yu Zhang |
| collection | DOAJ |
| description | Abstract Background Circular RNAs (circRNAs) play important roles in cancer development and progression. The purpose of this study is to identify aberrantly expressed circRNAs in gastric cancer (GC), unravel their roles in GC progression, and provide new targets for GC diagnosis and therapy. Methods Bioinformatic analyses were performed to identify the aberrantly expression of hsa_circ_0061137 (termed as circDIDO1) in GC. Gain- and loss-of-function studies were performed to examine the biological roles of circDIDO1 in GC progression. Tagged RNA affinity purification, mass spectrometry, immunofluorescence, co-immunoprecipitation, and Western blot were used to identify circRNA-interacting and circRNA-encoded proteins. RNA sequencing, qRT-PCR, and Western blot were performed to analyze circRNA-regulated downstream target genes and signaling pathways. Mouse tumor models were used to analyze the effects of circDIDO1 on GC growth and metastasis. Results CircDIDO1 was transcribed from human DIDO1 (death-inducer obliterator 1) gene and formed by back-splicing of exons 2–6 of the linear transcript. circDIDO1 was down-regulated in GC tissues and its low levels were associated with larger tumor size, distal metastasis, and poor prognosis. CircDIDO1 overexpression inhibited while knockdown promoted GC cell proliferation, migration and invasion. CircDIDO1 overexpression suppressed GC growth and metastasis in mouse tumor models. Mechanistically, circDIDO1 encoded a novel 529aa protein that directly interacted with poly ADP-ribose polymerase 1 (PARP1) and inhibited its activity. CircDIDO1 also specifically bound to peroxiredoxin 2 (PRDX2) and promoted RBX1-mediated ubiquitination and degradation of PRDX2, which led to the inactivation of its downstream signaling pathways. Conclusions CircDIDO1 is a new circRNA that has tumor suppressor function in GC and it may serve as a potential prognostic biomarker and therapeutic target for GC. |
| first_indexed | 2024-12-19T20:46:40Z |
| format | Article |
| id | doaj.art-c6965b2a89ca4a47a816cb0ad5d5e6b6 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-19T20:46:40Z |
| publishDate | 2021-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-c6965b2a89ca4a47a816cb0ad5d5e6b62022-12-21T20:06:14ZengBMCMolecular Cancer1476-45982021-08-0120111710.1186/s12943-021-01390-yCircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stabilityYu Zhang0Jiajia Jiang1Jiayin Zhang2Han Shen3Maoye Wang4Zhen Guo5Xueyan Zang6Hui Shi7Jiayan Gao8Hui Cai9Xinjian Fang10Hui Qian11Wenrong Xu12Xu Zhang13Aoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu UniversityAoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu UniversityAoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu UniversityJiangsu Key Laboratory of Medical Science and Laboratory Medicine, School of Medicine, Jiangsu UniversityAoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu UniversityAoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu UniversityAoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu UniversityAoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu UniversityAoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu UniversityKey Laboratory of Molecular Diagnostics and Precision Medicine for Surgical Oncology in Gansu Province, Gansu Hospital of Jiangsu UniversityDepartment of Oncology, Lianyungang Hospital Affiliated To Jiangsu UniversityAoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu UniversityAoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu UniversityAoyang Cancer Institute, Affiliated Aoyang Hospital of Jiangsu UniversityAbstract Background Circular RNAs (circRNAs) play important roles in cancer development and progression. The purpose of this study is to identify aberrantly expressed circRNAs in gastric cancer (GC), unravel their roles in GC progression, and provide new targets for GC diagnosis and therapy. Methods Bioinformatic analyses were performed to identify the aberrantly expression of hsa_circ_0061137 (termed as circDIDO1) in GC. Gain- and loss-of-function studies were performed to examine the biological roles of circDIDO1 in GC progression. Tagged RNA affinity purification, mass spectrometry, immunofluorescence, co-immunoprecipitation, and Western blot were used to identify circRNA-interacting and circRNA-encoded proteins. RNA sequencing, qRT-PCR, and Western blot were performed to analyze circRNA-regulated downstream target genes and signaling pathways. Mouse tumor models were used to analyze the effects of circDIDO1 on GC growth and metastasis. Results CircDIDO1 was transcribed from human DIDO1 (death-inducer obliterator 1) gene and formed by back-splicing of exons 2–6 of the linear transcript. circDIDO1 was down-regulated in GC tissues and its low levels were associated with larger tumor size, distal metastasis, and poor prognosis. CircDIDO1 overexpression inhibited while knockdown promoted GC cell proliferation, migration and invasion. CircDIDO1 overexpression suppressed GC growth and metastasis in mouse tumor models. Mechanistically, circDIDO1 encoded a novel 529aa protein that directly interacted with poly ADP-ribose polymerase 1 (PARP1) and inhibited its activity. CircDIDO1 also specifically bound to peroxiredoxin 2 (PRDX2) and promoted RBX1-mediated ubiquitination and degradation of PRDX2, which led to the inactivation of its downstream signaling pathways. Conclusions CircDIDO1 is a new circRNA that has tumor suppressor function in GC and it may serve as a potential prognostic biomarker and therapeutic target for GC.https://doi.org/10.1186/s12943-021-01390-yCircRNADIDO1Gastric cancerBiomarkerTarget |
| spellingShingle | Yu Zhang Jiajia Jiang Jiayin Zhang Han Shen Maoye Wang Zhen Guo Xueyan Zang Hui Shi Jiayan Gao Hui Cai Xinjian Fang Hui Qian Wenrong Xu Xu Zhang CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability Molecular Cancer CircRNA DIDO1 Gastric cancer Biomarker Target |
| title | CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability |
| title_full | CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability |
| title_fullStr | CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability |
| title_full_unstemmed | CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability |
| title_short | CircDIDO1 inhibits gastric cancer progression by encoding a novel DIDO1-529aa protein and regulating PRDX2 protein stability |
| title_sort | circdido1 inhibits gastric cancer progression by encoding a novel dido1 529aa protein and regulating prdx2 protein stability |
| topic | CircRNA DIDO1 Gastric cancer Biomarker Target |
| url | https://doi.org/10.1186/s12943-021-01390-y |
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