ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC
Lung adenocarcinoma (LUAD) is the main histological type of lung cancer, which is the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) were recently revealed to be involved in various cancers. However, the clinical relevance and potential biological roles of most lncRNAs in LUA...
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| Format: | Article |
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Frontiers Media S.A.
2021-03-01
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| Series: | Frontiers in Cell and Developmental Biology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fcell.2021.631259/full |
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| author | Ruimin Chang Ruimin Chang Ruimin Chang Ruimin Chang Xiaoxiong Xiao Xiaoxiong Xiao Xiaoxiong Xiao Yao Fu Yao Fu Yao Fu Chunfang Zhang Chunfang Zhang Chunfang Zhang Xiaoyan Zhu Yang Gao Yang Gao Yang Gao |
| author_facet | Ruimin Chang Ruimin Chang Ruimin Chang Ruimin Chang Xiaoxiong Xiao Xiaoxiong Xiao Xiaoxiong Xiao Yao Fu Yao Fu Yao Fu Chunfang Zhang Chunfang Zhang Chunfang Zhang Xiaoyan Zhu Yang Gao Yang Gao Yang Gao |
| author_sort | Ruimin Chang |
| collection | DOAJ |
| description | Lung adenocarcinoma (LUAD) is the main histological type of lung cancer, which is the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) were recently revealed to be involved in various cancers. However, the clinical relevance and potential biological roles of most lncRNAs in LUAD remain unclear. Here, we identified a prognosis-related lncRNA ITGB1-DT in LUAD. ITGB1-DT was upregulated in LUAD and high expression of ITGB1-DT was correlated with advanced clinical stages and poor overall survival and disease-free survival. Enhanced expression of ITGB1-DT facilitated LUAD cellular proliferation, migration, and invasion, and also lung metastasis in vivo. Knockdown of ITGB1-DT repressed LUAD cellular proliferation, migration, and invasion. ITGB1-DT interacted with EZH2, repressed the binding of EZH2 to ITGB1 promoter, reduced H3K27me3 levels at ITGB1 promoter region, and therefore activated ITGB1 expression. Through upregulating ITGB1, ITGB1-DT activated Wnt/β-catenin pathway and its downstream target MYC in LUAD. The expressions of ITGB1-DT, ITGB1, and MYC were positively correlated with each other in LUAD tissues. Intriguingly, ITGB1-DT was found as a transcriptional target of MYC. MYC directly transcriptionally activated ITGB1-DT expression. Thus, ITGB1-DT formed a positive feedback loop with ITGB1/Wnt/β-catenin/MYC. The oncogenic roles of ITGB1-DT were reversed by depletion of ITGB1 or inhibition of Wnt/β-catenin pathway. In summary, these findings revealed ITGB1-DT as a prognosis-related and oncogenic lncRNA in LUAD via activating the ITGB1-DT/ITGB1/Wnt/β-catenin/MYC positive feedback loop. These results implicated ITGB1-DT as a potential prognostic biomarker and therapeutic target for LUAD. |
| first_indexed | 2024-12-23T23:32:31Z |
| format | Article |
| id | doaj.art-b66cb88bec9742b19c3ffe7f180ebc7a |
| institution | Directory Open Access Journal |
| issn | 2296-634X |
| language | English |
| last_indexed | 2024-12-23T23:32:31Z |
| publishDate | 2021-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Cell and Developmental Biology |
| spelling | doaj.art-b66cb88bec9742b19c3ffe7f180ebc7a2022-12-21T17:25:59ZengFrontiers Media S.A.Frontiers in Cell and Developmental Biology2296-634X2021-03-01910.3389/fcell.2021.631259631259ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYCRuimin Chang0Ruimin Chang1Ruimin Chang2Ruimin Chang3Xiaoxiong Xiao4Xiaoxiong Xiao5Xiaoxiong Xiao6Yao Fu7Yao Fu8Yao Fu9Chunfang Zhang10Chunfang Zhang11Chunfang Zhang12Xiaoyan Zhu13Yang Gao14Yang Gao15Yang Gao16Department of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, ChinaHunan Engineering Research Center for Pulmonary Nodules Precise Diagnosis & Treatment, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaHunan Key Laboratory of Skin Cancer and Psoriasis, Changsha, ChinaDepartment of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, ChinaHunan Engineering Research Center for Pulmonary Nodules Precise Diagnosis & Treatment, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaDepartment of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, ChinaHunan Engineering Research Center for Pulmonary Nodules Precise Diagnosis & Treatment, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaDepartment of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, ChinaHunan Engineering Research Center for Pulmonary Nodules Precise Diagnosis & Treatment, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaDepartment of Anesthesiology, Xiangya Hospital, Central South University, Changsha, ChinaDepartment of Thoracic Surgery, Xiangya Hospital, Central South University, Changsha, ChinaHunan Engineering Research Center for Pulmonary Nodules Precise Diagnosis & Treatment, Changsha, ChinaNational Clinical Research Center for Geriatric Disorders, Changsha, ChinaLung adenocarcinoma (LUAD) is the main histological type of lung cancer, which is the leading cause of cancer-related deaths. Long non-coding RNAs (lncRNAs) were recently revealed to be involved in various cancers. However, the clinical relevance and potential biological roles of most lncRNAs in LUAD remain unclear. Here, we identified a prognosis-related lncRNA ITGB1-DT in LUAD. ITGB1-DT was upregulated in LUAD and high expression of ITGB1-DT was correlated with advanced clinical stages and poor overall survival and disease-free survival. Enhanced expression of ITGB1-DT facilitated LUAD cellular proliferation, migration, and invasion, and also lung metastasis in vivo. Knockdown of ITGB1-DT repressed LUAD cellular proliferation, migration, and invasion. ITGB1-DT interacted with EZH2, repressed the binding of EZH2 to ITGB1 promoter, reduced H3K27me3 levels at ITGB1 promoter region, and therefore activated ITGB1 expression. Through upregulating ITGB1, ITGB1-DT activated Wnt/β-catenin pathway and its downstream target MYC in LUAD. The expressions of ITGB1-DT, ITGB1, and MYC were positively correlated with each other in LUAD tissues. Intriguingly, ITGB1-DT was found as a transcriptional target of MYC. MYC directly transcriptionally activated ITGB1-DT expression. Thus, ITGB1-DT formed a positive feedback loop with ITGB1/Wnt/β-catenin/MYC. The oncogenic roles of ITGB1-DT were reversed by depletion of ITGB1 or inhibition of Wnt/β-catenin pathway. In summary, these findings revealed ITGB1-DT as a prognosis-related and oncogenic lncRNA in LUAD via activating the ITGB1-DT/ITGB1/Wnt/β-catenin/MYC positive feedback loop. These results implicated ITGB1-DT as a potential prognostic biomarker and therapeutic target for LUAD.https://www.frontiersin.org/articles/10.3389/fcell.2021.631259/fullITGB1-DTlung adenocarcinomaprogressionfeedback loopintegrin β1Wnt/β-catenin pathway |
| spellingShingle | Ruimin Chang Ruimin Chang Ruimin Chang Ruimin Chang Xiaoxiong Xiao Xiaoxiong Xiao Xiaoxiong Xiao Yao Fu Yao Fu Yao Fu Chunfang Zhang Chunfang Zhang Chunfang Zhang Xiaoyan Zhu Yang Gao Yang Gao Yang Gao ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC Frontiers in Cell and Developmental Biology ITGB1-DT lung adenocarcinoma progression feedback loop integrin β1 Wnt/β-catenin pathway |
| title | ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC |
| title_full | ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC |
| title_fullStr | ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC |
| title_full_unstemmed | ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC |
| title_short | ITGB1-DT Facilitates Lung Adenocarcinoma Progression via Forming a Positive Feedback Loop With ITGB1/Wnt/β-Catenin/MYC |
| title_sort | itgb1 dt facilitates lung adenocarcinoma progression via forming a positive feedback loop with itgb1 wnt β catenin myc |
| topic | ITGB1-DT lung adenocarcinoma progression feedback loop integrin β1 Wnt/β-catenin pathway |
| url | https://www.frontiersin.org/articles/10.3389/fcell.2021.631259/full |
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