Long noncoding RNA LUCAT1 enhances the survival and therapeutic effects of mesenchymal stromal cells post-myocardial infarction
Mesenchymal stromal cell (MSC) transplantation has been a promising therapeutic strategy for repairing heart tissues post-myocardial infarction (MI). Nevertheless, its therapeutic efficacy remains low, which is mainly ascribed to the low viability of transplanted MSCs. Recently, long noncoding RNAs...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2022-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2162253121003097 |
| _version_ | 1818919720177369088 |
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| author | Yue Tao Qingnian Liu Rongrong Wu Changchen Xiao Cheng Ni Kan Wang Wangxing Hu Zhiwei Zhong Jing Zhao Qingju Li Dan Zhu Shuhan Zhong Hong Yu Wei Zhu Jinghai Chen Xinyang Hu Jian'an Wang |
| author_facet | Yue Tao Qingnian Liu Rongrong Wu Changchen Xiao Cheng Ni Kan Wang Wangxing Hu Zhiwei Zhong Jing Zhao Qingju Li Dan Zhu Shuhan Zhong Hong Yu Wei Zhu Jinghai Chen Xinyang Hu Jian'an Wang |
| author_sort | Yue Tao |
| collection | DOAJ |
| description | Mesenchymal stromal cell (MSC) transplantation has been a promising therapeutic strategy for repairing heart tissues post-myocardial infarction (MI). Nevertheless, its therapeutic efficacy remains low, which is mainly ascribed to the low viability of transplanted MSCs. Recently, long noncoding RNAs (lncRNAs) have been reported to participate in diverse physiological and pathological processes, but little is known about their role in MSC survival. Using unbiased transcriptome profiling of hypoxia-preconditioned MSCs (HP-MSCs) and normoxic MSCs (N-MSCs), we identified a lncRNA named lung cancer-associated transcript 1 (LUCAT1) under hypoxia. LUCAT1 knockdown reduced the survival of engrafted MSCs and decreased the MSC-based therapeutic potency, as shown by impaired cardiac function, reduced cardiomyocyte survival, and increased fibrosis post-MI. Conversely, LUCAT1 overexpression had the opposite results. Mechanistically, LUCAT1 bound with and recruited jumonji domain-containing 6 (JMJD6) to the promoter of forkhead box Q1 (FOXQ1), which demethylated FOXQ1 at H4R3me2(s) and H3R2me2(a), thus downregulating Bax expression and upregulating Bcl-2 expression to attenuate MSC apoptosis. Therefore, our findings revealed the protective effects of LUCAT1 on MSC apoptosis and demonstrated that the LUCAT1-mediated JMJD6-FOXQ1 pathway might represent a novel target to potentiate the therapeutic effect of MSC-based therapy for ischemic cardiovascular diseases. |
| first_indexed | 2024-12-20T01:10:20Z |
| format | Article |
| id | doaj.art-64078e88d9154cc0853009f1a15e451d |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-20T01:10:20Z |
| publishDate | 2022-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-64078e88d9154cc0853009f1a15e451d2022-12-21T19:58:42ZengElsevierMolecular Therapy: Nucleic Acids2162-25312022-03-0127412426Long noncoding RNA LUCAT1 enhances the survival and therapeutic effects of mesenchymal stromal cells post-myocardial infarctionYue Tao0Qingnian Liu1Rongrong Wu2Changchen Xiao3Cheng Ni4Kan Wang5Wangxing Hu6Zhiwei Zhong7Jing Zhao8Qingju Li9Dan Zhu10Shuhan Zhong11Hong Yu12Wei Zhu13Jinghai Chen14Xinyang Hu15Jian'an Wang16Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China; Institute of Translational Medicine, Zhejiang University, Hangzhou, PR ChinaDepartment of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China; Corresponding author: Xinyang Hu, PhD, Department of Cardiology, The Second Affiliated Hospital, College of Medicine Zhejiang University, Hangzhou 310009, P.R. China.Department of Cardiology, The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, PR China; Cardiovascular Key Laboratory of Zhejiang Province, Hangzhou, PR China; Corresponding author: Jian’an Wang, MD, Department of Cardiology, The Second Affiliated Hospital, College of Medicine Zhejiang University, Hangzhou 310009, P.R. China.Mesenchymal stromal cell (MSC) transplantation has been a promising therapeutic strategy for repairing heart tissues post-myocardial infarction (MI). Nevertheless, its therapeutic efficacy remains low, which is mainly ascribed to the low viability of transplanted MSCs. Recently, long noncoding RNAs (lncRNAs) have been reported to participate in diverse physiological and pathological processes, but little is known about their role in MSC survival. Using unbiased transcriptome profiling of hypoxia-preconditioned MSCs (HP-MSCs) and normoxic MSCs (N-MSCs), we identified a lncRNA named lung cancer-associated transcript 1 (LUCAT1) under hypoxia. LUCAT1 knockdown reduced the survival of engrafted MSCs and decreased the MSC-based therapeutic potency, as shown by impaired cardiac function, reduced cardiomyocyte survival, and increased fibrosis post-MI. Conversely, LUCAT1 overexpression had the opposite results. Mechanistically, LUCAT1 bound with and recruited jumonji domain-containing 6 (JMJD6) to the promoter of forkhead box Q1 (FOXQ1), which demethylated FOXQ1 at H4R3me2(s) and H3R2me2(a), thus downregulating Bax expression and upregulating Bcl-2 expression to attenuate MSC apoptosis. Therefore, our findings revealed the protective effects of LUCAT1 on MSC apoptosis and demonstrated that the LUCAT1-mediated JMJD6-FOXQ1 pathway might represent a novel target to potentiate the therapeutic effect of MSC-based therapy for ischemic cardiovascular diseases.http://www.sciencedirect.com/science/article/pii/S2162253121003097apoptosisMSClncRNAmyocardial infarctionJMJD6FOXQ1 |
| spellingShingle | Yue Tao Qingnian Liu Rongrong Wu Changchen Xiao Cheng Ni Kan Wang Wangxing Hu Zhiwei Zhong Jing Zhao Qingju Li Dan Zhu Shuhan Zhong Hong Yu Wei Zhu Jinghai Chen Xinyang Hu Jian'an Wang Long noncoding RNA LUCAT1 enhances the survival and therapeutic effects of mesenchymal stromal cells post-myocardial infarction Molecular Therapy: Nucleic Acids apoptosis MSC lncRNA myocardial infarction JMJD6 FOXQ1 |
| title | Long noncoding RNA LUCAT1 enhances the survival and therapeutic effects of mesenchymal stromal cells post-myocardial infarction |
| title_full | Long noncoding RNA LUCAT1 enhances the survival and therapeutic effects of mesenchymal stromal cells post-myocardial infarction |
| title_fullStr | Long noncoding RNA LUCAT1 enhances the survival and therapeutic effects of mesenchymal stromal cells post-myocardial infarction |
| title_full_unstemmed | Long noncoding RNA LUCAT1 enhances the survival and therapeutic effects of mesenchymal stromal cells post-myocardial infarction |
| title_short | Long noncoding RNA LUCAT1 enhances the survival and therapeutic effects of mesenchymal stromal cells post-myocardial infarction |
| title_sort | long noncoding rna lucat1 enhances the survival and therapeutic effects of mesenchymal stromal cells post myocardial infarction |
| topic | apoptosis MSC lncRNA myocardial infarction JMJD6 FOXQ1 |
| url | http://www.sciencedirect.com/science/article/pii/S2162253121003097 |
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