Crosstalk between KIF1C and PRKAR1A in left atrial myxoma
Abstract Cardiac myxoma (CM) is the most common benign cardiac tumor, and most CMs are left atrial myxomas (LAMs). Six variations of KIF1C, c.899 A > T, c.772 T > G, c.352 A > T, c.2895 C > T, c.3049 G > A, and c.*442_*443dup in left atrial myxoma tissues are identified by whole-exome...
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| Format: | Article |
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Nature Portfolio
2023-07-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-023-05094-5 |
| _version_ | 1797778710589341696 |
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| author | Mengchen Zhou Yan Yao Xiangyi Wang Lingfeng Zha Yilin Chen Yanze Li Mengru Wang Chenguang Yu Yingchao Zhou Qianqian Li Zhubing Cao Jianfei Wu Shumei Shi Dan Jiang Deyong Long Jiangang Wang Qing Wang Xiang Cheng Yuhua Liao Xin Tu |
| author_facet | Mengchen Zhou Yan Yao Xiangyi Wang Lingfeng Zha Yilin Chen Yanze Li Mengru Wang Chenguang Yu Yingchao Zhou Qianqian Li Zhubing Cao Jianfei Wu Shumei Shi Dan Jiang Deyong Long Jiangang Wang Qing Wang Xiang Cheng Yuhua Liao Xin Tu |
| author_sort | Mengchen Zhou |
| collection | DOAJ |
| description | Abstract Cardiac myxoma (CM) is the most common benign cardiac tumor, and most CMs are left atrial myxomas (LAMs). Six variations of KIF1C, c.899 A > T, c.772 T > G, c.352 A > T, c.2895 C > T, c.3049 G > A, and c.*442_*443dup in left atrial myxoma tissues are identified by whole-exome sequencing (WES) and Sanger sequencing. RNA-seq and function experiments show the reduction of the expression of KIF1C and PRKAR1A caused by rare variations of KIF1C. KIF1C is observed to be located in the nucleus, bind to the promoter region of PRKAR1A, and regulate its transcription. Reduction of KIF1C decreases PRKAR1A expression and activates the PKA, which causes an increase in ERK1/2 phosphorylation and SRC-mediated STAT3 activation, a reduction of CDH1, TP53, CDKN1A, and BAX, and eventually promotes tumor formation both in vitro and in vivo. The results suggest that inhibition of KIF1C promotes the pathogenesis of LAM through positive feedback formed by the crosstalk between KIF1C and PRKAR1A. |
| first_indexed | 2024-03-12T23:21:27Z |
| format | Article |
| id | doaj.art-83f486472d1f49dfb3fb48742b0b4ccb |
| institution | Directory Open Access Journal |
| issn | 2399-3642 |
| language | English |
| last_indexed | 2024-03-12T23:21:27Z |
| publishDate | 2023-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj.art-83f486472d1f49dfb3fb48742b0b4ccb2023-07-16T11:25:09ZengNature PortfolioCommunications Biology2399-36422023-07-016111210.1038/s42003-023-05094-5Crosstalk between KIF1C and PRKAR1A in left atrial myxomaMengchen Zhou0Yan Yao1Xiangyi Wang2Lingfeng Zha3Yilin Chen4Yanze Li5Mengru Wang6Chenguang Yu7Yingchao Zhou8Qianqian Li9Zhubing Cao10Jianfei Wu11Shumei Shi12Dan Jiang13Deyong Long14Jiangang Wang15Qing Wang16Xiang Cheng17Yuhua Liao18Xin Tu19Department of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Cardiology, Beijing Anzhen Hospital, Capital Medical UniversityKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and TechnologyDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and TechnologyKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and TechnologyKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and TechnologyKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and TechnologyKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and TechnologyKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and TechnologyKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and TechnologyKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and TechnologyKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and TechnologyKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and TechnologyDepartment of Cardiology, Beijing Anzhen Hospital, Capital Medical UniversityDepartment of Cardiac Surgery, Beijing Anzhen Hospital, Capital Medical UniversityKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and TechnologyDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyDepartment of Cardiology, Union Hospital, Tongji Medical College, Huazhong University of Science and TechnologyKey Laboratory of Molecular Biophysics of Ministry of Education, College of Life Science and Technology, Center for Human Genome Research, Cardio-X Institute, Huazhong University of Science and TechnologyAbstract Cardiac myxoma (CM) is the most common benign cardiac tumor, and most CMs are left atrial myxomas (LAMs). Six variations of KIF1C, c.899 A > T, c.772 T > G, c.352 A > T, c.2895 C > T, c.3049 G > A, and c.*442_*443dup in left atrial myxoma tissues are identified by whole-exome sequencing (WES) and Sanger sequencing. RNA-seq and function experiments show the reduction of the expression of KIF1C and PRKAR1A caused by rare variations of KIF1C. KIF1C is observed to be located in the nucleus, bind to the promoter region of PRKAR1A, and regulate its transcription. Reduction of KIF1C decreases PRKAR1A expression and activates the PKA, which causes an increase in ERK1/2 phosphorylation and SRC-mediated STAT3 activation, a reduction of CDH1, TP53, CDKN1A, and BAX, and eventually promotes tumor formation both in vitro and in vivo. The results suggest that inhibition of KIF1C promotes the pathogenesis of LAM through positive feedback formed by the crosstalk between KIF1C and PRKAR1A.https://doi.org/10.1038/s42003-023-05094-5 |
| spellingShingle | Mengchen Zhou Yan Yao Xiangyi Wang Lingfeng Zha Yilin Chen Yanze Li Mengru Wang Chenguang Yu Yingchao Zhou Qianqian Li Zhubing Cao Jianfei Wu Shumei Shi Dan Jiang Deyong Long Jiangang Wang Qing Wang Xiang Cheng Yuhua Liao Xin Tu Crosstalk between KIF1C and PRKAR1A in left atrial myxoma Communications Biology |
| title | Crosstalk between KIF1C and PRKAR1A in left atrial myxoma |
| title_full | Crosstalk between KIF1C and PRKAR1A in left atrial myxoma |
| title_fullStr | Crosstalk between KIF1C and PRKAR1A in left atrial myxoma |
| title_full_unstemmed | Crosstalk between KIF1C and PRKAR1A in left atrial myxoma |
| title_short | Crosstalk between KIF1C and PRKAR1A in left atrial myxoma |
| title_sort | crosstalk between kif1c and prkar1a in left atrial myxoma |
| url | https://doi.org/10.1038/s42003-023-05094-5 |
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