Crosstalk between KIF1C and PRKAR1A in left atrial myxoma
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Published:2023-07-14
Issue:1
Volume:6
Page:
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ISSN:2399-3642
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Container-title:Communications Biology
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language:en
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Short-container-title:Commun Biol
Author:
Zhou MengchenORCID, Yao YanORCID, Wang Xiangyi, Zha Lingfeng, Chen Yilin, Li Yanze, Wang Mengru, Yu Chenguang, Zhou Yingchao, Li Qianqian, Cao Zhubing, Wu Jianfei, Shi Shumei, Jiang Dan, Long Deyong, Wang Jiangang, Wang Qing, Cheng Xiang, Liao YuhuaORCID, Tu XinORCID
Abstract
AbstractCardiac 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.
Funder
National Natural Science Foundation of China Fundamental Research Funds for the Central Universitie Scientific Research Key Program of Beijing Municipal Commission of Education
Publisher
Springer Science and Business Media LLC
Subject
General Agricultural and Biological Sciences,General Biochemistry, Genetics and Molecular Biology,Medicine (miscellaneous)
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