Exploring the role of circ-GALK2 in vascular smooth muscle cell calcification: mechanisms and implications
Abstract Background Vascular calcification is associated with atherosclerosis, plaque destabilization and related cardiovascular risk/mortality. A key cell type involved in vascular calcification is the vascular smooth muscle cell (VSMC). Although several studies have reported the role of non-coding...
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BMC
2025-08-01
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| Series: | European Journal of Medical Research |
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| Online Access: | https://doi.org/10.1186/s40001-025-03040-1 |
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| author | Tianhui Jin Yehong Liu Gangjun Zong Ying Sheng Ruijiao Kong Xinyi Hu Hui Li Li Wang Liang Chen |
| author_facet | Tianhui Jin Yehong Liu Gangjun Zong Ying Sheng Ruijiao Kong Xinyi Hu Hui Li Li Wang Liang Chen |
| author_sort | Tianhui Jin |
| collection | DOAJ |
| description | Abstract Background Vascular calcification is associated with atherosclerosis, plaque destabilization and related cardiovascular risk/mortality. A key cell type involved in vascular calcification is the vascular smooth muscle cell (VSMC). Although several studies have reported the role of non-coding RNAs in regulating vascular calcification, the expressions and functions of certain circular RNAs in vascular calcification have not yet been fully explored. This study aimed to identify the differentially expressed circRNAs involved in the calcification of VSMCs and explore the regulatory function and molecular mechanism of certain circRNA. Methods and results High-throughput sequencing and qRT‒PCR revealed that circ-GALK2 (hsa_circ_0008488), a circular RNA generated from the GALK2 gene, was prominently upregulated in calcified VSMCs. Gain-of-function studies indicated that the overexpression of circ-GALK2 promoted VSMC calcification in vitro. We investigated the mechanism of circ-GALK2 as a microRNA sponge and noted that miR-134-3p and CD36 are downstream targets of circ-GALK2. The overexpression of circ-GALK2 promoted VSMC calcification by sponging miR-134-3p and increasing CD36 expression. The above effects were neutralized by the overexpression of miR-134-3p. We also confirmed the expression of the circ-Galk2/miR-134-3p/Cd36 axis in a mouse aortic calcification model. In addition, we investigated the relationship between plasma circ-GALK2 expression and human aortic calcification. Conclusions The current study elucidates the unique expression and critical function of the circ-GALK2/miR-134-3p/CD36 axis in vascular smooth muscle calcification, potentially offering significant insights for developing strategies to mitigate the progression of vascular calcification disease. Furthermore, this axis is anticipated to serve as a biomarker and a prospective therapeutic target for vascular calcification. Graphical Abstract |
| format | Article |
| id | doaj-art-04e0beff7e1e47db8e763b490674b05a |
| institution | DOAJ |
| issn | 2047-783X |
| language | English |
| publishDate | 2025-08-01 |
| publisher | BMC |
| record_format | Article |
| series | European Journal of Medical Research |
| spelling | doaj-art-04e0beff7e1e47db8e763b490674b05a2025-08-20T03:07:20ZengBMCEuropean Journal of Medical Research2047-783X2025-08-0130111310.1186/s40001-025-03040-1Exploring the role of circ-GALK2 in vascular smooth muscle cell calcification: mechanisms and implicationsTianhui Jin0Yehong Liu1Gangjun Zong2Ying Sheng3Ruijiao Kong4Xinyi Hu5Hui Li6Li Wang7Liang Chen8Department of Cardiology, The 904th Hospital of the Chinese PLA Joint Logistic Support ForceDepartment of Cardiology, The 904th Hospital of the Chinese PLA Joint Logistic Support ForceDepartment of Cardiology, The 904th Hospital of the Chinese PLA Joint Logistic Support ForceDepartment of Cardiology, The 904th Hospital of the Chinese PLA Joint Logistic Support ForceDepartment of Laboratory Diagnosis, Shanghai Fourth People’s Hospital Affiliated to Tongji UniversityDepartment of Cardiology, Wuxi Clinical College of Anhui Medical UniversityDepartment of Cardiology, Wuxi Clinical College of Anhui Medical UniversityDepartment of Cardiology, The 904th Hospital of the Chinese PLA Joint Logistic Support ForceDepartment of Cardiology, The 904th Hospital of the Chinese PLA Joint Logistic Support ForceAbstract Background Vascular calcification is associated with atherosclerosis, plaque destabilization and related cardiovascular risk/mortality. A key cell type involved in vascular calcification is the vascular smooth muscle cell (VSMC). Although several studies have reported the role of non-coding RNAs in regulating vascular calcification, the expressions and functions of certain circular RNAs in vascular calcification have not yet been fully explored. This study aimed to identify the differentially expressed circRNAs involved in the calcification of VSMCs and explore the regulatory function and molecular mechanism of certain circRNA. Methods and results High-throughput sequencing and qRT‒PCR revealed that circ-GALK2 (hsa_circ_0008488), a circular RNA generated from the GALK2 gene, was prominently upregulated in calcified VSMCs. Gain-of-function studies indicated that the overexpression of circ-GALK2 promoted VSMC calcification in vitro. We investigated the mechanism of circ-GALK2 as a microRNA sponge and noted that miR-134-3p and CD36 are downstream targets of circ-GALK2. The overexpression of circ-GALK2 promoted VSMC calcification by sponging miR-134-3p and increasing CD36 expression. The above effects were neutralized by the overexpression of miR-134-3p. We also confirmed the expression of the circ-Galk2/miR-134-3p/Cd36 axis in a mouse aortic calcification model. In addition, we investigated the relationship between plasma circ-GALK2 expression and human aortic calcification. Conclusions The current study elucidates the unique expression and critical function of the circ-GALK2/miR-134-3p/CD36 axis in vascular smooth muscle calcification, potentially offering significant insights for developing strategies to mitigate the progression of vascular calcification disease. Furthermore, this axis is anticipated to serve as a biomarker and a prospective therapeutic target for vascular calcification. Graphical Abstracthttps://doi.org/10.1186/s40001-025-03040-1Circular RNAMicroRNACD36Vascular calcificationVascular smooth muscle |
| spellingShingle | Tianhui Jin Yehong Liu Gangjun Zong Ying Sheng Ruijiao Kong Xinyi Hu Hui Li Li Wang Liang Chen Exploring the role of circ-GALK2 in vascular smooth muscle cell calcification: mechanisms and implications European Journal of Medical Research Circular RNA MicroRNA CD36 Vascular calcification Vascular smooth muscle |
| title | Exploring the role of circ-GALK2 in vascular smooth muscle cell calcification: mechanisms and implications |
| title_full | Exploring the role of circ-GALK2 in vascular smooth muscle cell calcification: mechanisms and implications |
| title_fullStr | Exploring the role of circ-GALK2 in vascular smooth muscle cell calcification: mechanisms and implications |
| title_full_unstemmed | Exploring the role of circ-GALK2 in vascular smooth muscle cell calcification: mechanisms and implications |
| title_short | Exploring the role of circ-GALK2 in vascular smooth muscle cell calcification: mechanisms and implications |
| title_sort | exploring the role of circ galk2 in vascular smooth muscle cell calcification mechanisms and implications |
| topic | Circular RNA MicroRNA CD36 Vascular calcification Vascular smooth muscle |
| url | https://doi.org/10.1186/s40001-025-03040-1 |
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