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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

邮发代号 80-967

2019 Impact Factor: 3.421

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Frontiers of Medicine  2023, Vol. 17 Issue (2): 317-329   https://doi.org/10.1007/s11684-022-0931-4
  本期目录
lncR-GAS5 upregulates the splicing factor SRSF10 to impair endothelial autophagy, leading to atherogenesis
Yuhua Fan1,2, Yue Zhang1,3, Hongrui Zhao1, Wenfeng Liu1, Wanqing Xu1, Lintong Jiang1, Ranchen Xu1, Yue Zheng1, Xueqing Tang1, Xiaohan Li1, Limin Zhao1, Xin Liu1, Yang Hong1, Yuan Lin1, Hui Chen1, Yong Zhang1()
1. Department of Pharmacology, State–Province Key Laboratories of Biomedicine-Pharmaceutics of China, Key Laboratory of Cardiovascular Medicine Research, Ministry of Education, College of Pharmacy, Harbin Medical University, Harbin 150081, China
2. Department of Pathology and Pathophysiology, College of Basic Medical Sciences, Harbin Medical University-Daqing, Daqing 163319, China
3. Center for Drug Research and Development, Guangdong Pharmaceutical University, Guangzhou 510006, China
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Abstract：

Long noncoding RNAs (lncRNAs) play a critical role in the regulation of atherosclerosis. Here, we investigated the role of the lncRNA growth arrest-specific 5 (lncR-GAS5) in atherogenesis. We found that the enforced expression of lncR-GAS5 contributed to the development of atherosclerosis, which presented as increased plaque size and reduced collagen content. Moreover, impaired autophagy was observed, as shown by a decreased LC3II/LC3I protein ratio and an elevated P62 level in lncR-GAS5-overexpressing human aortic endothelial cells. By contrast, lncR-GAS5 knockdown promoted autophagy. Moreover, serine/arginine-rich splicing factor 10 (SRSF10) knockdown increased the LC3II/LC3I ratio and decreased the P62 level, thus enhancing the formation of autophagic vacuoles, autolysosomes, and autophagosomes. Mechanistically, lncR-GAS5 regulated the downstream splicing factor SRSF10 to impair autophagy in the endothelium, which was reversed by the knockdown of SRSF10. Further results revealed that overexpression of the lncR-GAS5-targeted gene miR-193-5p promoted autophagy and autophagic vacuole accumulation by repressing its direct target gene, SRSF10. Notably, miR-193-5p overexpression decreased plaque size and increased collagen content. Altogether, these findings demonstrate that lncR-GAS5 partially contributes to atherogenesis and plaque instability by impairing endothelial autophagy. In conclusion, lncR-GAS5 overexpression arrested endothelial autophagy through the miR-193-5p/SRSF10 signaling pathway. Thus, miR-193-5p/SRSF10 may serve as a novel treatment target for atherosclerosis.
Key words： lncR-GAS5    miR-193-5p    splicing factor SRSF10    autophagy    atherogenesis
收稿日期: 2022-01-06      出版日期: 2023-05-26
Corresponding Author(s): Yong Zhang   
 引用本文:   
. [J]. Frontiers of Medicine, 2023, 17(2): 317-329.
Yuhua Fan, Yue Zhang, Hongrui Zhao, Wenfeng Liu, Wanqing Xu, Lintong Jiang, Ranchen Xu, Yue Zheng, Xueqing Tang, Xiaohan Li, Limin Zhao, Xin Liu, Yang Hong, Yuan Lin, Hui Chen, Yong Zhang. lncR-GAS5 upregulates the splicing factor SRSF10 to impair endothelial autophagy, leading to atherogenesis. Front. Med., 2023, 17(2): 317-329.
 链接本文:  
https://academic.hep.com.cn/fmd/CN/10.1007/s11684-022-0931-4
https://academic.hep.com.cn/fmd/CN/Y2023/V17/I2/317
Primer name Sequences (5′–3′)
lncR-GAS5 Forward:5′-GTGTCCCCAAGGAAGGATGA-3′
Reverse:5′-ACCAGGAGCAGAACCATTAAGC-3′
CD31 Forward:5′-ACGCTGGTGCTCTATGCAAG-3′
Reverse:5′-TCAGTTGCTGCCCATTCATCA-3′
smMHC Forward:5′-AAGCTGCGGCTAGAGGTCA-3′
Reverse:5′-CCCTCCCTTTGATGGCTGAG-3′
IGF2 Forward:5′-GGGTGGGTAGAGCAATCAGG-3′
Reverse:5′-GGGCAAGTTCTTCCAATATGAC-3′
ACVR1 Forward:5′-TTCTGCTACGCCGTGGTC-3′
Reverse:5′-AAAGCCAAGGAAGGGAGG-3′
PRPS1 Forward:5′-CGTTGTTGATGCGAGAAA-3′
Reverse:5′-ATGGTGCTTGTGGGAGAT-3′
SRSF10 Forward:5′-TTCTGCTACGCCGTGGTC-3′
Reverse:5′-AAAGCCAAGGAAGGGAGG-3′
HOXA1 Forward:5′-AGGCTCTGGTGCTCCTGTCC-3′
Reverse:5′-CGCTCCCGCTGTTTACTC-3′
COL1A1 Forward:5′-AATCCATCGGTCATGCTCT-3′
Reverse:5′-TGCCATCAAAGTCTTCTGC-3′
MAP1LC3B Forward:5′-TTATAGAGCGATACAAGGGGGAG-3′
Reverse:5′-CGCCGTCTGATTATCTTGATGAG-3′
P62 Forward:5′-GACTGGCACCGCTACAACC-3′
Reverse:5′-CGTTGAAGGTGGCGAACTTCT-3′
GAPDH Forward:5′-AAGAAGGTGGTGAAGCAGGC-3′
Reverse:5′-TCCACCACCCAGTTGCTGTA-3′
miR-9 Forward:5′-CTAACGCTGCCGGAGATTAC-3′
Reverse:5′-TACTTGCCGCGCTTAAGATT-3′
miR-22 Forward:5′-CGGGCAGTTCTTCAGTGGCA-3′
Reverse:5′-CAGCCACAAAAGAGCACAAT-3′
miR-31 Forward:5′-CGGGCAGGCAAGATGCTGG-3′
Reverse:5′-CAGCCACAAAAGAGCACAAT-3′
miR-193-5p Forward:5′-CGGGCTGGGTCTTTGCGGGC-3′
Reverse:CAGCCACAAAAGAGCACAAT-3′
miR-222 Forward:5′-CGGGCCTCAGTAGCCAGTGT-3′
Reverse:5′-CAGCCACAAAAGAGCACAAT-3′
U6 Forward:5′-GCTTCGGCAGCACATATACTAAAAT-3′
Reverse:5′-CGCTTCACGAATTTGCGTGTCAT-3′
Tab.1  
Fig.1  
Fig.2  
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Fig.7  
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