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.
Subject(s)
Humans , Atherosclerosis/genetics , Autophagy/genetics , Cell Cycle Proteins/metabolism , Endothelial Cells/metabolism , Endothelium/metabolism , MicroRNAs/metabolism , Repressor Proteins/metabolism , RNA Splicing Factors , Serine-Arginine Splicing Factors/genetics , RNA, Long Noncoding/metabolismABSTRACT
Objective@#The purpose of this study is to investigate the current status and associated factors of fatigue among adolescents in Suzhou and to provide reference for improving adolescent fatigue.@*Methods@#A general information questionnaire and the Fatigue Scale14 (FS-14) were administered among 16 109 junior high and senior high school students from 20 schools in six districts of four cities in Suzhou, using stratified cluster random sampling.@*Results@#The physical fatigue score, mental fatigue score and total fatigue score of the participants were (3.90±2.24) (2.26±1.71) and (6.16±3.56) points, respectively. Gender, grade, academic performance, study time, exercise frequency, exercise duration, whether from a single parent family, living environment, family members frequently reported fatigue, and social support from around showed associations with adolescent fatigue score by the multiple linear regression analysis(B=0.35, 1.16, -0.50, 0.50, -0.26, -0.27, 0.32, 0.31, 1.19, -0.49, P<0.01).@*Conclusion@#The fatigue scores of adolescents in Suzhou are relatively high. Special preventive measures should be formulated to reduce the impact of fatigue symptoms on adolescents.