SMILR Aggravates the Progression of Atherosclerosis by Sponging miR-10b-3p to Regulate KLF5 Expression
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ORIGINAL ARTICLE
SMILR Aggravates the Progression of Atherosclerosis by Sponging miR-10b-3p to Regulate KLF5 Expression Huaqing Li,1 Zhiyu Pan,1,2 Qian Chen,1 Zhen Yang,1 and Dongbing Zhang1
Over the past few decades, long noncoding RNAs (lncRNAs) have been widely accepted to be involved in various diseases, and smooth muscle enriched long noncoding RNA (SMILR) was reported to participate in the proliferation of vascular smooth muscle cells (VSMCs). Nevertheless, the molecular mechanisms of SMILR in atherosclerosis (AS) have not been fully explored. In this study, VSMCs and human mononuclear cells (U937) treated with oxidized low-density lipoprotein (ox-LDL) were used as cell models of AS. We found that the expression of SMILR was upregulated in the serum of AS patients and ox-LDL-induced AS cell models. SMILR knockdown inhibited cell proliferation while increasing cell apoptosis in the AS cell models. In addition, SMILR acted as a sponge for miR-10b-3p, and miR-10b-3p counteracted SMILR-mediated regulation of AS. Moreover, we confirmed that miR-10b-3p could bind with KLF5, and SMILR regulated KLF5 expression by competitively binding miR-10b-3p. Furthermore, miR-10b-3p modulated cell proliferation and apoptosis in AS by targeting KLF5. Finally, miR-10b-3p regulated AS progression in vivo by targeting KLF5. Overall, our study demonstrated that SMILR participated in the progression of AS by targeting the miR-10b-3p/KLF5 axis, which may provide some clues for future studies of AS.
Abstract—
KEY WORDS: SMILR; miR-10b-3p; KLF5; AS.
INTRODUCTION Atherosclerosis (AS) is the leading cause of various diseases, such as cerebral infarction, coronary heart disease, and peripheral artery disease [5, 30, 32]. AS is an inflammatory disease that usually occurs in adolescence and is aggravated with the increase in age [24]. Although AS has been studied extensively, the morbidity and 1
Department of Vascular Surgery, Minhang Hospital, Fudan University, No. 39 Xinling Road, Minhang District, 201199, Shanghai, China 2 To whom correspondence should be addressed at Department of Vascular Surgery, Minhang Hospital, Fudan University, No. 39 Xinling Road, M i n h a n g D i s t r i c t , 2 0 11 9 9 , S h a n g h a i , C h i n a . E - m a i l : [email protected]
mortality still remain very high worldwide [20]. Therefore, it is very urgent to determine novel biomarkers and investigate their molecular regulatory mechanisms in AS. With a length of more than 200 nucleotides, long noncoding RNAs (lncRNAs) play an important role in various disease processes, such as cell growth, proliferation, apoptosis, differentiation, and other biological processes [3, 15]. Increasing studies have reported that lncRNAs play significant roles in various human diseases. For example, lncRNA small nucleolar RNA host gene 1 (SNHG1) accelerates non-small cell lung cancer progression by sponging miR-497 [14]. lncRNA growth arrest– specific transcript 5 (GAS5) is upregulated in patients with Klinefelter syndrome [21]. lncRNA metastasis-associated lung adenocar
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