RESUMO
OBJECTIVES: Abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are involved in carotid artery stenosis. The purpose of this study was to investigate the diagnostic value of serum miR-28-5p in asymptomatic carotid artery stenosis and its regulation on the proliferation and migration of VSMCs. METHODS: Serum miR-28-5p levels in 65 healthy controls and 68 asymptomatic carotid artery stenosis patients were detected by qRT-PCR. The receiver-operating characteristic curve was applied to elucidate the diagnostic value of serum miR-28-5p for carotid artery stenosis patients. The specificity of miRNA targets was detected by luciferase reporter assay. CCK-8 and Transwell assay were applied to detect proliferation and migration of cells. Pearson correlation test was used to investigate the correlation between Forkhead box subclass O 1 (FOXO1) and serum miR-28-5p. RESULTS: Serum miR-28-5p was significantly reduced in asymptomatic carotid artery stenosis patients. Moreover, miR-28-5p could distinguish asymptomatic carotid artery stenosis patients from healthy controls, with sensitivity and specificity of 86.8% and 81.5%, respectively, indicating its high diagnostic value. The overexpression of miR-28-5p inhibited the proliferation and migration of VSMCs, while inhibition of miR-28-5p resulted in the opposite effect. What is more, FOXO1, a direct target of miR-28-5p, was significantly increased in asymptomatic carotid artery stenosis patients. Inhibition of miR-28-5p in VSMCs reversed the reduction of FOXO1 levels in patients. CONCLUSIONS: miR-28-5p is a valuable diagnostic biomarker for asymptomatic carotid artery stenosis and can affect the proliferation and migration of VSMCs by regulating FOXO1.
Assuntos
Estenose das Carótidas , MicroRNAs , Estenose das Carótidas/genética , Movimento Celular , Proliferação de Células , Células Cultivadas , Humanos , MicroRNAs/genética , Músculo Liso Vascular , Miócitos de Músculo LisoRESUMO
Circular RNA (circRNA), a recently identified endogenous non-coding RNA molecule, regulates gene expression in mammals. At the current stage, the expression and function of circRASSF2 in breast cancer (BC) have not been clarified. According to our study, it is found that circRASSF2 sequences contain miR-1205 binding sites, and Homeobox gene A1 (HOXA1) is the target gene of miR-1205. Besides, the clinical observations and histopathologic study reveal that the expression of circRASSF2 increased to a significant extent in BC tissues and serum. Additionally, it is found that circRASSF2 expression had a positive correlation with distant metastasis, lymph node metastasis, TNM stage, differentiation and tumor size, and that overall survival (OS) and progression-free survival (PFS) of circRASSF2 high expression BC patients were inferior to those with low circRASSF2 expression. In vitro study, an overt decrease was detected in the proliferation, clone formation ability, migration and invasion of breast cancer cells in cells when circRASSF2 was knocked down. We confirmed the direct interaction between circRASSF2, miR-1205 and HOXA1 by a dual luciferase reporter system. Additionally, our study revealed that over-expression of miR-1205 decreased HOXA1 protein expression, and HOXA1 protein expression decreased when circRASSF2 were knocked down, and when miR-1205 expression was inhibited, HOXA1 expression was significantly increased. In conclusion, our study suggests that circRASSF2 regulates BC progression through the miR-1205/HOXA1 pathway. Our findings suggest the prospect of circRASSF2 serving as therapeutic target as such to cure BC patients.