RESUMO
Lung cancer is a common cancer that is familiar to people and has the highest global incidence; among all lung cancer patients, 85% are non-small cell lung cancer (NSCLC). A number of microRNAs (miRNAs), including miR-532-5p, are implicated in the pathophysiological processes of tumorigenesis. However, the mechanism of miR-532-5p in NSCLC remains unclear. In the current study, the expression of miR-532-5p was found to be markedly downregulated in clinical NSCLC tissues and cell lines. Further study indicated that ectopic expression of miR-532-5p inhibited NSCLC cell proliferation and invasion while accelerating in vitro, but silencing miR-532-5p had an opposite result. Furthermore, functional experiments revealed that miR-532-5p effectively blocked tumor growth in a xenograft tumor mouse model. Bioinformatics and luciferase reporter analysis verified that Yin Yang 1 (YY1) transcripts are targets of miR-532-5p. Moreover, the expression of YY1 was negatively regulated by miR-532-5p in NSCLC cells. In vivo assays indicated that downregulation of YY1 inhibited tumor growth. Notably, overexpression of YY1 effectively counteracted the tumor-suppressing effects of miR-532-5p in vitro and in vivo. In summary, this study demonstrated the tumor-suppressive role of miR-532-5p in NSCLC by regulating YY1 in vitro and in vivo.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Camundongos , MicroRNAs/genética , MicroRNAs/metabolismo , Yin-YangRESUMO
BACKGROUND: Worldwide, hypertension is an important public health challenge because of its high prevalence and the concomitant risks of cardiovascular disease. It induces half of the coronary heart disease and approximately two-thirds of the cerebrovascular disease burden. Vascular endothelial dysfunction has important roles in the pathophysiology of essential hypertension. Types I and II hypertension can be treated with sang-qi granules (SQG), a Chinese herbal formula. Several experimental studies on animals have shown that SQG can lower blood pressure and myocardial fibrosis by suppressing inflammatory responses. However, no standard clinical trial has confirmed this. Whether SQG can improve endothelial cell function is unknown. METHODS/DESIGN: In this randomized double-blind double-simulation controlled trial, 300 patients with stage I or II hypertension will be recruited and randomly allocated in a 1:1:1 ratio to group A (treatment with SQG and placebo instead of Losartan), group B (treatment with Losartan and placebo instead of SQG), and group C (treatment with SQG and Losartan). In this study, 10 g of SQG (or its placebo) will be administrated twice a day and 50 mg of Losartan (or its placebo) will be administrated once in the morning. The primary endpoint is the drug efficiency for each of the three groups. The secondary endpoints are the change in average systolic and diastolic blood pressure during the day and the night, the change in the rate at which blood pressure drops at night, assessment of target organ damage (heart rate variability, ankle-brachial pressure index, and pulse wave velocity), assessment of any improvement in symptoms (Hypertension Symptom Scale, syndrome integral scale in traditional Chinese medicine, Pittsburgh Sleep Quality Index Scale, Self-Rating Anxiety Scale, Self-Rating Depression Scale, and the 36-Item Short Form Health Survey), blood lipids, serum indicators of vascular function (changes in serum levels of ET-1, TXA2, NO, and PGI2), and safety indicators. DISCUSSION: This study aims to provide clinical evidence on the efficacy and safety of SQG in the treatment of hypertension. Moreover, the possible mechanism by which SQG may lower blood pressure will be explored by observing the protective effect of SQG on vascular endothelial function, as well as its effect on related clinical symptoms, risk factors, and the target organs of hypertension. TRIAL REGISTRATION: Chinese Clinical Trials Registry, ChiCTR1800016427. Registered on 1 June 2018.