Downregulation of miR­138­5p promotes non­small cell lung cancer progression by regulating CDK8.

Dysregulation of microRNAs (miRNAs) is frequently observed during cancer development. Aberrant expression of miRNA­138­5p (miR­138­5p) has been found in many types of cancer. However, the role and the mechanisms underlying miR­138­5p function in non­small cell lung cancer (NSCLC) progression remain unknown. In the present study, miR­138­5p expression was identified to be decreased in tumor tissues compared with matched normal tissues from patients with NSCLC. In addition, low expression of miR­138­5p was detected in three NSCLC cell lines compared with a normal lung epithelium cell line. Moreover, CDK8 mRNA expression was increased in tumor tissues compared with matched normal tissues from patients with NSCLC, and an inverse association between miR­138­5p and CDK8 was observed. Furthermore, CDK8 was predicted to be a target of miR­138­5p. Dual luciferase assay confirmed that miR­138­5p could directly bind to the 3' untranslated region of CDK8 mRNA. In A549 cells, overexpression of miR­138­5p inhibited cell growth and significantly increased cell apoptosis rates and the number of cells in G0/G1 phase. Moreover, forced overexpression of CDK8 partially reversed miR­138­5p mimic­induced cell growth arrest and alteration of cell apoptosis and cell cycle. In conclusion, the present results suggested that miR­138­5p may be a tumor suppressor in NSCLC cells and a promising therapeutic target for treating patients with NSCLC.

Effects of blood pressure goals on cardiovascular outcomes in hypertensive patients.

INTRODUCTION: The aim of the study was to evaluate the effects of blood pressure (BP) goals on cardiovascular outcomes in hypertensive patients. MATERIAL AND METHODS: Primary hypertensive patients were retrospectively enrolled from outpatient clinics. The demographics, comorbidities, laboratory parameters and glomerular filtration rate (GFR) were collected. All participants were followed for 1 year. Cardiovascular outcomes included composite of all-cause mortality, non-fatal myocardial infarction, and non-fatal ischemic stroke/transient ischemic attack. Adverse event was defined as falling down and GFR decrease at follow-up. RESULTS: A total of 1226 patients were included. Based on therapeutic BP goals, participants were divided into low (< 130/80 mm Hg) and high (< 140/90 mm Hg) therapeutic goal groups and an uncontrolled hypertension (≥ 140/90 mm Hg) group. Compared to the low therapeutic goal group, patients in the uncontrolled group were older and more likely to be smokers, have longer duration of hypertension, diabetes mellitus, lower GFR and higher prevalent ischemic stroke (p < 0.05). Patients in the uncontrolled hypertension group had higher incidence of composite endpoints than low and high therapeutic goal groups. Two cases of falling down were observed in the low therapeutic goal group and no significant changes in GFR were observed. With adjustment for confounding factors, the uncontrolled hypertension group had higher risk of composite endpoints compared to low and high therapeutic goal groups, and these benefits were more prominent in the low versus high therapeutic goal group. CONCLUSIONS: In hypertension patients, when compared to uncontrolled hypertension patients, low therapeutic BP goal is associated with better cardiovascular outcomes than high therapeutic BP goal.