ABSTRACT
OBJECTIVE: Emerging evidence has demonstrated vital regulation of circular RNAs (circRNAs) on tumorigenesis and progression of tumors. Abnormally expressed circRNAs hsa_circ_0005075 (circ_0005075) has been reported in several tumors. In this study, we aimed to explore the expression profiles, prognostic value, and potential function of circ_0005075 in colorectal cancer (CRC) PATIENTS AND METHODS: RT-PCR was used to detect the expression of circ_0005075 in both CRC tissues and cell lines. The associations between circ_0005075 expression and clinicopathological features and clinical prognosis were statistically analyzed. The effects of circ_0005075 on CRC cells were evaluated by Cell Counting Kit-8 (CCK-8), colony formation assays, Flow cytometer, and transwell assays. Western blot was performed to explore whether circ_0005075 modulated the Wnt/ß-catenin pathway. RESULTS: We observed that circ_0005075 expression was significantly up-regulated in both CRC tissues and cell lines. Then, clinical assays indicated that high circ_0005075 expression was significantly associated with histology/differentiation, depth of invasion, advanced TNM stage, and shorter overall survival and disease-free survival of CRC patients. Cellular studies indicated that circ_0005075 can enhance the proliferation, migration, and invasion capacities of CRC cells, thereby promoting tumor progression. Further mechanistic investigation showed that circ_0005075 displayed its tumor-promotive roles through activating Wnt/ß-catenin pathway. CONCLUSIONS: Our present data revealed circ_0005075 as a potential molecular marker and target for the prognosis and treatment of CRC patients.
Subject(s)
Colorectal Neoplasms/genetics , Gene Expression Regulation, Neoplastic , RNA, Circular/genetics , Wnt Signaling Pathway/genetics , Aged , Apoptosis/genetics , Cell Line, Tumor , Cell Proliferation/genetics , Colorectal Neoplasms/metabolism , Colorectal Neoplasms/mortality , Colorectal Neoplasms/pathology , Disease-Free Survival , Female , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Oncogenes , Prognosis , RNA, Small Interfering/genetics , TransfectionABSTRACT
To investigate the relationship between left atrial (LA) size, endothelial dysfunction and different markers of target organ damage (TOD), we measured left atrial diameter (LAD) and endothelial function in hypertensive patients with or without TOD. In this study, 197 patients with hypertension were divided into four groups as follows: no TOD (Group I, n=40), one TOD (Group II, n=76), two TOD (Group III, n=46) and ≥3 TOD (Group IV, n=35). Endothelial function was assessed by endothelium-dependent vasodilatation (flow-mediated dilation, FMD) of the brachial artery. We also assessed serum creatinine, the urinary albumin-creatinine ratio (UACR), the intima-media thickness (IMT) of the common carotid, carotid to femoral pulse wave velocity (cf-PWV) and left ventricular mass index (LVMI). Our results were as follows: LA size was increased in 50.8% of patients and was associated with the number of TOD. LAD was larger in the patient groups with ≥3 TOD as compared with patients with two TOD, one TOD and no TOD. FMD was lower in patients with LAD enlargement. LAD exhibited significant relationships with serum creatinine, UACR, cf-PWV, IMT and LVMI. In stepwise multivariate regression analysis, LVMI (ß=0.37, P<0.001), BMI (ß=0.33, P<0.001), duration of hypertension (ß=0.20, P=0.001) and FMD (ß=-0.17, P=0.006) were the independent predictors of LAD. FMD significantly correlated with LAD (ß=-0.26, P=0.001), male sex (ß=-0.23, P=0.004) and pulse pressure (PP) (ß=-0.16, P<0.05). In conclusions, enlargement of LAD may be an important predictor of endothelial dysfunction and may be considered to be an indicator for evaluating TOD in hypertensive patients.
Subject(s)
Asian People , Brachial Artery/physiopathology , Heart Atria/pathology , Hypertension/physiopathology , Adult , Albuminuria/physiopathology , Carotid Arteries/diagnostic imaging , Carotid Arteries/physiopathology , Carotid Intima-Media Thickness , Creatinine/blood , Creatinine/urine , Endothelium, Vascular/diagnostic imaging , Endothelium, Vascular/physiopathology , Female , Heart Atria/diagnostic imaging , Heart Atria/physiopathology , Humans , Hypertension/diagnostic imaging , Hypertension/epidemiology , Hypertrophy, Left Ventricular/diagnostic imaging , Hypertrophy, Left Ventricular/physiopathology , Male , Middle Aged , Organ Size , Prevalence , Vascular Stiffness/physiology , Vasodilation/physiologyABSTRACT
Recombinant adeno-associated viral (rAAV) vector-mediated overexpression of alpha-synuclein (alphaSyn) protein has been shown to cause neurodegeneration of the nigrostriatal dopaminergic pathway in rodents and primates. Using serotype-2 rAAV vectors, we recently reported the protective effect of Parkin on alphaSyn-induced nigral dopaminergic neurodegeneration in a rat model. Here we investigated the neuronal specificity of alphaSyn toxicity and the effect of Parkin co-expression in a primate model. We used another serotype (type-1) of AAV vector that was confirmed to deliver genes of interest anterogradely and retrogradely to neurons in rats. The serotype-1 rAAV (rAAV1) carrying alphaSyn cDNA (rAAV1-alphaSyn), and a cocktail of rAAV1-alphaSyn and rAAV1 carrying parkin cDNA (rAAV1-parkin) were unilaterally injected into the striatum of macaque monkeys, resulting in protein expression in striatonigral GABAergic and nigrostriatal dopaminergic neurons. Injection of rAAV1-alphaSyn alone decreased tyrosine hydroxylase immunoreactivity in the striatum compared with the contralateral side injected with a cocktail of rAAV1-alphaSyn and rAAV1-parkin. Immunostaining of striatonigral GABAergic neurons was similar on both sides. Overexpression of Parkin in GABAergic neurons was associated with less accumulation of alphaSyn protein and/or phosphorylation at Ser129 residue. Our results suggest that the toxicity of accumulated alphaSyn is not induced in non-dopaminergic neurons and that the alphaSyn-ablating effect of Parkin is exerted in virtually all neurons in primates.
