LOC100996425 acts as a promoter in prostate cancer by mediating hepatocyte nuclear factor 4A and the AMPK/mTOR pathway.

The involvement of long non-coding RNAs (lncRNAs), differentially expressed genes and signals in prostate cancer (PCa) continues to be a subject of investigation. This study determined effects of LOC100996425 on human PCa by targeting hepatocyte nuclear factor 4A (HNF4A) via the AMPK/mTOR pathway. PCa and adjacent normal tissues were obtained to characterize expression pattern of LOC100996425, HNF4A and the AMPK/mTOR pathway-related genes. Then, the target gene of LOC100996425 was determined with lncRNA target prediction website and further verification was obtained through luciferase assay and ribonucleoprotein immunoprecipitation. After that, PCa cells were introduced with LOC100996425, HNF4A, siLOC100996425 or siHNF4A to explore the specific significance of LOC100996425 and HNF4A in PCa. The mechanism associated with AMPK/mTOR pathway was investigated using AMPK inhibitor or activator. LOC100996425 was up-regulated, while HNF4A was down-regulated in the PCa tissues. HNF4A was a target gene of LOC100996425. PCa cells transfected with either siLOC100996425 or HNF4A displayed reduced rates of PCa cell proliferation and migration while elevating cell apoptosis. HNF4A overexpression reversed the promotive effect of LOC100996425 overexpression on PCa. The activation of AMPK pathway involved in the cancer progression mediated by LOC100996425. Down-regulation of LOC100996425 retards progression of PCa through HNF4A-mediated AMPK/mTOR pathway.

Long non-coding RNA LINC00152 promotes cell growth and invasion of papillary thyroid carcinoma by regulating the miR-497/BDNF axis.

Long intergenic non-coding RNA 152 (LINC00152) was reported to be tightly linked to tumorigenesis and progression in multiple cancers. However, its biological role and modulatory mechanism in papillary thyroid carcinoma (PTC) has not been elucidated. In this study, we determined the expression levels of LINC00152 in PTC tissues and cell lines by quantitative real time polymerase chain reaction (qRT-PCR). Cell proliferation, colony formation, migration, and invasion were measured by a Cell Counting Kit-8 assay, colony formation analysis, wound healing, and transwell invasion assay, respectively. A luciferase reporter assay and qRT-PCR were used to determine whether LINC00152 interacts with miR-497 directly. We established a xenograft mouse model to examine the underlying molecular mechanism and effect of LINC00152 on tumor growth in vivo. We found that LINC00152 expression was significantly increased in PTC tissues and derived cell lines. LINC00152 knockdown significantly inhibited proliferation, colony formation, migration, and invasion in vitro, and impaired tumor growth in vivo. We revealed that LINC00152 functioned as a competing endogenous RNA to the miR-497 sponge, downregulating its downstream target brain-derived neurotrophic factor (BDNF), which is an oncogene in thyroid cancer. These findings suggest that LINC00152 is responsible for PTC cell proliferation and invasion and exerts its function by regulating the miR-497/BDNF axis.

Development and validation of a sensitive UHPLC-MS/MS method for quantitative analysis of farrerol in rat plasma: Application to pharmacokinetic and bioavailability studies.

Farrerol is a 2,3-dihydro-flavonoid isolated from rhododendron. In this study, a sensitive and selective ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method was developed for the determination of farrerol in rat plasma. Liquid-liquid extraction by ethyl ether was used for sample preparation. Chromatographic separation was achieved on an Agilent UHPLC XDB-C18 column (2.1 × 100 mm, 1.8 µm) with water and methanol (30:70, v/v) as the mobile phase. An electrospray source was applied and operated in negative ion mode; selection reaction monitoring was used for quantification using target fragment ions m/z 299 → 179 for farrerol and m/z 267 → 252 for internal standard. Calibration plots were linear in the range of 2.88-1440 ng/mL for farrerol in rat plasma. Intra- and inter-day precisions were <11.6%, and the accuracy ranged from -13.9 to 11.9%. The UHPLC-MS/MS method was successfully applied in pharmacokinetics and bioavailability studies of farrerol in rats.

The role of microRNA-572 in the proliferation and chemotherapeutic treatment of prostate cancer.

OBJECTIVE: MicroRNAs (miRNAs) regulate prostate tumorigenesis and progression by involving different molecular pathways. In this study, we examined the role of miR-572 in prostate cancer (PCa). METHODS: The proliferation rates of LNCaP and PC-3 PCa cells were studied using MTT assays. Transwell migration and Matrigel invasion assays were performed to evaluate cell migration and invasion, respectively. Protein expression levels were examined using western blotting. Docetaxel-induced apoptosis was evaluated by Caspase-Glo3/7 assays. The putative miR-572 binding site in the phosphatase and tensin homolog (PTEN) 3' untranslated region (3' UTR) was assessed with dual-luciferase reporter assays. Additionally, miR-572 expression levels in human PCa tissues were examined by qRT-PCR assays. RESULTS: Upregulation of miR-572 promoted proliferation, migration, and invasion of PCa cells. Overexpression of miR-572 decreased sensitivity of PCa cells to docetaxel treatment by reducing docetaxel-induced apoptosis. MiR-572 can regulate migration and invasion in PCa cells. Furthermore, miR-572 could regulate expression of PTEN and p-AKT in PCa cells by directly binding to the PTEN 3' UTR. MiR-572 expression levels were increased in human PCa tissues and associated with PCa stage. CONCLUSIONS: miR-572 displayed essential roles in PCa tumor growth and its expression level may be used to predict docetaxel treatment in these tumors.

Effects of propofol on human cholangiocarcinoma and the associated mechanisms.

Cholangiocarcinoma (CCA) is the most common type of biliary duct malignancy. Propofol is a fast-acting intravenous anesthetic, which also exerts an anti-cancer effect. The aim of the current study was to explore the effects of propofol on human CCA and the associated mechanisms in vitro. The results indicated that as concentration (0, 1, 5 and 10 µg/ml) of propofol and treatment time (24, 48 and 72 h) increased, the cell inhibition rate of human CCA QBC939 cells increased. Furthermore, treatment with various concentrations of propofol for 48 h resulted in a decrease in migration and invasion capacity in QBC939 cells. Propofol also induced the apoptosis of QBC939 cells and cell cycle arrest in G1 phase. Propofol treatment increased the expression level of Bax and decreased that of Bcl-2. In addition, the effects of propofol on gene expression were evaluated, including Wnt3α, ß-catenin, Snail1 and c-myc in the Wnt/ß-catenin signaling pathway. It was identified that as the concentration of propofol increased, the expression of these genes decreased. In conclusion, the current results indicate that propofol is a promising therapeutic agent for the treatment of CCA.

Serum PLR and LMR in Behçet's disease: Can they show the disease activity?

The aim of this study is to determine platelet to lymphocyte ratio (PLR) and lymphocytes to monocytes ratio (LMR) levels in Behçet's disease (BD) and to investigate their relationships with disease activity.Hematological and inflammatory parameters including high-sensitivity C-reactive proteins (hs-CRP), erythrocyte sedimentation rate (ESR), PLR, and LMR were examined in BD and healthy controls.Data from 140 patients with BD (108 with active and 32 with inactive disease) and 107 controls were enrolled. PLR (153.21 ±â€Š65.44, 106.20 ±â€Š28.91, P <.001, respectively) was remarkably higher, whereas LMR (5.37 ±â€Š5.47, 8.95 ±â€Š5.84, P <.001, respectively) was significantly lower in BD than in controls. Active BD patients had significantly higher PLR (159.20 vs 131.14, P = .037), ESR (38.30 vs 24.55, P = .017), and hs-CRP (30.20 vs 17.21, P = .027) than those with inactive BD. However, no significant difference in LMR was found between the groups. Moreover, PLR was positively correlated with BDCAF (r = 0.193, P <.05), hs-CRP (r = 0.402, P <.01), and ESR (r = 0.284, P <.01), whereas LMR was negatively correlated with BDCAF (r = -0.175, P <.05), hs-CPR (r = -0.263, P <.01), and ESR (r = -0.175, P <.05). Additionally, both PLR and LMR were shown to be independent factors for BD by multivariate logistic regression analysis. Furthermore, a PLR level of 124.63 was determined as the best cut-off value by ROC analysis (sensitivity 64.3%, specificity 78.0%, and the area under the ROC curve 0. 753).PLR was elevated in active BD as compared to inactive BD. PLR may be a reliable, cost-effective, and novel potential parameter to help evaluate disease activity in BD.

Prognostic value of platelet to lymphocyte ratio in hepatocellular carcinoma: a meta-analysis.

This study was designed to evaluate the prognostic value of platelet to lymphocyte ratio (PLR) in hepatocellular carcinoma (HCC). A comprehensive literature search for relevant studies was performed in Web of science, Embase and Pubmed. A total of nine studies with 2017 patients were included in this meta-analysis, and combined hazard ratio (HR) or odds ratio (OR) and 95% confidence intervals (95%CIs) were served as effect measures. Pooled results showed that elevated PLR was associated with poor overall survival (OS) (HR = 1.63, 95%CI: 1.42-1.88, p = 0.000; I2 = 0.0%, Ph = 0.637) and poor disease-free survival (DFS)/recurrence-free survival (RFS) (HR=1.32, 95%CI: 1.15-1.52, p = 0.000; I2 = 19.3%, Ph = 0.287) in HCC patients. In addition, high PLR was not significantly correlated with the presence of vascular invasion, tumor multifocality, poor tumor grade or high level of serum AFP (>400 ng/ml). In conclusion, elevated PLR indicated a poor prognosis for patients with HCC. PLR may be a reliable, easily-obtained, and low cost biomarker with prognostic potential for HCC.