MiR-186 targets ROCK1 to suppress the growth and metastasis of NSCLC cells.

MicroRNAs (miRNAs) act as oncogenes or tumor suppressors in human cancers. Increasing evidence shows that deregulation of miRNAs contributes to the development and progression of human non-small cell lung cancer (NSCLC). Here, we identified miR-186 as a tumor suppressor in NSCLC, which was decreased in NSCLC. Overexpression of miR-186 significantly inhibited proliferation, migration, and invasion of NSCLC cells. In addition, Rho-associated protein kinase 1 (ROCK1) was identified as a target of miR-186 in NSCLC cells. Restoration of ROCK1 remarkably reversed the tumor-suppressive effects of miR-186 on cell proliferation, migration, and invasion in NSCLC cells. Furthermore, ROCK1 was inversely correlated with miR-186 expression in NSCLC. Collectively, our data indicate that miR-186 functions as tumor suppressor in NSCLC by targeting ROCK1.

Feeding habits and habitats preferences affecting mercury bioaccumulation in 37 subtropical fish species from Wujiang River, China.

The present study is the first to report the total mercury concentration of 37 fish species collected from Wujiang River, which is the largest branch on the southern bank of Yangtze River, China and proposed for hydropower development. Total mercury concentrations varied among the 37 subtropical species examined. We found higher mercury concentrations in carnivorous species demonstrating greater mercury bioaccumulation in species with more predatory feeding habits. There is no significant difference between fish grouped by habitat preference and feeding habit. However, carnivorous species preferring benthic positions had higher total mercury concentrations than others suggesting that mercury accumulation is related to the interaction of feeding habit and habitat preference. In our study, fish that are bottom living and feed on other fish or aquatic animals are more likely at high risk of mercury exposure. Additional mercury contamination and future impoundment may raise mercury concentration in fish in the Wujiang causing concern for human health and ecological impacts.

A meta-analysis of the association between BRAF mutation and nonsmall cell lung cancer.

BACKGROUND: Previous studies investigating the association between BRAF mutations and nonsmall cell lung cancer (NSCLC) remain controversial. To address the issue, we performed an updated meta-analysis of related articles. METHODS: We conducted a comprehensive literature search in the electronic databases including ISI Science Citation Index, EMBASE, PubMed, and CNKI (up to January 2016). The odds ratios (ORs) and 95% confidence interval (CI) were assessed based on random-effects or fixed-effects models according to the heterogeneity of eligible studies. RESULTS: A total of 16 studies enrolled 11,711 patients with NSCLC were involved in the meta-analysis. The overall BRAF mutation rate was 2.6% (303/11,711). There was a significant association between BRAF mutations and adenocarcinomas (ADCs) in NSCLC compared with non-ADCs (OR = 3.96, 95% CI = 2.13-7.34, P < 0.0001). No significant difference was observed in smoking and stage in patients with BRAF mutations. However, a significant difference of BRAF mutation rate was observed between women and men (OR = 0.72, 95% CI = 0.55-0.95, P = 0.02). In addition, the BRAF mutations were more frequent in women (OR = 0.45, 95% CI = 0.26-0.77, P = 0.004) and never smokers (OR = 0.12, 95% CI = 0.05-0.29, P < 0.00001). CONCLUSIONS: BRAF mutations in ADCS and female significantly increased the risk of NSCLC compared to non-ADCS and male, respectively. BRAFV mutation in NSCLC patients was significantly associated with female and nonsmokers.

Original Research: miR-194 inhibits proliferation and invasion and promotes apoptosis by targeting KDM5B in esophageal squamous cell carcinoma cells.

Increasing evidence suggests that miR-194 is down-regulated in esophageal squamous cell carcinoma tumor tissue. However, the role and underlying mechanism of miR-194 in esophageal squamous cell carcinoma have not been well defined. We used DIANA, TargetScan and miRanda to perform target prediction analysis and found KDM5B is a potential target of miR-194. Based on these findings, we speculated that miR-194 might play a role in esophageal squamous cell carcinoma development and progression by regulation the expression of KDM5B. We detected the expression of miR-194 and KDM5B by quantitative real-time reverse transcription PCR (qRT-PCR) and Western blot assays, respectively, and found down-regulation of miR-194 and up-regulation of KDM5B existed in esophageal squamous cell carcinoma cell lines. By detecting proliferation, invasion and apoptosis of TE6 and TE14 cells transfected with miR-194 mimics or mimic control, miR-194 was found to inhibit proliferation and invasion and promote apoptosis of esophageal squamous cell carcinoma cells. miR-194 was further verified to regulate proliferation, apoptosis and invasion of esophageal squamous cell carcinoma cells by directly targeting KDM5B. Furthermore, animal studies were performed and showed that overexpression of miR-194 inhibited the growth of esophageal squamous cell carcinoma tumors in vivo. These results confirmed our speculation that miR-194 targets KDM5B to inhibit esophageal squamous cell carcinoma development and progression. These findings offer new clues for esophageal squamous cell carcinoma development and progression and novel potential therapeutic targets for esophageal squamous cell carcinoma.

Galectin-3 knockdown increases gefitinib sensitivity to the inhibition of EGFR endocytosis in gefitinib-insensitive esophageal squamous cancer cells.

Esophageal cancer (EC) is one of the most aggressive malignancies with a distinctly high incidence and mortality rate. Esophageal squamous cell carcinoma (ESCC) is the major histologic subtype of EC, with 40-70 % of tumors overexpressing the epidermal growth factor receptor (EGFR). Blockade of EGFR signal transduction may be a promising and effective strategy for EC therapy. However, the therapeutic efficacy of EGFR-tyrosine kinase inhibitors is clinically limited because of drug resistance. Galectin-3, a member of the animal lectin family, has been associated with a variety of biological functions and the progression of multiple tumors, including ESCC. In this study, we investigated the role of galectin-3 involved in potential gefitinib-resistance mechanisms in EGFR-positive ESCC cell lines. The results revealed that gefitinib treatment induced different inhibitory effects on cell viability, cell cycle progression and cell invasion in gefitinib-sensitive KYSE-450 and gefitinib-insensitive TE-8 cells with different levels of galectin-3 expression. Interestingly, we further found that EGF-induced EGFR endocytosis and EGFR signaling were different between gefitinib-sensitive and gefitinib-insensitive ESCC cell lines. Galectin-3 inhibition in combination with gefitinib treatment induced greater inhibitory effects on cell viability, cell cycle progression and cell invasion in gefitinib-insensitive TE-8 cells. Moreover, galectin-3 inhibition increased the gefitinib sensitivity of TE-8 cells in terms of EGFR endocytosis in vitro and anti-tumor effects in vivo. Taken together, galectin-3 knockdown increased gefitinib sensitivity through the inhibition of EGFR endocytosis in gefitinib-insensitive ESCC cells and galectin-3 may be a rational therapeutic target in ESCC with gefitinib resistance.

Acute toxicity, respiratory reaction, and sensitivity of three cyprinid fish species caused by exposure to four heavy metals.

Using 3 cyprinid fish species zebra fish, rare minnow, and juvenile grass carp, we conducted assays of lethal reaction and ventilatory response to analyze sensitivity of the fish to 4 heavy metals. Our results showed that the 96 h LC50 of Hg(2+) to zebra fish, juvenile grass carp, and rare minnow were 0.14 mg L(-1), 0.23 mg L(-1), and 0.10 mg L(-1), respectively; of Cu(2+)0.17 mg L(-1), 0.09 mg L(-1), and 0.12 mg L(-1) respectively; of Cd(2+)6.5 mg L(-1), 18.47 mg L(-1), 5.36 mg L(-1), respectively; and of Zn(2+)44.48 mg L(-1), 31.37 mg L(-1), and 12.74 mg L(-1), respectively. Under a 1-h exposure, the ventilatory response to the different heavy metals varied. Ventilatory frequency (Vf) and amplitude (Va) increased in zebra fish, juvenile grass carp, and rare minnows exposed to Hg(2+) and Cu(2+) (P<0.05), and the Vf and Va of the 3 species rose initially and then declined when exposed to Cd(2+). Zn(2+) had markedly different toxic effects than the other heavy metals, whose Vf and Va gradually decreased with increasing exposure concentration (P<0.05). The rare minnow was the most highly susceptible of the 3 fish species to the heavy metals, with threshold effect concentrations (TEC) of 0.019 mg L(-1), 0.046 mg L(-1), 2.142 mg L(-1), and 0.633 mg L(-1) for Hg(2+), Cu(2+), Cd(2+), and Zn(2+), respectively. Therefore, it is feasible to use ventilatory parameters as a biomarker for evaluating the pollution toxicity of metals and to recognize early warning signs by using rare minnows as a sensor.

Short-term impact of reservoir impoundment on the patterns of mercury distribution in a subtropical aquatic ecosystem, Wujiang River, southwest China.

Surveys on pre- and post-impoundment total mercury concentrations in water, seston and fish were conducted during 2007-2008 in the Wujiang River, southwest China. Compared with the pre-impoundment, total mercury in the reservoir and downstream water rapidly increased by 164-303 % during the first half year of flooding, and then decreased by 61.7-62.2 % after 9 months of flooding. However, total mercury in seston from the reservoir and downstream generally declined. There was no significant difference in the total mercury between reservoir fish with different habitat preference and feeding habit. We find that fish tissue mercury concentration significantly increased threefold after flooding, and the increasing rate is lower than those in subarctic and temperate reservoirs. The pre- and post-impoundment fish samples exceeding the Chinese hygienic standard for tolerances of mercury in foods increased from 1.3 to 17.4 %. Long-term monitoring of fish mercury level in Wujiang River should be undertaken to ensure local food security.