Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC. A number of known onco-lncRNA and many putative novel ones were effectively identified by URW-LPE. Importantly, we identified lncRNA625 as a novel regulator of ESCC cell proliferation, invasion and migration. ESCC patients with high lncRNA625 expression had significantly shorter survival time than those with low expression. LncRNA625 also showed specific prognostic value for patients with metastatic ESCC. Finally, we identified E1A-binding protein p300 (EP300) as a downstream executor of lncRNA625-induced transcriptional responses. These findings establish a catalog of novel cancer-associated functional lncRNAs, which will promote our understanding of lncRNA-mediated regulation in this malignancy.
Ambient air samples were collected at two different locations between 2011 and 2012 in Zhengzhou, China in order to assess the concentration level, health risks, as well as the sources of polycyclic aromatic hydrocarbons (PAHs) in particulate matter (PM2.5). The mean annual levels of PM2.5 observed at industry site and residential site were 172 ± 121 and 160 ± 72 μg m(-3), respectively, which were about five times the annual value of proposed PM2.5 standard (35 μg m(-3)) in China. The PM2.5 in all daily samples (n = 47) exceeds the proposed PM2.5 standard in China (75 μg m(-3)) at both industrial and residential sites. Seasonal variations of PM2.5 showed a clear trend of winter > autumn > spring > summer at both sites. The total concentrations of 16 PM2.5-associated PAHs ranged from 61 ± 51 to 431 ± 281 and 38 ± 25 to 254 ± 189 ng m(-3), with mean value of 176 ± 233 and 111 ± 146 ng m(-3) at industry and residential sites, respectively. The major species were fluoranthene, pyrene, chrysene, benzo[b]fluoranthene and benzo[k]fluoranthene, and the concentration levels of PAHs in PM2.5 were higher in winter than those of other seasons at both sites. The annual mean values of toxicity equivalency concentrations of ∑16PAHs in PM2.5 were 22.8 and 13.5 ng m(-3) in industry and residential area, respectively. In this study, the risk level of adult citizens through inhalation exposure to PAHs was calculated. The average estimates of lifetime inhalation cancer risks were approximately 8.9 × 10(-7) and 6.3 × 10(-7) for industry and residential sites, respectively. The main sources of 16 PAHs from both diagnostic ratios and principle component analysis identified as vehicular emissions and coal combustion.
Background T. spiralis aspartic protease has been identified in excretion/secretion (ES) proteins, but its roles in larval invasion are unclear. The aim of this study was to characterize T. spiralis aspartic protease-2 (TsASP2) and assess its roles in T. spiralis invasion into intestinal epithelial cells (IECs) using RNAi. Methodology/Principal findings Recombinant TsASP2 (rTsASP2) was expressed and purified. The native TsASP2 of 43 kDa was recognized by anti-rTsASP2 serum in all worm stages except newborn larvae (NBL), and qPCR indicated that TsASP2 transcription was highest at the stage of intestinal infective larvae (IIL). IFA results confirmed that TsASP2 was located in the hindgut, midgut and muscle cells of muscle larvae (ML) and IIL and intrauterine embryos of the female adult worm (AW), but not in NBL. rTsASP2 cleaved several host proteins (human hemoglobin (Hb), mouse Hb, collagen and IgM). The proteolytic activity of rTsASP2 was host-specific, as it hydrolyzed mouse Hb more efficiently than human Hb. The enzymatic activity of rTsASP2 was significantly inhibited by pepstatin A. The expression levels of TsASP2 mRNA and protein were significantly suppressed by RNAi with 5 μM TsASP2-specific siRNA. Native aspartic protease activity in ML crude proteins was reduced to 54.82% after transfection with siRNA. Larval invasion of IECs was promoted by rTsASP2 and inhibited by anti-rTsASP2 serum and siRNA. Furthermore, cell monolayer damage due to larval invasion was obviously alleviated when siRNA-treated larvae were used. The adult worm burden, length of adult worms and female fecundity were clearly reduced in mice challenged using siRNA-treated ML relative to the PBS group, Conclusions rTsASP2 possesses the enzymatic activity of native aspartic protease and facilitates T. spiralis invasion of host IECs.
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