RGS16 regulates Hippo-YAP activity to promote esophageal cancer cell proliferation and migration.

Esophageal Squamous Cell Carcinoma (ESCC) is a common malignant tumor of digestive tract, accounting for 90% of all pathological types of esophageal cancer. Despite the rapid development of multi-disciplinary treatment such as surgery, chemotherapy, radiotherapy and chemoradiotherapy, the prognosis of patients with ESCC is still poor. Regulators of G-protein signaling (RGSs) are involved in the processes of various cancers. The expression levels of its family member RGS16 are abnormally elevated in a variety of tumors, but its role in ESCC is still unclear. We found that RGS16 expression is aberrantly increased in ESCC tissues and correlated with poor prognosis of ESCC patients from The Cancer Genome Atlas (TCGA) database and our collected ESCC tissues. Moreover, knockdown of RGS16 in two ESCC cells could indeed inhibit their proliferation and migration. We further explored the molecular mechanism of RGS16 in ESCC, and the correlation analysis from TCGA database showed that the mRNA levels of RGS16 was positively correlated with that of CTGF and CYR61, two target genes of Hippo-YAP signaling. Consistently, RGS16- knockdown significantly inhibited the expression of CTGF and CYR61 in ESCC cells. We found that the phosphorylation levels of LATS1 and YAP were significantly increased and YAP translocated into the cytoplasm after depletion of RGS16 in ESCC cells. Also, RGS16-knockdown promoted the interaction between LATS1 and upstream kinase MST1. In addition, reintroduction of a constitutive active YAP5A mutant significantly rescued CTGF expression and cell proliferation in RGS16-knockdown cells. Together, our work revealed that RGS16 promoted YAP activity through disrupting the interaction between LATS1 and MST1, thus promoting the proliferation and migration of ESCC cells.

How do different arsenic species affect the joint toxicity of perfluorooctanoic acid and arsenic to earthworm Eisenia fetida: A multi-biomarker approach.

Perfluorooctanoic acid (PFOA) and arsenic are widely distributed pollutants and can coexist in the environment. However, no study has been reported about the effects of different arsenic species on the joint toxicity of arsenic and PFOA to soil invertebrates. In this study, four arsenic species were selected, including arsenite (As(III)), arsenate (As(V)), monomethylarsonate (MMA), and dimethylarsinate (DMA). Earthworms Eisenia fetida were exposed to soils spiked with sublethal concentrations of PFOA, different arsenic species, and their binary mixtures for 56 days. The bioaccumulation and biotransformation of pollutants, as well as eight biomarkers in organisms, were assayed. The results indicated that the coexistence of PFOA and different arsenic species in soils could enhance the bioavailability of arsenic species while reducing the bioavailability of PFOA, and inhibit the arsenic biotransformation process in earthworms. Responses of most biomarkers in joint treatments of PFOA and As(III)/As(V) showed more significant variations compared with those in single treatments, indicating higher toxicity to the earthworms. The Integrated Biomarker Response (IBR) index was used to integrate the multi-biomarker responses, and the results also exhibited enhanced toxic effects in combined treatments of inorganic arsenic and PFOA. In comparison, both the biomarker variations and IBR values were lower in joint treatments of PFOA and MMA/DMA. Then the toxic interactions in the binary mixture systems were characterized by using a combined method of IBR and Effect Addition Index. The results revealed that the toxic interactions of the PFOA/arsenic mixture in earthworms depended on the different species of arsenic. The combined exposure of PFOA with inorganic arsenic led to a synergistic interaction, while that with organic arsenic resulted in an antagonistic response. Overall, this study provides new insights into the assessment of the joint toxicity of perfluoroalkyl substances and arsenic in soil ecosystems.

Contribution, Composition, and Structure of EPS by In Vivo Exposure to Elucidate the Mechanisms of Nanoparticle-Enhanced Bioremediation to Metals.

Bacterial extracellular polymeric substances (EPS) have been recently found to contribute most for metal removal in nanoenhanced bioremediation. However, the mechanism by which NPs affect EPS-metal interactions is not fully known. Here, Halomonas sp. was employed to explore the role of EPS after in vivo exposure to Cd/Pb and polyvinylpyrrolidone (PVP) coated iron oxide nanoparticles (IONPs, 20 mg L-1) for 72 h. Cd-IONPs produced the highest concentrations of EPS proteins (136.3 mg L-1), while Cd induced the most production of polysaccharides (241.0 mg L-1). IONPs increased protein/polysaccharides ratio from 0.2 (Cd) to 1.2 (Cd-IONPs). The increased protein favors the formation of protein coronas on IONPs surface, which would promote Cd adsorption during NP-metal-EPS interaction. FTIR analysis indicated that the coexistence of Cd and IONPs interacted with proteins more strongly than with polysaccharides. Glycosyl monomer analyses suggested mannose and glucose as target sugars for EPS complexation with metals, and IONPs reduced metal-induced changes in monosaccharide profiles. Protein secondary structures changed in all treatments, but we could not distinguish stresses induced by metals from those by IONPs. These findings provide greater understanding of the role of EPS in NP-metal-EPS interaction, providing a better underpinning knowledge for the application of NP-enhanced bioremediation.

Transferrin receptors/magnetic resonance dual-targeted nanoplatform for precise chemo-photodynamic synergistic cancer therapy.

Various drug delivery strategies to improve cancer therapeutic efficacy have been actively investigated. One major challenge is to improve the targeting ability. Here elaborately designed nanocarriers (NCs) named as Tf-5-ALA-PTX-NCs are demonstrated to address this problem. In this nanostructure, paclitaxel (PTX) and 5-aminolevulinic acid (5-ALA) were co-encapsulated within magnetic nanocarriers to achieve synergistic chemotherapy and photodynamic therapy, while transferrin (Tf) was conjugated with modified copolymer Pluronic P123 and embedded in the surface of the nanocarriers, which endows nanocarriers with Tf targeting and magnetic targeting to enhance the anti-tumor outcome. Results demonstrated that Tf-5-ALA-PTX-NCs significantly enhanced the targeting drug delivery to MCF-7 cells and synergistically induced apoptosis and death of MCF-7 cells in vitro and highly efficient tumor ablation in vivo. Intriguingly, Tf-5-ALA-PTX-NCs have a controllable "on/off" switch to enhance the drug release. The dual-targeted nanocarriers would be a promising versatile anti-tumor drug delivery and imaging-guided cancer chemo-photodynamic synchronization therapy strategy.

Preparation of a newly synthesized biopolymer binder and its application to reduce the erosion of tailings.

A new type of binder was developed by grafting casein and ß-glucan to investigate its effect on tailings erosion and plant growth. 6% casein and 2% ß-glucan were recommended as the best ratio of the new biopolymer binder, which had the best effect on the soil utilization of iron tailings. The infrared analysis of the new binder demonstrated that casein and ß-glucan reacted adequately as raw materials. The results of physichemical properties and loss prevention of iron tailings showed that the binder-treated soils demonstrated lower erodibility compared with untreated iron tailings. The particle size of the tailings was increased after the addition of the binder. In treated soil, the content of soil organic matter increased significantly, which provided sufficient nutrients for the plants growing. Compared with natural tailings without binder, plant height, fresh weight, chlorophyll content, and enzyme activity (POD and SOD) were also significantly increased. This study overcame the current defects of biopolymer in soil improvement and provided an environmentally friendly method to prevent the loss of iron tailings and promote its soil utilization efficiency.

Co-Removal Effect and Mechanism of Cr(VI) and Cd(II) by Biochar-Supported Sulfide-Modified Nanoscale Zero-Valent Iron in a Binary System.

This study aimed to explore the co-removal effect and mechanism of Cr(VI) and Cd(II) with an optimized synthetic material. The toxicity and accumulation characteristics of Cr(VI) and Cd(II) encountered in wastewater treatment areas present significant challenges. In this work, a rational assembly of sulfide-modified nanoscale zero-valent iron (SnZVI) was introduced into a biochar (BC), and a Cr(VI)-Cd(II) binary system adsorbent with high efficiency was synthesized. When the preparation temperature of the BC was 600 °C, the molar ratio of S/Fe was 0.3, the mass ratio of BC/SnZVI was 1, and the best adsorption capacities of BC-SnZVI for Cr(VI) and Cd(II) in the binary system were 58.87 mg/g and 32.55 mg/g, respectively. In addition, the adsorption mechanism of BC-SnZVI on the Cr(VI)-Cd(II) binary system was revealed in depth by co-removal experiments, indicating that the coexistence of Cd(II) could promote the removal of Cr(VI) by 9.20%, while the coexistence of Cr(VI) could inhibit the removal of Cd(II) by 43.47%. This work provides a new pathway for the adsorption of Cr(VI) and Cd(II) in binary systems, suggesting that BC-SnZVI shows great potential for the co-removal of Cr(VI) and Cd(II) in wastewater.

Biosorption capacity of Mucor circinelloides bioaugmented with Solanum nigrum L. for the cleanup of lead, cadmium and arsenic.

The biosorption and bioaugmentation performances of Mucor circinelloides were investigated under different contact time, initial metal(loid) concentration and species. The microbe-plant interaction appeared synergistic with enhancing plant growth and alleviating oxidative damages induced by lead, cadmium and arsenic. The bioaugmentation with M. circinelloides led to significant immobilization on lead, cadmium and arsenic as indicated by the decreases of metal(loid) transfer and bioavailability in plant-microbe aqueous system. Lead, cadmium and arsenic were mainly allocated on cell wall and a few parts entered into intercellular system, suggesting cell wall adsorption and intracellular bioaccumulation served as the main mechanisms of M. circinelloides. The adsorption kinetics and isotherms on lead, cadmium and arsenic were fitted well with the pseudo-second-order and Langmuir models, with the maximum adsorption capacities of 500, 15.4 and 29.4 mg·g-1 fungal biomass at pH 6.0 and 25 â„ƒ. The optimum initial concentration and contact time were 300-10-20 mg·L-1 and 2 h. This study provides a basis for M. circinelloides as a promising adsorbent and bioaugmented agent for the cleanup of soil/aqueous environment contaminated with lead, cadmium and arsenic.

Effects of functional carbon nanodots on water hyacinth response to Cd/Pb stress: Implication for phytoremediation.

Phytoremediation is one of the effective, economic and green approaches to cope with the increasing worldwide heavy metal (HM) pollution. Here, we evaluate the effects of functional carbon nanodots (FCNs) against the hyperaccumulation capacity as well as the physiological and genetic responses of water hyacinth under Pb2+ or/and Cd2+ stress. The bioaccumulation efficiency, HM content and transfer factor, biomass, root development, chlorophyll content, antioxidant system and genes expression are investigated at various concentration of HMs. Based on the excellent adsorption capacity and plant growth regulation ability, FCNs and nitrogen doped FCNs (N-FCNs) cooperate with water hyacinth to improve their HMs removal efficiencies. FCNs and N-FCNs immobilize excess HMs ions in plant, smartly regulate enzymatic levels to mitigate oxidative damage, as well as regulate the microelement uptake and related gene expression, thus improve plant tolerance against HMs stress. Although Pb and Cd have antagonistic effects on bioaccumulation of water hyacinth to the single metal, FCNs and N-FCNs can cooperate with water hyacinth to raise the removal efficiency of HMs in water, and enhance plant tolerance under Pb-Cd combined stress. The promotion effects of FCNs and N-FCNs on phytoremediation are more effective than conventional carbon nanomaterials, including carbon nanotubes and graphene oxides. These findings demonstrate that the application of FCNs or N-FCNs can improve the phytoremediation efficiency in the restoration of HMs contaminated water area. This study provides important insights into the possibility of using FCNs-based nanomaterials and water hyacinth as synergistic system for remediation of Cd-Pb contaminated water area.

Distribution Characteristics and Risk Assessment of Polycyclic Aromatic Hydrocarbons in Soils of a Steel Enterprise in East China.

To meet the goal of sustainable development, many large steel enterprises in China have been relocated, leaving serious polycyclic aromatic hydrocarbon (PAH) pollution problems at the abandoned sites. In this study, the spatial distribution and potential health risks of PAHs in soils of a large steel enterprise in East China were studied. The total concentrations of 16 PAHs ranged from 93.96 to2.61E + 05 µg/kg. A total of 54.84% of the samples reached the level of severe pollution, with coking plants and iron works showing much more serious problems than other areas. The contribution levels of PAHs with high molecular weights were high, especially those of 4-ring PAHs. The toxic equivalent concentrations exceeded the values recommended by the Canadian guide. The average carcinogenic risk value of the whole region was greater than 10-6, indicating high carcinogenic risk. The above assessment indicates that the area must be remediated before further development occurs.

Mass spectrometry analysis reveals aberrant N-glycans in colorectal cancer tissues.

Aberrant glycosylation is strongly correlated with the development of various cancers. Tumor-associated carbohydrate antigens, including N-glycans, are predominantly expressed on the tumor cell surface. Because the incidence of colorectal cancer is high in China, we investigated aberrant N-glycans from colorectal cancer tissues (CRC) in Chinese patients. By Linear ion trap quadrupole-electrospray ionization mass spectrometry, we performed glycomic assays on N-glycans obtained from solid CRC tissues and paired peritumoral tissues. In total, aberrant N-glycans were expressed in the colorectal tumor tissues. Specifically, seven bisecting structures (M/Z 9732+, 10602+, 10752+, 11622+, 11772+, 12642+, 13522+) decreased, M/Z 10552+ (two-antennae complex N-glycan) and M/Z 12792+ (three-antennae complex N-glycan) decreased, M/Z 10132+ and M/Z 11162+ (high-mannose N-glycan) increased, and M/Z 12282+ (bifucosylated N-glycan) increased. To evaluate the MS profile data, several statistical tools were applied, including student's t test, orthogonal partial least squares discriminant analysis and receiver operating characteristic curve. The measurement of the degree of bisecting N-glycans had an area under the curve value of 0.823. Interestingly, we observed that the bisecting N-glycans decreased with the tumor stages. This phenomenon was not found in esophageal squamous cell carcinoma, in which the bisecting N-glycans had no change. Thus, the expression of bisecting N-glycans may be an interesting point in the study of colorectal cancer.

Circ-TTC17 Promotes Proliferation and Migration of Esophageal Squamous Cell Carcinoma.

BACKGROUND: Circular RNAs (circRNAs), a special class of noncoding RNAs with the characteristic of covalent closed-loop structure, have been widely found in various organisms. Growing evidence has shown that circRNAs play a crucial role in regulating biological functions of cancers. However, the specific role of circRNAs in esophageal squamous cell carcinoma (ESCC) remains largely unknown. AIM: The present study aims to investigate the effects of circ-TTC17 in ESCC clinical samples as well as cells. METHODS: Sanger sequencing and agarose gel electrophoresis were used to verify the specificity of circ-TTC17. Expression levels of circ-TTC17 in ESCC cells, plasma, and tissues were measured by quantitative real-time polymerase chain reaction. A colony formation experiment, CCK-8 assay, and wound-healing assay were applied to detect the functions of circ-TTC17 in KYSE30 and KYSE450 cells. A nucleus-cytoplasm fractionation experiment was used to probe the location of circ-TTC17 in ESCC cells. Finally, a network of circ-TTC17 with its targeted miRNAs interactions and corresponding mRNAs was analyzed and framed by bioinformatics. RESULTS: The expression level of circ-TTC17 was found to be significantly higher in ESCC cells, plasma, and tissues compared with normal cases. In vitro experiments indicated that circ-TTC17 promoted proliferation and migration of ESCC cells. Bioinformatics predictions showed that circ-TTC17 might regulate progress of ESCC by acting as a sponge for microRNAs (miRNAs). CONCLUSIONS: The results of this study demonstrate that upregulated circ-TTC17 plays a key role in promoting proliferation and migration of ESCC cells and has potential to become a novel biomarker for diagnosis, treatment, and prognosis of ESCC in the future.

Toxic responses of cytochrome P450 sub-enzyme activities to heavy metals exposure in soil and correlation with their bioaccumulation in Eisenia fetida.

The dose- and time- dependent responses of cytochrome P450 (CYP) sub-enzyme activities to heavy metals in soil, and the relationships between biomarker responses and metal bioaccumulation in Eisenia fetida were evaluated. Earthworms were exposed to soils spiked with increasing doses of Cd, Cu, Pb or Zn for 21 d. Results demonstrated that EROD and CYP3A4 activities responded significantly with increasing dose and exposure duration. EROD activity significantly (P < 0.05) correlated with CYP3A4 activity exposed to Pb and Cu. The earthworm metal burdens had significant correlation with the total metal concentrations in soil (P < 0.01). The bioaccumulation factor (BAF) decreased with the increasing metal concentration in soil. The order of metal bioavailability to E. fetida was Cd > Zn > Cu > Pb. CYP3A4 activity in Pb-exposed earthworms had a significant correlation with the accumulated metal (P < 0.05). Both EROD and CYP3A4 activities in Cu-exposed worms negatively correlated with BAF (P < 0.05). Based on Discriminant Analysis (DA), CYPs activities were sensitive biomarkers of heavy metals exposure, and we also concluded that different biomarkers with multiple durations could be conducted in the eco-toxicological diagnosis of soil pollution.

Identification of the long non-coding RNA POU3F3 in plasma as a novel biomarker for diagnosis of esophageal squamous cell carcinoma.

BACKGROUND: Recent studies have demonstrated that long non-coding RNAs (lncRNAs) were present in the blood of cancer patients and have shown great potential as powerful and non-invasive tumor markers. However, little is known about the value of lncRNAs in the diagnosis of esophageal squamous cell carcinoma (ESCC). We hypothesized that ESCC-related lncRNAs might be released into the circulation during tumor initiation and could be utilized to detect and monitor ESCC. METHODS: Ten lncRNAs (HOTAIR, AFAP1-AS1, POU3F3, HNF1A-AS1, 91H, PlncRNA1, SPRY4-IT1, ENST00000435885.1, XLOC_013104 and ENST00000547963.1) which previously found to be differently expressed in esophageal cancer were selected as candidate targets for subsequent circulating lncRNA assay. A four-stage exploratory study was conducted to test the hypothesis: (1) optimization of detected method to accurately and reproducibly measure ESCC-related lncRNAs in plasma and serum; (2) evaluation of the stability of circulating lncRNAs in human plasma or serum; (3) exploration the origin of ESCC-related lncRNAs in vitro and in vivo; (4) evaluation the diagnostic power of circulating lncRNAs for ESCC. RESULTS: ESCC-related lncRNAs were detectable and stable in plasma of cancer patients, and derived largely from ESCC tumor cells. Furthermore, plasma levels of POU3F3, HNF1A-AS1 and SPRY4-IT1 were significantly higher in ESCC patients compared with normal controls. By receiver operating characteristic curve (ROC) analysis, among the three lncRNAs investigated, plasma POU3F3 provided the highest diagnostic performance for detection of ESCC (the area under the ROC curve (AUC), 0.842; p < 0.001; sensitivity, 72.8%; specificity, 89.4%). Moreover, use of POU3F3 and SCCA in combination could provide a more effective diagnosis performance (AUC, 0.926, p < 0.001, sensitivity, 85.7%; specificity, 81.4%). Most importantly, this combination was effective to detect ESCC at an early stage (80.8%). CONCLUSIONS: Plasma POU3F3 could serve as a potential biomarker for diagnosis of ESCC, and the combination of POU3F3 and SCCA was more efficient for ESCC detection, in particular for early tumor screening.

Upregulation of the long noncoding RNA PCAT-1 correlates with advanced clinical stage and poor prognosis in esophageal squamous carcinoma.

Recent studies reveal that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. Prostate cancer-associated ncRNA transcript 1 (PCAT-1) is one of the lncRNAs involved in cell apoptosis and proliferation of prostate cancer. This study aimed to assess the potential role of PCAT-1 specifically in the pathogenesis of esophageal squamous cell carcinoma (ESCC). Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PCAT-1 in matched cancerous tissues and adjacent noncancerous tissues from 130 patients with ESCC, 34 patients with non-small cell lung cancer (NSCLC), and 30 patients with gastric carcinoma (GC). The correlation of PCAT-1 with clinicopathological features and prognosis were also analyzed. The expression of PCAT-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (70.8%, p < 0.01), and the high level of PCAT-1 expression was significantly correlated with invasion of the tumor (p = 0.024), advanced clinical stage (p = 0.003), lymph node metastasis (p = 0.032), and poor prognosis. However, PCAT-1 mRNA expression had no significant difference between paired primary cancerous tissues and the adjacent noncancerous tissues in 34 cases of NSCLC (p = 0.293) and 30 cases of GC (p = 0.125). High expression of PCAT-1 was specifically correlated with invasion of cancer tissues, metastasis of lymph node, and advanced tumor stage of ESCC. High expression of PCAT-1 might reflect poor prognosis of ESCC and indicate a potential diagnostic target in ESCC patients. Adjuvant therapy targeting PCAT-1 molecule might be effective in treatment of ESCC.

Association of decreased expression of long non-coding RNA LOC285194 with chemoradiotherapy resistance and poor prognosis in esophageal squamous cell carcinoma.

BACKGROUND: Expression of the long non-coding RNA (lncRNA) LOC285194 was previously shown to be correlated with aggressive clinicopathological features and poor prognosis in several cancers. The aim of the present study was to explore the relationship between LOC285194 expression and clinical outcomes in esophageal squamous cell carcinoma (ESCC), so as to assess whether it could be a novel biomarker for prognosis and prediction of response to therapy on ESCC patients. METHODS: The method of quantitative real-time polymerase chain reaction (qRT-PCR) was used to measure LOC285194 expression in pretreatment biopsy specimens and matched normal tissue derived from ESCC patients who underwent preoperative chemoradiotherapy followed by surgical resection (CRT + S group; n = 55) or from those who received surgical resection alone (S group; n = 87). The association between LOC285194 expression and clinicopathological features and prognosis were then analyzed. RESULTS: LOC285194 expression was significantly down-regulated in ESCC tumor tissues when compared with the adjacent normal tissues (p < 0.001). Low expression of LOC285194 was associated with larger tumor size (p = 0.002), advanced TNM stage (p = 0.018), more lymph node metastases (p = 0.013) and distant metastases (p = 0.015). In the CRT + S group, the pathological complete response rate was 57% (16/28) for the LOC285194-high group, and 15% (4/27) for the LOC285194-low group. Univariate analysis revealed that low expression of LOC285194 was significantly correlated with CRT response (p = 0.002). Moreover, Kaplan-Meier survival analysis revealed that patients with low expression of LOC285194 had a decreased disease free survival (DFS) (p < 0.001) and overall survival (OS) (p < 0.001). Multivariable analysis further identified low expression of LOC285194 as an independent prognosis factor for CRT response (p = 0.011), DFS (p < 0.001) and OS (p = 0.002). CONCLUSION: Decreased expression of LOC285194 could serve as a molecular marker to predict the clinical outcome of ESCC patients after surgery, and select patients who would benefit from preoperative CRT.

Long noncoding RNA SPRY4-IT1 is upregulated in esophageal squamous cell carcinoma and associated with poor prognosis.

LncRNA SPRY4-IT1 has been shown to promote the progression of melanoma. However, the role of lncRNA SPRY4-IT1 in human esophageal squamous cell carcinoma (ESCC) remains unclear. The purpose of this study is to investigate the clinical significance and biological functions of SPRY4-IT1 in ESCC. The expression levels of lncRNA SPRY4-IT in 92 ESCC patients and 8 ESCC cell lines were evaluated by quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). The prognostic significance was evaluated using Kaplan-Meier and Cox regression analyses. Small interfering RNA (siRNA) was used to suppress SPRY4-IT1 expression in ESCC cell lines. Both in vitro and in vivo assays were performed to further explore its role in tumor progression. SPRY4-IT1 levels were significantly higher in ESCC tissues and cells than in corresponding adjacent noncancerous tissues and nontumorigenic esophageal epithelial cells, and the ESCC patients with higher SPRY4-IT1 expression had an advanced clinical stage and poorer prognosis than those with lower SPRY4-IT1 expression. The multivariate analysis revealed that SPRY4-IT1 expression level is an independent prognostic factor in ESCC patients. In vitro assays demonstrated that knockdown of SPRY4-IT1 reduced cell proliferation, invasiveness, and migration. In vivo assays demonstrated that knockdown of SPRY4-IT1 decreases cell growth. SPRY4-IT1 is a novel molecule involved in ESCC progression, which may provide a potential prognostic biomarker and a potential target for therapeutic intervention.

Upregulation of the long non-coding RNA PlncRNA-1 promotes esophageal squamous carcinoma cell proliferation and correlates with advanced clinical stage.

BACKGROUND: Recent studies revealed that long noncoding RNAs (lncRNAs) play critical regulatory roles in cancer biology. PlncRNA-1 is one of lncRNAs that is associated with cell apoptosis and proliferation of prostate cancer. AIM: This study aimed to assess the potential role of PlncRNA-1 in the pathogenesis of esophageal squamous cell carcinoma (ESCC). MATERIALS AND METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the expression level of PlncRNA-1 in 73 pairs of ESCC and their matched normal tissues. The correlation of PlncRNA-1 with clinicopathological features and clinical stages was also analyzed. Cancer cell proliferation and apoptosis were assessed following knock-down of PlncRNA-1 by MTT, colony formation assay, and flow cytometry. RESULTS: The expression of PlncRNA-1 was significantly higher in human ESCC compared with the adjacent noncancerous tissues (69.8 %, p < 0.05), and the high level of PlncRNA-1 expression was significantly correlated with advanced clinical stage (p < 0.01) and lymph node metastasis (p < 0.05). Furthermore, knockdown of PlncRNA-1 reduced cell proliferation and increased the apoptosis in vitro. CONCLUSIONS: PlncRNA-1 plays an important role in ESCC cell proliferation. Overexpression of PlncRNA-1 is correlated with advanced tumor stage and lymph node metastasis, and may serve as a potential prognostic marker and therapeutic target for ESCC.

Licochalcone-A sensitizes human esophageal carcinoma cells to TRAIL-mediated apoptosis by proteasomal degradation of XIAP.

BACKGROUND/AIMS: Esophageal carcinoma is one of the most aggressive human cancers, and novel treatment modality is required. Although expressing adequate levels of functional tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors DR4/DR5, significant proportion of esophageal cancer cells exhibit resistance to the cytotoxic effect of this ligand. Licochalcone-A (LA), a flavonoid present in a variety of edible plants, exhibits a wide spectrum of pharmacologic properties such as anticancer, antioxidant, and anti-inflammatory activities. METHODOLOGY: Eca109 and TE1 cells were cultured and transfected, then their viability was detected using MTT assay. Immunoprecipitation and immunoblotting analysis and RT-PCR analysis were also performed. RESULTS: In this study, we found that LA synergistically caused the TRAIL-induced apoptosis in Eca109 and TE1 cells. Such potentiation was achieved through inhibiting Akt activation and promoting proteasomal degradation of X-linked Inhibitor of Apoptosis Protein (XIAP) which mediated the survival signals and allow the cells to escape from apoptosis in various human cancers. CONCLUSIONS: The combination of TRAIL and LA might be a novel therapeutic strategy for esophageal carcinoma patients who fail to respond to standard chemotherapy.

Upregulation of the long non-coding RNA HOTAIR promotes esophageal squamous cell carcinoma metastasis and poor prognosis.

Recent studies of the individual functionalities of long non-coding RNAs (lncRNAs) in the development and progression of cancer have suggested that HOX transcript antisense RNA (HOTAIR) is capable of reprogramming chromatin organization and promoting cancer cell metastasis. In order to ascertain the expression pattern of the lncRNA HOTAIR and assess its biological role in the development and progression of esophageal squamous cell carcinoma (ESCC), HOTAIR expression in ESCC tissues and adjacent noncancerous tissues were collected from 78 patients and measured by real-time reverse transcription-polymerase chain reaction (RT-PCR). HOTAIR correlation with clinicopathological features and prognosis was also analyzed. Suppression of HOTAIR using siRNA treatment was performed in order to explore its role in tumor progression. Notably elevated HOTAIR expression levels were observed in cancerous tissues compared to adjacent noncancerous tissues (96%, P < 0.01), showing a high correlation with cancer metastasis (P < 0.01), elevated TNM (2009) stage classification (P < 0.01), and lowered overall survival rates (P = 0.003). Multivariate analysis revealed that HOTAIR expression (P = 0.003) is also an independent prognostic factor for comparison of TNM stage (P = 0.024) and lymph node metastasis (P = 0.010). Furthermore, in vitro assays of the ESCC cell line KYSE30 demonstrated that knockdown of HOTAIR reduced cell invasiveness and migration while increasing the response of cells to apoptosis. Thus, HOTAIR is a novel molecule involved in both ESCC progression and prognosis. Full elucidation of HOTAIR functionality relevant to ESCC may open avenues for the use of lncRNAs in identification of novel drug targets and therapies for ESCC and other prevalent cancers.

Ecological toxicity of Cd, Pb, Zn, Hg and regulation mechanism in Solanum nigrum L.

This study aimed to investigate the combined ecotoxicological effects of Cd, Pb, Zn, Hg and regulation mechanisms in Solanum nigrum L. In this work, the co-exposure of these four heavy metals hindered the transformation of Cd, Zn, and Hg (except Pb) from available to non-available chemical forms. Individual Cd, Pb, Zn and Hg induced the oxidative damages to S. nigrum L., while their combination further enhanced this ecological toxicity. By internal regulation, the ecological toxicity of metals to S. nigrum L. could be alleviated to a certain extent. Specifically, S. nigrum L. was a hyperaccumulator of Cd with BCF ＞1. Moreover, since BCFroot of Pb, Zn and Hg were all greater than BCFshoot, S. nigrum L. could accumulate Pb, Hg and Zn mainly in plant roots, which was beneficial for the detoxification of plants. Meanwhile, the immobilization by cell wall (the proportions of Cd, Pb, Zn and Hg in the cell wall were 54.46-84.92%, 38.33-49.25%, 48.38-56.19% and 45.97-63.47% in low metal concentration treatments) and the sequestration in vacuole (the proportions of Cd, Pb, Zn, and Hg in the soluble fractions are 50.99-59.00%, 41.05-45.46%, 37.54-61.04% and 33.47-61.35% in high metal concentration treatments) also act as important detoxification pathways. The external regulation was mainly the changes of soil microbial communities influenced by plants. Specifically, the richness and diversity of bacteria in rhizosphere soil were increased, and roots of S. nigrum L. recruited some potentially beneficial microbials. This study provided a theoretical basis and guidance for S. nigrum L. as a phytoremediation plant under combined heavy metal pollution.