Correlation of MIF-AS1 polymorphisms with the risk and prognosis of gastric cancer.

BACKGROUND: The most studied genetic polymorphisms associated with gastric cancer (GC) risk are located in protein-coding genes. However, the localization of these in long non-coding RNAs (lncRNAs) has not been fully studied. We aim to investigate the associations of Long non-coding RNA macrophage migration inhibitory factor antisense RNA1(Lnc-MIF-AS1) five polymorphisms (rs755622, rs17004044, rs2070767, rs1007889, rs2000468) with the risk and prognosis of GC. METHODS: A total of 844 GC patients and 871 controls were included in the study. Genotyping was carried out using polymerase chain reaction-ligase detection reaction (PCR-LDR) technology. Odds ratios (ORs) and 95% confidence intervals (CIs) generated from unconditional logistic regression, were applied to quantify the effects of MIF-AS1 gene SNPs on GC risk. Log-rank test and Cox regression analysis were fitted to estimate hazard ratios (HRs) to quantify the effects of MIF-AS1 gene SNPs on GC prognosis. RESULTS: Significant associations were identified between MIF-AS1 rs17004044 variants and GC group in the codominant, dominant and additive models (OR = 2.843, P = 0.010; OR = 1.370, P = 0.004; and OR = 1.386; P = 0.001). In addition, association between rs17004044 variants and survival of GC was extremely observed (TC HR = 2.02 (1.21-3.37) P = 0.007, CC HR = 5.61 (2.12-14.83), P = 0.001). CONCLUSION: MIF-AS1 polymorphism rs17004044 contributes to increased predisposition and prognosis to GC.

Long noncoding RNA FAM225A promotes the malignant progression of gastric cancer through the miR-326/PADI2 axis.

Gastric cancer (GC) is a global health problem and further studies of its molecular mechanisms are needed to identify effective therapeutic targets. Although some long noncoding RNAs (lncRNAs) have been found to be involved in the progression of GC, the molecular mechanisms of many GC-related lncRNAs remain unclear. In this study, a series of in vivo and in vitro assays were performed to study the relationship between FAM225A and GC, which showed that FAM225A levels were correlated with poor prognosis in GC. Higher FAM225A expression tended to be correlated with a more profound lymphatic metastasis rate, larger tumor size, and more advanced tumor stage. FAM225A also promoted gastric cell proliferation, invasion, and migration. Further mechanistic investigation showed that FAM225A acted as a miR-326 sponge to upregulate its direct target PADI2 in GC. Overall, our findings indicated that FAM225A promoted GC development and progression via a competitive endogenous RNA network of FAM225A/miR-326/PADI2 in GC, providing insight into possible therapeutic targets and prognosis of GC.

RNF144A-AS1, a TGF-ß1- and hypoxia-inducible gene that promotes tumor metastasis and proliferation via targeting the miR-30c-2-3p/LOX axis in gastric cancer.

BACKGROUND: Although recent molecular analyses have improved our knowledge regarding gastric cancer (GC) biology, the molecular mechanisms that confer metastatic potential to GC remain poorly understood. In this study, we intend to explore the function and characterize the underlying mechanism of long noncoding RNA RNF144A-AS1 in GC metastasis and outgrowth. METHODS: The expression of RNF144A-AS1, miR-30c-2-3p, and Lysyl oxidase (LOX) was detected by quantitative real-time PCR assay. Fluorescence in situ hybridization and subcellular fractionation assay determined the cellular localization of RNF144A-AS1. Cell counting kit 8 assay, transwell assay, and tube formation assay were performed to detect the effect on cell proliferation, migration, invasion, and angiogenesis, respectively. Animal models were also applied to verify the effect on tumor metastasis, outgrowth, and angiogenesis. Bioinformatic analysis, luciferase reporter assay, and RNA immunoprecipitation (RIP) assay explored the interactions among RNF144A-AS1, miR-30c-2-3p, and LOX. Gene regulation was further validated by knockdown of Dicer or mutating the miRNA binding sites on RNF144A-AS1 and LOX 3'UTR. Cells were treated with recombinant human TGF-ß1 (Transforming Growth Factor ß1) to explore the effect of TGF-ß1 on RNF144A-AS1. Western blot and immunohistochemistry were used to detect protein expression. RESULTS: The expression of RNF144A-AS1 was significantly upregulated in GC tissues and was associated with poor prognosis and later-stage diseases. Hypoxia stimulated the expression of RNF144A-AS1 in a HIF-1α-independent manner. Additionally, RNF144A-AS1 was also induced by TGF-ß1. Loss and gain of function assays revealed that RNF144A-AS1 promoted tumor metastasis, angiogenesis, and proliferation. Mechanism exploration indicated RNF144A-AS1 served as a microRNA decoy of miR-30c-2-3p to release LOX. Gene Set Enrichment Analysis further suggested LOX and RNF144A-AS1 were enriched in the same gene sets, emphasizing the internal mechanism connection between these two genes. CONCLUSIONS: TGF-ß1- and hypoxia-inducible RNF144A-AS1 promoted tumor metastasis, angiogenesis, and proliferation through targeting the miR-30c-2-3p/LOX axis in GC, highlighting the value of the RNF144A-AS1/miR-30c-2-3p/LOX axis in therapeutic interventions of GC.

Five circRNAs Serve as Potential Diagnostic and Prognostic Biomarkers in Lung Adenocarcinoma.

BACKGROUND: The mortality rate of lung adenocarcinoma ranks first worldwide, higher than gastric, colorectal, breast, and other cancers. The lack of effective and accurate diagnosis contributes to the patient's unfavorable prognosis with lung adenocarcinoma since most patients are diagnosed at a late stage. In the present study, we aimed to investigate five circRNAs correlated with lung adenocarcinoma and their clinical roles. METHODS: We collected 68 unpaired serum and tissue samples from patients with lung adenocarcinoma and healthy volunteers. At the next stage, quantitative real-time polymerase chain reaction (qRT-PCR) assays were conducted. Furthermore, we uncovered the correlation of their expressions with clinicopathological features and the diagnostic values. Finally, the 5-year survival rate and disease-free rate were analyzed using Kaplan-Meier methods. RESULTS: The results revealed that expression levels of hsa_circ_001010, hsa_circ-ZNF609 were significantly elevated while hsa_circ-CRIMI1, hsa_circ-EPB41L2, and hsa_circ_0072309 were lower in lung adenocarcinoma serum samples and tissues than those in healthy controls (p < 0.05). Meanwhile, hsa_circ_001010 and hsa_circ-ZNF609 were downregulated hsa_circ-CRIMI1, hsa_circ-EPB41L2, and hsa_circ_0072309 were elevated in A549 cells compared with BEAS-2B cells. Knockdown of hsa_circ-CRIMI1, hsa_circ-EPB41L2, or hsa_circ_0072309 and overexpressing of hsa_circ_001010 and hsa_circ-ZNF609 could promote A549 cell apoptosis but inhibits proliferation as well. Furthermore, receiver operating characteristic (ROC) assays demonstrated that the area under the curve (AUC) were as follows: hsa_circ_001010 (0.8512, 95% CI, 0.7872 - 0.9152; p < 0.0001), hsa_circ-ZNF609 (0.7876, 95% CI, 0.7101 - 0.8651; p < 0.0001), hsa_circ-CRIMI1 (0.6614, 95% CI, 0.5708 - 0.7521; p < 0.0001), hsa_circ-EPB41L2 (0.6851, 95% CI, 0.5960 - 0.7742; p = 0.0002), and hsa_circ_0072309 (0.7359, 95% CI, 0.6250 - 0.8199; p < 0.0001). Notably, higher expressions of hsa_circ_001010, hsa_circ-ZNF609, and lower expressions of hsa_circ-CRIMI1, hsa_circ-BGT2, hsa_circ-EPB41L2, and hsa_circ_0072309 were positively correlated with clin-ical stage, lymph node metastasis, and smoking. Last but not least, patients with higher expressions of hsa_ circ_001010, hsa_circ-ZNF609, and lower expressions of hsa_circ-CRIMI1, hsa_circ-EPB41L2, and hsa_circ_ 0072309 had significantly lower overall survival rates and disease-free rates as well. CONCLUSIONS: We concluded that the five circRNAs might have diagnostic and prognosis significance in lung ade-nocarcinoma. However, further functional studies are warranted to ascertain the biological mechanisms of these circRNAs in the occurrence and development of lung adenocarcinoma.

Genetic polymorphisms of Cathepsin B are associated with gastric cancer risk and prognosis in a Chinese population.

BACKGROUND: Genetic polymorphisms are believed to represent a key aspect of predisposition to gastric cancer (GC). Therefore, considering the important role of Cathepsin B (CTSB) in promoting cancer onset and development, it could be very worthful to explore the function of CTSB-related genetic polymorphisms in GC. OBJECTIVE: In this study, we investigated the correlation of CTSB-related polymorphisms (rs9009A>T, rs6731T>C, rs1293303G>C, rs1874547C>T, rs3779659C>T, rs17814426C>T and rs148669985C>T) with GC risk and prognosis in a case-control study of 994 cases and 1000 controls. METHODS: All tag single nucleotide polymorphisms (SNPs) were genotyped by polymerase chain reaction-ligase detection reaction (PCR-LDR) sequencing technology. RESULTS: The results indicated rs9009, rs6731 and rs17814426 correlated with decreased risks of GC (HR = 0.97, p< 0.001; HR = 0.86, P= 0.019; HR = 0.85, P= 0.017; respectively). Stratification analysis further showed rs17814426 variant genotypes correlated with earlier T stage (p= 0.044). In addition, GC patients carrying the C allele of rs6371 had better overall prognosis (HR = 0.62, 95%CI = 0.44-0.88). CONCLUSION: Our results firstly suggested the importance of CTSB-related polymorphisms on GC which could predict GC risk and prognosis.

MicroRNA-653-5p Promotes Gastric Cancer Proliferation and Metastasis by Targeting the SOCS6-STAT3 Pathway.

MicroRNAs (miRNAs) are emerging as significant regulators of the tumorigenesis of gastric cancer (GC), and may be effective biomarkers for diagnosis, prognosis, and therapeutic targeting for GC. In this study, miR-653-5p was found to be significantly upregulated in GC tissues, serum, and cell lines and was strongly associated with poor prognosis in patients with GC. Furthermore, miR-653-5p promoted GC cell proliferation and metastasis in vivo and in vitro. Suppressor of cytokine signaling 6 (SOCS6) was directly targeted by miR-653-5p, and SOCS6 attenuated miR-653-5p-mediated GC cell growth, migration, and invasion. In addition, SOCS6-mediated inactivation of the Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling pathway was also reversed by the administration of miR-653-5p. The findings from this study support a novel regulatory axis between miR-653-5p, SOCS6, and JAK2/STAT3 that may be a target for diagnosis and therapeutic intervention for GC.

Correlations of SNHG5 genetic polymorphisms with susceptibility and prognosis to gastric cancer in a Chinese population.

The most studied genetic polymorphisms associated with gastric cancer (GC) risk are located in protein-coding genes. However, these sited in long noncoding RNA (lncRNA) are not adequately explored yet. Here, we designed a case-control study of 848 cases and 880 controls to investigate the associations of polymorphisms (rs61396151, rs1059307, rs11961028, rs9351065) in lncRNA SNHG5 with the risk and prognosis of GC. The results indicate rs61396151 associated with decreased risk of GC (OR = 0.78, 95% CI = 0.62-0.96), but there were no correlations observed with the clinicopathological features of GC (P > 0.05). However, the CA genotype of rs61396151 was correlated with poor overall survival rate in a multivariate cox regression model (HR = 1.91, P = 0.040), but it was reversed with adjustment for age, gender and TNM stage (HR = 1.35, P = 0.213). Collectively, our results highlight the importance of SNHG5-related polymorphisms to GC susceptibility and prognosis.

Dynamic Response of PVDF Cantilever Due to Droplet Impact Using an Electromechanical Model.

The dynamic response of a polyvinylidene fluoride (PVDF) cantilever beam under excitation of water droplet impact is investigated by developing an electromechanical model. In the model, the governing equations of beam motion and output voltage are derived in the theoretical way, such that the voltage across the PVDF layer and the cantilever deflection can be predicted. The motion of the beam is described by the multi-mode vibration model through which more accurate results can be obtained. The predicted results of the model are validated by the experiment. Combined with the experiment and the model, the effect of surface wettability on droplet-substrate interaction mechanisms is investigated, which provides an insight into the improvement of mechanical-to-electrical energy conversion efficiency in raindrop energy harvesting (REH) applications. Results show: (1) the droplet splash on a super-hydrophobic beam surface has a positive effect on voltage generation. The splash limit that affects the reaction force of the impacting droplet is experimentally determined and greatly dominant by the Weber number. (2) Small-scaled droplets in splash regime allow generating higher voltage output from a super-hydrophobic beam surface than from an untreated hydrophilic beam surface. (3) Tests of successive droplet impacts also show that a super-hydrophobic surface performs better over a hydrophilic surface by producing constant peak voltage and higher electrical energy harvested. In this case, the voltage measured from the hydrophilic surface decreases gradually as the water layer is accumulated. Overall, the electromechanical behaviors of a super-hydrophobic PVDF cantilever sensor can be well predicted by the model which shows a great potential in energy harvesting by maximizing the inelastic collision upon droplet-substrate interactions.

All-dielectric bifocal isotropic metalens for a single-shot hologram generation device.

Planar metalenses are regarded as promising functional nanodevices because of their lightweight, nano-resolution properties, and, therefore, they can serve as versatile platforms for imaging and Fourier transforming. Here, we demonstrate a meta-device that functions as an isotropic bifocal all-dielectric Huygens' metalens to realize nanoscale real-time coaxial digital hologram generation. We design an isotropic bifocal metalens for micro/nano hologram recording, and the metalens utilizes the complete region compared to a previously reported interleaved multifocal metalens scheme. In addition, the hologram generation does not depend on complex polarization conversion, thereby improving the practical efficiency. For high-fidelity reconstruction, compressive reconstruction is utilized to remove twin-image and zero-order items and to suppress noise. Such concept would be extended to white-light achromatic meta-holography and three-dimensional micro/nano in vivo incoherent super-resolution imaging under subwavelength modulation.

Long non-coding RNA CCDC144NL-AS1 sponges miR-143-3p and regulates MAP3K7 by acting as a competing endogenous RNA in gastric cancer.

Gastric cancer (GC) has been one of the most leading cause of cancer-death worldwide. Long non-coding RNAs (lncRNAs) have been found to be related with the carcinogenesis and the development of various cancers, including GC. However, there are still many GC-related lncRNAs functional roles and molecular mechanisms that have not yet been clearly studied. Herein, we report lncRNA CCDC144NL-AS1, which has not been explored in GC, and it is markedly upregulated in GC tissues, which may serve as an independent predictor of poor prognosis. We found that CCDC144NL-AS1 expression was significantly positively associated with a larger tumor size and more pronounced lymph node metastasis. Through a series of in vivo and in vitro functional experiments, we observed that CCDC144NL-AS1 could facilitate cell proliferation, invasion and migration and inhibit cell apoptosis in GC. Further mechanism investigation revealed that CCDC144NL-AS1 acted as a competing endogenous RNA (ceRNA) for sponging miR-143-3p and upregulated the expression of its direct endogenous target MAP3K7 in GC. Taken together, our results elucidate the oncogenic roles of CCDC144NL-AS1/miR-143-3p/MAP3K7 axis in GC progression, providing inspiration for further understanding of the mechanism of GC and making CCDC144NL-AS1 as a potential novel diagnostic and therapeutic target for GC.

Long noncoding RNA TRPM2-AS acts as a microRNA sponge of miR-612 to promote gastric cancer progression and radioresistance.

Long noncoding RNAs (lncRNAs) are emerging as important regulators of tumorigenesis and are frequently dysregulated in cancers. Here, we identify a critical lncRNA TRPM2-AS which is aberrantly expressed in gastric cancer (GC) tissues by screening The Cancer Genome Atlas Program(TCGA) database of GC cohort, and its upregulation is clinically associated with advanced pathologic stages and poor prognosis in GC patients. Silencing TRPM2-AS inhibits the proliferation, metastasis and radioresistance of GC cell whereas ectopic expression of TRPM2-AS significantly improves the progression of GC cell in multiple experiments. Mechanistically, TRPM2-AS serves as a microRNA sponge or a competitive endogenous RNA (ceRNA) for tumor suppressive microRNA miR-612 and consequently modulates the derepression of IGF2BP1 and FOXM1. Moreover, induced upregulation of IGF2BP1 subsequently increases the expression of c-Myc and promotes GC cell progression. Meanwhile, TRPM2-AS promotes the radioreistance of GC cell through enhancing the expression of FOXM1 as well. Thus, our findings support a new regulatory axis between TRPM2-AS, miR-612, IGF2BP1, or FOXM1 which serve as crucial effectors in GC tumorigenesis and malignant development, suggesting a promising therapeutic and diagnostic direction for GC.

Application of fermentation process control to increase l-tryptophan production in Escherichia coli.

In this study, process engineering and process control were applied to increase the production of l-tryptophan using Escherichia coli Dmtr/pta-Y. Different dissolved oxygen (DO) and pH control strategies were applied in l-tryptophan production. DO and pH were maintained at [20% (0-20 hr); 30% (20-40 hr)] and [7.0 (0-20 hr), 6.5 (20-40 hr)], respectively, which increased l-tryptophan production, glucose conversion percentage [g (l-tryptophan)/g (glucose)], and transcription levels of key genes for tryptophan biosynthesis and tryptophan biosynthesis flux, and decreased the accumulation of acetate and transcription levels of genes related to acetate synthesis and acetate synthesis flux. Using E. coli Dmtr/pta-Y with optimized DO [20% (0-20 hr); 30% (20-40 hr)] and pH [7.0 (0-20 hr), 6.5 (20-40 hr)] values, the highest l-tryptophan production (52.57 g/L) and glucose conversion percentage (20.15%) were obtained. The l-tryptophan production was increased by 26.58%, the glucose conversion percentage was increased by 22.64%, and the flux of tryptophan biosynthesis was increased to 21.5% compared with different conditions for DO [50% (0-20 hr), 20% (20-40 hr)] and pH [7.0].

STRA6 exerts oncogenic role in gastric tumorigenesis by acting as a crucial target of miR-873.

BACKGROUND: Increasing evidence shows that stimulated by retinoic acid 6 (STRA6) participates in regulating multiple cancers. However, the biological roles of STRA6 in gastric cancer (GC) remain unknown. This study aimed to investigate the biological function of STRA6 and reveal the underlying mechanism of its dysregulation in GC. METHODS: The expression level of STRA6 was detected through quantitative real-time PCR and Western blot analysis. The effects of STRA6 on the proliferation of GC cells were studied through CCK-8 proliferation, colony formation and 5-ethynyl-2'-deoxyuridine (EdU) assays. The effects of STRA6 on migration and invasion were detected via wound healing and Transwell assays. Upstream miRNAs, which might regulate STRA6 expression, was predicted through bioinformatics analysis. Their interaction was further confirmed through dual-luciferase reporter assays and rescue experiments. RESULTS: STRA6 was up-regulated in GC and enhanced the proliferation and metastasis of GC cells in vitro and in vivo. STRA6 knockdown could inhibit the Wnt/ß-catenin signalling pathway. STRA6 was confirmed as an miR-873 target, which acted as a tumour suppressor in GC. Rescue assays showed that the repressing effect of miR-873 could be partially reversed by overexpressing STRA6. CONCLUSIONS: STRA6 is down-regulated by miR-873 and plays an oncogenic role by activating Wnt/ß-catenin signalling in GC.

Association of TP73-AS1 gene polymorphisms with the risk and survival of gastric cancer in a Chinese Han Population.

It was investigated that TP73-AS1(TP73 antisense RNA 1) could function as an oncogene in gastric cancer (GC). The expression and function of long noncoding RNAs (lncRNAs) could be impacted by single nucleotide polymorphisms (SNPs), which are related to cancer susceptibility and prognosis. This study was to reveal the association between lncRNAs TP73-AS1 polymorphisms (rs1181865 A > G, rs9800 G > C, rs3737589 A > G, rs2298222 G > A, rs7515164 C > A) and GC in 1000 GC cases and 1000 controls in a Chinese Han population. Rs3737589 G allele had significant associations with the increasing risk of GC (G vs. A: p = .005). Rs3737589 variant genotypes (AG + GG) were related to an increased risk of GC in the elder population (age ≥60), females, nonsmokers, nondrinkers, individuals living in urban, and individuals without family history of GC in stratified analyses. Rs3737589 variant genotypes (AG + GG) were related to the advanced depth of tumor invasion (T3 + T4). Besides, we found that GC patients with AG or GG genotype of rs3737589 had poorer overall survival (OS) than those with AA genotype (p < .05). Our findings showed that the lncRNA TP73-AS1 rs3737589 polymorphism might increase the risk of GC, and rs3737589 polymorphism could be a potential biomarker to predict the prognosis of GC patients.

SATB1 Promotes Pancreatic Cancer Growth and Invasion Depending on MYC Activation.

BACKGROUND: SATB1 plays an important role in human malignant progression, inducing cancer cell proliferation and metastasis by regulating downstream gene expressions. However, little is known about the underlying mechanisms in which SATB1 promotes pancreatic cancer tumorigenesis. AIMS: To investigate SATB1 expression levels and its biological functions in promoting pancreatic cancer growth and invasion. METHODS: SATB1 expression levels were detected in seven human pancreatic cancer cell lines and 16 pairs of normal pancreatic/pancreatic cancer tissues using RT-PCR and western blot. SW1990 or Capan-1 cells stably knockdown (shRNA) or transiently knockdown (siRNA) SATB1 cells, and PANC-1 stably overexpressing SATB1 cells were investigated with MTT, EdU assay, flow cytometry, and transwell invasion assay for cell proliferation and invasion activity. The binding of SATB1 to MYC promoter region was examined using reporter assay. Expression of SATB1 in 68 pancreatic cancer samples was studied by immunohistochemical staining and scoring. RESULTS: SATB1 was overexpressed in pancreatic cancer tissues samples, showing strong correlation with pancreatic cancer invasion depth and tumor staging. SATB1 induced MYC mRNA and protein expression; promoted pancreatic cancer cell growth; increased cell population in S phase; and enhanced pancreatic cancer cell invasion in vitro. On the other hand, SATB1 knockdown showed opposite effects. Furthermore, MYC blocking in SATB1-overexpressing cells attenuated the promotion of pancreatic cancer cell growth and invasion. Our data also indicated that SATB1 bound to specific promoter region of MYC. CONCLUSIONS: SATB1 is overexpressed in pancreatic cancer, promoting cancer cell proliferation and invasion through the activation of MYC.

PP2A inhibitors arrest G2/M transition through JNK/Sp1- dependent down-regulation of CDK1 and autophagy-dependent up-regulation of p21.

Protein phosphatase 2A (PP2A) plays an important role in the control of the cell cycle. We previously reported that the PP2A inhibitors, cantharidin and okadaic acid (OA), efficiently repressed the growth of cancer cells. In the present study, we found that PP2A inhibitors arrested the cell cycle at the G2 phase through a mechanism that was dependent on the JNK pathway. Microarrays further showed that PP2A inhibitors induced expression changes in multiple genes that participate in cell cycle transition. To verify whether these expression changes were executed in a PP2A-dependent manner, we targeted the PP2A catalytic subunit (PP2Ac) using siRNA and evaluated gene expression with a microarray. After the cross comparison of these microarray data, we identified that CDK1 was potentially the same target when treated with either PP2A inhibitors or PP2Ac siRNA. In addition, we found that the down-regulation of CDK1 occurred in a JNK-dependent manner. Luciferase reporter gene assays demonstrated that repression of the transcription of CDK1 was executed through the JNK-dependent activation of the Sp1 transcription factor. By constructing deletion mutants of the CDK1 promoter and by using ChIP assays, we identified an element in the CDK1 promoter that responded to the JNK/Sp1 pathway after stimulation with PP2A inhibitors. Cantharidin and OA also up-regulated the expression of p21, an inhibitor of CDK1, via autophagy rather than PP2A/JNK pathway. Thus, this present study found that the PP2A/JNK/Sp1/CDK1 pathway and the autophagy/p21 pathway participated in G2/M cell cycle arrest triggered by PP2A inhibitors.

HERG1 functions as an oncogene in pancreatic cancer and is downregulated by miR-96.

Pancreatic cancer is an aggressive malignancy with an extremely poor prognosis. The human ether-a-go-go-related potassium channel (HERG1) is a human rapid delayed rectifier, which is involved in many crucial cellular events. In this article, we find that HERG1 expression is dramatically increased both in pancreatic cancer tissues and cell lines, and that increased HERG1 expression is significantly related to the development of pancreatic cancer. HERG1 silencing in pancreatic cancer-derived cell lines PANC-1 and CFPAC-1 strongly inhibits their malignant capacity in vitro as well as tumorigenicity and metastasis in nude mice. In addition, HERG1 is identified as a direct target of miR-96, which is downregulated in pancreatic cancer tissues and cell lines. Ectopic expression of miR-96 represses the HERG1 expression in pancreatic cancer and significantly inhibits malignant behavior of pancreatic cancer cells in vitro and in vivo. Collectively, our findings suggest that miR-96 acts as a tumor suppressor in pancreatic cancer and may therefore serve as a useful therapeutic target for the development of new anticancer therapy.

MiR-874 promotes intestinal barrier dysfunction through targeting AQP3 following intestinal ischemic injury.

Intestinal ischemic injury is a significant clinical problem arising from diseases or as a complication of abdominal surgery. Our previous study showed aquaporin 3 is involved in intestinal barrier impairment. Here, we revealed that intestinal ischemia induced a time-dependent increase of miR-874 expression and a time-dependent decrease of AQP3 expression, and the level of miR-874 expression was inversely related to AQP3 protein expression. In addition, miR-874 promoted the paracellular permeability in vitro through targeting 3'UTR of AQP3. Two of the tight junction proteins, Occludin and Claudin-1, were found to be involved in miR-874-induced intestinal barrier dysfunction.

miR-874 Inhibits cell proliferation, migration and invasion through targeting aquaporin-3 in gastric cancer.

BACKGROUND: Aquaporin-3 (AQP3) is a water transporting protein which plays an oncogenic role in several malignant tumors. However, its regulatory mechanism remains elusive to date. In this study, we investigated the microRNA-mediated gene repression mechanism involved in AQP3's role. METHODS: The potential microRNAs targeting AQP3 were searched via bioinformatic methods and identified by luciferase reporter assays, microRNA RT-PCR and western blotting. The expression patterns of miR-874 and AQP3 in human gastric cancer (GC) specimens and cell lines were determined by microRNA RT-PCR and western blotting. 5-ethynyl-2'-deoxyuridine, cell migration and invasion assays and tumorigenicity in vivo were adopted to observe the effects of miR-874 depletion or ectopic miR-874 expression on GC cell phenotypes. Cell apoptosis was evaluated by FACS and TUNEL in vitro and in vivo respectively. RESULTS: miR-874 suppressed AQP3 expression by binding to the 3'UTR of AQP3 mRNA in GC cells. miR-874 was significantly down-regulated and reversely correlated with AQP3 protein levels in clinical samples. Analysis of the clinicopathological significance showed that miR-874 and AQP3 were closely correlated with GC characteristics. Functional analyses indicated that ectopic miR-874 expression suppressed the growth, migration, invasion and tumorigenicity of GC cells, whereas miR-874 knockdown promoted these phenotypes. Down-regulation of Bcl-2, MT1-MMP, MMP-2 and MMP-9 and upregulation of caspase-3 activity and Bax were involved in miR-874 inducing cell apoptosis, and inhibiting migration and invasion. CONCLUSIONS: These results provide a mechanism by which AQP3 is upregulated, as well as highlight the importance of miR-874 in gastric cancer development and progression.

[Studies on chemical constituents from leaves of Vaccinium bracteatum].

OBJECTIVE: To investigate the chemical constituents from the leaves of Vaccinium bracteatum. METHOD: Many column chromatographic techniques were used for the isolation and separation of chemical constituents. Their structures were elucidated on the basis of spectral analysis and chemical evidences. RESULT: Twelve compounds were isolated from the plant, and they were identified as chrysoeriol (1), scopoletin (2), trans-p-hydroxycinnamic acid (3), trans-p-hydroxycinnamic acid ethyl ester (4), cafeic acid ethyl ester (5), beta-sitosterol (6), iuteolin (7), quercetin (8), esculetin (9), cafeic acid (10), isolariciresinol-9-O-beta-D-xyloside (11), 10-O-trans-p-coumaroylsandoside (12). CONCLUSION: Compounds 4, 5, 11, 12 were isolated from the genus Vaccinium for the first time, and compounds 1, 2, 9, 10 were isolated from this plant for the first time.