Phosphorylated ATF1 at Thr184 promotes metastasis and regulates MMP2 expression in gastric cancer.

BACKGROUND: Studies have revealed an important role of activating transcription factor 1 (ATF1) and phosphorylated ATF1 at Ser63 in tumors. Our previous study identified Thr184 as a novel phosphorylation site of ATF1. However, the role of phosphorylated ATF1 at Thr184 (p-ATF1-T184) in tumor is unclear. This study figured out the role of p-ATF1-T184 in the metastasis of gastric cancer (GC) and in the regulation of Matrix metallopeptidase 2 (MMP2). METHODS: Immunohistochemical analysis (IHC) was performed to analyze the level of p-ATF1-T184 and its relationship with clinicopathological characteristics. Wound scratch test, Transwell assay were used to observe the role of p-ATF1-T184 in the invasion and metastasis of GC. The regulation of MMP2 by p-ATF1-T184 was investigated by a series of experiments including quantitative RT-PCR, western blot, gelatin zymography assay, Chromatin immunoprecipitation (ChIP), luciferase reporter assay and cycloheximide experiment. The Cancer Genome Atlas (TCGA) data were used to analyze the expression and prognostic role of ATF1 and MMP2 in GC. Mass spectrometry (MS) following co-immunoprecipitation (co-IP) assay was performed to identify potential upstream kinases that would phosphorylate ATF1 at Thr184. RESULTS: High expression level of p-ATF1-T184 was found and significantly associated with lymph node metastasis and poor survival in a GC cohort of 126 patients. P-ATF1-T184 promoted migration and invasion of gastric cancer cells. Phosphorylation of ATF1-T184 could regulate the mRNA, protein expression and extracellular activity of MMP2. P-ATF1-T184 further increased the DNA binding ability, transcription activity, and stabilized the protein expression of ATF1. Moreover, TCGA data and IHC results suggested that the mRNA level of ATF1 and MMP2, and protein level of p-ATF1-T184 and MMP2 could be prognosis markers of GC. Two protein kinase related genes, LRBA and S100A8, were identified to be correlated with the expression ATF1 in GC. CONCLUSION: Our results indicated that p-ATF1-T184 promoted metastasis of GC by regulating MMP2.

A model based on CT radiomic features for predicting RT-PCR becoming negative in coronavirus disease 2019 (COVID-19) patients.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has emerged as a global pandemic. According to the diagnosis and treatment guidelines of China, negative reverse transcription-polymerase chain reaction (RT-PCR) is the key criterion for discharging COVID-19 patients. However, repeated RT-PCR tests lead to medical waste and prolonged hospital stays for COVID-19 patients during the recovery period. Our purpose is to assess a model based on chest computed tomography (CT) radiomic features and clinical characteristics to predict RT-PCR negativity during clinical treatment. METHODS: From February 10 to March 10, 2020, 203 mild COVID-19 patients in Fangcang Shelter Hospital were retrospectively included (training: n = 141; testing: n = 62), and clinical characteristics were collected. Lung abnormalities on chest CT images were segmented with a deep learning algorithm. CT quantitative features and radiomic features were automatically extracted. Clinical characteristics and CT quantitative features were compared between RT-PCR-negative and RT-PCR-positive groups. Univariate logistic regression and Spearman correlation analyses identified the strongest features associated with RT-PCR negativity, and a multivariate logistic regression model was established. The diagnostic performance was evaluated for both cohorts. RESULTS: The RT-PCR-negative group had a longer time interval from symptom onset to CT exams than the RT-PCR-positive group (median 23 vs. 16 days, p < 0.001). There was no significant difference in the other clinical characteristics or CT quantitative features. In addition to the time interval from symptom onset to CT exams, nine CT radiomic features were selected for the model. ROC curve analysis revealed AUCs of 0.811 and 0.812 for differentiating the RT-PCR-negative group, with sensitivity/specificity of 0.765/0.625 and 0.784/0.600 in the training and testing datasets, respectively. CONCLUSION: The model combining CT radiomic features and clinical data helped predict RT-PCR negativity during clinical treatment, indicating the proper time for RT-PCR retesting.

ZBP-89 and Sp1 contribute to Bak expression in hepatocellular carcinoma cells.

BACKGROUND: Kruppel family member zinc binding protein 89 (ZBP-89), also known as ZNF148, regulates Bak expression via binding to GC-rich promoter domain. It is not clear if other GC-rich binding factors, such as Sp family members, can interact with ZBPp-89 on Bak expression. This study aims to elucidate the mechanism of Bak expression regulation by ZBP-89 and Sp proteins, based on in vitro experiment and The Cancer Genome Atlas (TCGA) hepatocellular carcinoma (HCC) data cohort. METHODS: We downloaded TCGA hepatocellular carcinoma (HCC) cohort data to analysis the association of Bak transcription level with ZBP-89 and Sp proteins transcription level. HCC cell lines and liver immortal non-tumour cell lines were used for mechanism study, including western blotting analysis, expression vector mediated gene expression and siRNA interference. RESULTS: Results showed that cancer tissues have higher Bak transcription level compared with adjacent non-cancer tissues. Bak transcription level was correlated with Sp1 and Sp3 expression level, while no correlation was found in ZBP-89 and Bak, neither Sp2 nor Sp4. Mithramycin A (MMA) induced Bak expression in a dose-dependent manner. Western blotting results showed Sp1 overexpression increased Bak expression both in liver immortal non-tumour cells and HCC cells. Interference Sp1 expression could inhibit Bak expression alone. ZBP-89 siRNA suppressed Bak expression even in the presence of MMA treatment and S1 overexpression. Additionally, Bak and Sp1 level were associated with HCC patient survival. CONCLUSIONS: Bak expression required ZBP-89 and Sp1 cooperative regulation simultaneously.

Identification of a novel microRNA signature associated with intrahepatic cholangiocarcinoma (ICC) patient prognosis.

BACKGROUND: The clinical significance of microRNAs (miRNAs) in intrahepatic cholangiocarcinoma (ICC) is unclear. The objective of this study is to examine the miRNA expression profiles and identify a miRNA signature for the prognosis of ICC. METHODS: Using a custom microarray containing 1,094 probes, the miRNA expression profiles of 63 human ICCs and nine normal intrahepatic bile ducts (NIBD) were assessed. The miRNA signatures were established and their clinical significances in ICC were analyzed. The expression levels of some miRNAs were verified by quantitative real-time RT-PCR (qRT-PCR). RESULTS: Expression profile analysis showed 158 differentially expressed miRNAs between ICC and NIBD, with 77 up-regulated and 81 down-regulated miRNAs. From the 158 differentially expressed miRNAs, a 30-miRNA signature consisting of 10 up-regulated and 20 down-regulated miRNAs in ICC was established for distinguishing ICC from NIBD with 100% accuracy. A separate 3-miRNA signature was identified for predicting prognosis in ICC. Based on the 3-miRNA signature, a formula was constructed to compute a risk score for each patient. The patients with high-risk had significantly lower overall survival and disease-free survival than those with low-risk. The expression level of these three miRNAs detected by microarray was verified by qRT-PCR. Multivariate analysis indicated that the 3-miRNA signature was an independent prognostic predictor. CONCLUSIONS: In this study, a 30-miRNA signature for distinguishing ICC from NIBD, and a 3-miRNA signature for evaluating prognosis of ICC were established, which might be able to serve as biomarkers for prognosis of ICC. Further studies focusing on these miRNAs may shed light on the mechanisms associated with ICC pathogenesis and progression.

Association of miR-146a gene polymorphism with risk of nasopharyngeal carcinoma in the central-southern Chinese population.

This case-control study focused on estimating the association between miR-146a polymorphism and risk of nasopharyngeal carcinoma (NPC) in central-south China. In total, 160 patients with NPC and 200 healthy controls in central-south China were genotyped using polymerase chain reaction-restriction fragment length polymorphism assay. Chi-square test was used to assess the different distribution of miR-146a polymorphism between NPC patients and controls; and logistic regression analysis was applied to analyze the associations between miR-146a polymorphism with cancer risk in different contrast models. Significant differences between NPC patients and controls were found in genotype (P=0.033 for GG versus CG versus CC; and odds ratio (OR)=0.568, 95% confidence interval (CI)=0.354-0.912, P=0.019 for CG versus CC; and OR=0.503, 95% CI=0.261-0.971, P=0.041 for CG versus CC; and OR=0.564, 95% CI=0.360-0.884, P=0.012 for GG+CG versus CC, respectively) and allelic analysis (P=0.025 for G versus C). Our findings suggested that polymorphism of mir-146a was associated with NPC in the central-southern Chinese population.

Essential contribution of the JAK/STAT pathway to carcinogenesis, lytic infection of herpesviruses and pathogenesis of COVID­19 (Review).

The intracellular pathway of Janus kinase/signal transducer and activator of transcription (JAK/STAT) and modification of nucleosome histone marks regulate the expression of proinflammatory mediators, playing an essential role in carcinogenesis, antiviral immunity and the interaction of host proteins with Herpesviral particles. The pathway has also been suggested to play a vital role in the clinical course of the acute infection caused by severe acute respiratory syndrome coronavirus type 2 (SARS­CoV­2; known as coronavirus infection­2019), a novel human coronavirus initially identified in the central Chinese city Wuhan towards the end of 2019, which evolved into a pandemic affecting nearly two million people worldwide. The infection mainly manifests as fever, cough, myalgia and pulmonary involvement, while it also attacks multiple viscera, such as the liver. The pathogenesis is characterized by a cytokine storm, with an overproduction of proinflammatory mediators. Innate and adaptive host immunity against the viral pathogen is exerted by various effectors and is regulated by different signaling pathways notably the JAK/STAT. The elucidation of the underlying mechanism of the regulation of mediating factors expressed in the viral infection would assist diagnosis and antiviral targeting therapy, which will help overcome the infection caused by SARS­CoV­2.

Functional interleukin-17 receptor A are present in the thyroid gland in intractable Graves disease.

Th17 lymphocytes and its main cytokine, IL-17, play an important role in autoimmune thyroid diseases, such as intractable Graves disease (GD). IL-17 signals are transmitted through its receptor, IL-17RA. The intrathyroid expression of IL-17RA in intractable GD is not understood. In this study, ELISA was used to measure serum IL-17 levels in patients with untreated GD, intractable GD or GD in remission and healthy controls. Real-time PCR, flow cytometry and immunofluorescence staining evaluated IL-17RA mRNA and protein expression in thyrocytes. IL-6, chemokine ligand 10 (CXCL10) and intercellular adhesion molecule (ICAM)-1 expression was measured in IL-17-stimulated thyrocyte cultures to evaluate the functional status of IL-17RA. Our data indicates that serum IL-17 levels are significantly increased in intractable GD and affected thyrocytes show functional IL-17R expression. These changes facilitate the IL-17-mediated upregulation of IL-6, CXCL10, and ICAM-1. The IL-17/IL-17R interaction could be a potential target for therapeutic interventions in intractable GD.

Association between PIN1 promoter polymorphisms and risk of nasopharyngeal carcinoma.

Peptidylprolyl cis/trans isomerase, NIMA-interacting 1 (PIN1) plays an important role in cell transformation and oncogenesis. Association between PIN1 promoter polymorphisms and cancer risk was reported in several cancers. This study aimed to evaluate the association between two single nucleotide polymorphisms (SNPs, -667T>C, rs2233679 and -842G>C, rs2233678) on PIN1 promoter and risk of nasopharyngeal carcinoma (NPC). The two SNPs were genotyped using polymerase chain reaction-restriction fragment length polymorphism in a total of 334 native Chinese subjects consisting of 178 cases and 156 controls. The results indicated that the -667CT heterozygote and -667CC homozygote exhibited a significantly decreased risk of nasopharyngeal carcinoma when compared with -667TT homozygote (OR = 0.639, 95% CI = 0.452-0.903, p = 0.011 for -667CT; and OR = 0.441, 95% CI = 0.213-0.915, p = 0.038 for -667CC, respectively). In the -842G>C polymorphism, compared with -842GG homozygote, only -842CG heterozygote but not -842CC homozygote had a significantly decreased risk of nasopharyngeal carcinoma (OR = 0.465, 95% CI = 0.249-0.871, p = 0.010). Genotype in the two SNPs in patients showed no significant associations with the clinicopathologic features examined. Our study showed that the minor genotypes of PIN1 promoter (-667CT, -667CC and -842CG) were associated with decreased risk of NPC in a Chinese population, suggested that PIN1 promoter polymorphisms might play an important role in NPC carcinogenesis.

Increased glutathione and mitogen-activated protein kinase phosphorylation are involved in the induction of doxorubicin resistance in hepatocellular carcinoma cells.

AIM: The human hepatocellular carcinoma (HCC) cell line HepG2 can easily acquire resistance to doxorubicin. However, the mechanism of action is unclear. METHODS: In the present study, we used confocal microscopy, flow cytometry and other methods to reveal the mechanisms by which HepG2 cells acquire doxorubicin resistance. RESULTS: Our results showed that R-HepG2 cells, a doxorubicin-resistant sub-line of HepG2, exhibited decreased intracellular accumulation of doxorubicin and increased expression of P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 when compared with HepG2 cells. R-HepG2 cells also harbored higher levels of glutathione and increased expression of glutathione peroxidase. Furthermore, we demonstrated that the phosphorylation of mitogen-activated protein kinases (p38 and c-jun-N-terminal kinases), IkBα and CREB were increased in R-HepG2 cells. Specific p38 inhibitor SB203580 decreased P-gp expression. The multi-kinase inhibitor sorafenib tosylate also significantly suppressed the phosphorylation of these proteins and inhibited the expression of P-gp. CONCLUSION: These findings reveal that the drug resistance could be acquired through mitogen-activated protein kinase-dependent upregulation of P-gp. This mechanism protects R-HepG2 cells from the anticancer action of doxorubicin.

Diagnostic and Prognostic Value of Protein Post-translational Modifications in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is a common malignant tumor with high incidence and cancer mortality worldwide. Post-translational modifications (PTMs) of proteins have a great impact on protein function. Almost all proteins can undergo PTMs, including phosphorylation, acetylation, methylation, glycosylation, ubiquitination, and so on. Many studies have shown that PTMs are related to the occurrence and development of cancers. The findings provide novel therapeutic targets for cancers, such as glypican-3 and mucin-1. Other clinical implications are also found in the studies of PTMs. Diagnostic or prognostic value, and response to therapy have been identified. In HCC, it has been shown that glycosylated alpha-fetoprotein (AFP) has a higher detection rate for early liver cancer than conventional AFP. In this review, we mainly focused on the diagnostic and prognostic value of PTM, in order to provide new insights into the clinical implication of PTM in HCC.

Circulating miR-221 directly amplified from plasma is a potential diagnostic and prognostic marker of colorectal cancer and is correlated with p53 expression.

BACKGROUND AND AIM: Circulating miRNAs exist in serum and plasma and they can be used as a potential noninvasive molecular marker for colorectal cancer (CRC) diagnosis. The present study was to test the availability of direct amplification of miRNAs from plasma without RNA extraction, and to evaluate its clinical application value in CRC. METHODS: Plasma miR-21, miR-221 and miR-222 levels were determined in 103 CRC patients and 37 healthy normal controls by quantitative reverse transcription-polymerase chain reaction. Immunohistochemical staining for p53, carcinoembryonic antigen (CEA), estrogen receptor (ER) and progesterone receptor (PR) was carried out in the same CRC patient cohort. The correlation between miR-221 levels and protein levels of p53, CEA, ER and PR, clinicopathological features or overall survival was analyzed. RESULTS: A standard curve shows a good linearity between the log of sample input and C(T) values over three orders of magnitude of plasma miR-21, miR-221 and miR-222. ROC curve analysis reveals that the plasma levels of miR-221 is a potential biomarker for differentiating CRC patients from controls. Kaplan-Meier curve assessment shows that the elevated plasma miR-221 level is a significant prognostic factor for poor overall survival in CRC patients. The immunohistochemistry analysis demonstrates a significant correlation between plasma miR-221 level and p53 expression. CONCLUSIONS: The direct amplification of plasma miR-221 can be used as a potential noninvasive molecular marker for diagnosis and prognosis of CRC and is correlated with p53 expression.

MiR-200 family and cancer: From a meta-analysis view.

The role of microRNAs (miRNAs) in cancer development was implicated as oncogene or tumor suppressor. One of the miRNA family, the miR-200 family, was mainly characterized as tumor suppressor. However, controversial results were reported. The associations between miR-200 family (consisting of five miRNAs: miR-141/200a/200b/200c/429) and cancer prognosis were inconsistent. Therefore, we conducted a meta-analysis by searching PubMed and Embase databases for studies assessing the association between the expression of miR-200 family and patients' survival of cancers. Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted from the studies and pooled HRs was determined to evaluate the association. This meta-analysis comprised 58 articles with 8107 cancer patients. The overall analysis showed that patients with higher expression of miR-200 family were associated with worse survival (HR = 1.206, 95% CI: 1.115-1.305, p < 0.001). In the stratified analysis, high level of miR-200b and miR-200c was associated with poor patients' survival. In the subgroup analysis, expression of miR-200a and miR-429 was associated with survival of breast cancer and liver cancer, respectively. Expression of miR-141 was found to be associated with favorable patients' survival in pancreatic cancer (HR = 0.275, 95% CI: 0.104-0.727, p = 0.009). In the subgroup analysis of sample type of miR-141, reverse associations with patients' survival were found from tissue (HR = 0.769, 95% CI: 0.597-0.990, p = 0.042) and blood (HR = 1.496, 95% CI: 1.183-1.893, p = 0.001). Our findings revealed that association between miR-200 family and prognosis of various cancer types was significant and the results needed specific interpretation.

The human ATF1 rs11169571 polymorphism associated with risk of nasopharyngeal carcinoma in Southern Chinese populations.

Our previous work reported activating transcription factor 1 (ATF1) is a promotive factor of nasopharyngeal carcinoma (NPC) tumorigenesis. This study is to further explore the association between the human ATF1 rs11169571 polymorphism and the risk of NPC occurrence. The association between ATF1 rs11169571 and risk of NPC occurrence was investigated in clinical samples of 560 patients and 661 controls obtained from southern China with high incidence of NPC. The genotypes were detected by PCR-RFLP. The differential expression activity of alleles -T and -C was analyzed with CNE-2 and C666-1 cells by luciferase reporter assay. Our data suggested that the allelic frequency and genotypes were significantly different between patients and controls. Compared to the TT homozygote, the TC and CC genotypes have been shown to be significantly decreased in NPC patients (OR = 0.494, 95% CI = 0.387-0.629, P < 0.001 and OR = 0.556, 95% CI = 0.364-0.851, P = 0.007, respectively). Compared to the -T allele, the -C allele is a factor of decreased risk in NPC (OR = 0.642, 95% CI = 0.537-0.767, P < 0.001). Luciferase reporter activity revealed that the -T allele confers a higher expression activity than the -C allele in CNE2 cells and C666-1 cells. In conclusion, ATF1 rs11169571 which could affect the expression of ATF1 is associated with NPC risk.

miR-221 inhibits autophagy and targets TP53INP1 in colorectal cancer cells.

Colorectal cancer (CRC) is the third most common cancer and the fourth leading cause of cancer-associated mortalities worldwide. MicroRNAs (miRNAs/miRs) serve important roles in tumor development, progression and metastasis. miR-221 has been reported to modulate proliferation, apoptosis, cell cycle distribution and cell migration in a variety of cancers. However, the function of miR-221 in the autophagy of cancer is unclear. In the present study, the role of miR-221 in the autophagy of CRC cells was investigated and its associated target was identified. Survival analysis using The Cancer Genome Atlas data suggested that a higher expression of miR-221 was associated with poor survival in patients with CRC. A Cell Counting kit-8 assay revealed that miR-221 promoted CRC cell proliferation. Autophagy flux analyzed by microtubule-associated protein 1 light chain 3 (LC3) turnover indicated that miR-221 reduced autophagy in CRC cells using different protease inhibitors (E64d and pepstatin A; Bafilomycin A1) in nutrient-rich medium or under starvation conditions. Tumor protein 53-induced nuclear protein 1 (TP53INP1) was identified as a potential novel target of miR-221 by bioinformative prediction. The protein expression of TP53INP1 was inversely regulated by miR-221 in CRC cells. Furthermore, luciferase activity assays were performed and indicated that miR-221 may regulate the luciferase activity of wild-type TP53INP1 without interfering with the activity of mutant TP53INP1. These data suggested that miR-221 may promote the cell proliferation of CRC via the inhibition of autophagy and targeted TP53INP1.

Association of microRNA-423 rs6505162 C>A polymorphism with susceptibility and metastasis of colorectal carcinoma.

Studies have evaluated the association between the SNP miRNA-423 rs6505162 C>A and cancer risk in several cancers with contradictory outcomes. It was reported that miRNA-423 rs6505162 C>A polymorphism was associated with the overall survival and the recurrence-free survival of colorectal carcinoma. However, no studies have reported the association between miRNA-423 rs6505162 C>A polymorphism and susceptibility of colorectal carcinoma.In this study, we investigated the association between miRNA-423 polymorphism with risk and clinicopathological parameters of colorectal carcinoma. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method was used to genotype 117 colorectal carcinoma patients and 84 healthy controls.Our data indicated the frequencies of rs6505162 genotypes and alleles were significantly different between colorectal carcinoma patients and controls. Compared with CC homozygote, the AC heterozygote exhibited a significantly decreased risk of colorectal carcinoma; and the combination of AC and AA genotype was associated with decreased risk of colorectal carcinoma. The allele distribution of rs6505162 was significantly different between cases and controls. Furthermore, miR-423 rs6505162 C>A genotype showed a significant association with metastasis in patients (P = .022).Our study suggested that miR-423 rs6505162 C>A polymorphism was associated with the susceptibility and metastasis of colorectal carcinoma, and that miR-423 rs6505162 C>A polymorphism might be a potential biomarker for colorectal carcinoma.

Association between problematic Internet use, sleep disturbance, and suicidal behavior in Chinese adolescents.

BACKGROUND AND AIMS: This large-scale study aimed to test (a) associations of problematic Internet use (PIU) and sleep disturbance with suicidal ideation and suicide attempts among Chinese adolescents and (b) whether sleep disturbance mediates the association between PIU and suicidal behavior. METHODS: Data were drawn from the 2017 National School-based Chinese Adolescents Health Survey. A total of 20,895 students' questionnaires were qualified for analysis. The Young's Internet Addiction Test was used to assess PIU, and level of sleep disturbance was measured by the Pittsburgh Sleep Quality Index. Multilevel logistic regression models and path models were utilized in analyses. RESULTS: Of the total sample, 2,864 (13.7%) reported having suicidal ideation, and 537 (2.6%) reported having suicide attempts. After adjusting for control variables and sleep disturbance, PIU was associated with an increased risk of suicidal ideation (AOR = 1.04, 95% CI = 1.03-1.04) and suicide attempts (AOR = 1.03, 95% CI = 1.02-1.04). Findings of the path models showed that the standardized indirect effects of PIU on suicidal ideation (standardized ß estimate = 0.092, 95% CI = 0.082-0.102) and on suicide attempts (standardized ß estimate = 0.082, 95% CI = 0.068-0.096) through sleep disturbance were significant. Conversely, sleep disturbance significantly mediated the association of suicidal behavior on PIU. DISCUSSION AND CONCLUSIONS: There may be a complex transactional association between PIU, sleep disturbance, and suicidal behavior. The estimates of the mediator role of sleep disturbance provide evidence for the current understanding of the mechanism of the association between PIU and suicidal behavior. Possible concomitant treatment services for PIU, sleep disturbance, and suicidal behavior were recommended.

Simultaneous multi-band valley-protected topological edge states of shear vertical wave in two-dimensional phononic crystals with veins.

The introduction of the concept of valley pseudospin to phononic crystals has made a remarkable topologically protected interface transport of sound, which opens a novel research area referred to as valley Hall topological insulators. Here, we demonstrate the simultaneous multi-band edge states of shear vertical waves in two-dimensional phononic crystals with veins. The multi-band edge states are topologically valley-protected and are obtained by simultaneously gapping multiple Dirac points at K (or K') under the inversion symmetry breaking. As the relative radius of the two adjacent steel columns varies, the band diagram undergoes a topological transition which can be characterized by topological charge distributions and opposite valley Chern numbers. Subsequently, the vortex chirality of the bulk valley modes is unveiled. With numerical simulations, simultaneous multi-band valley dependent edge states and the associated valley-protected backscattering suppression around the curved waveguide are further demonstrated. Our work could become a promising platform for applications of multi-functional topological acoustic devices.

Epigallocatechin-3-gallate Modulates MicroRNA Expression Profiles in Human Nasopharyngeal Carcinoma CNE2 Cells.

BACKGROUND: Epigallocatechin-3-gallate (EGCG) has exhibited antitumor properties in several types of cancers, including nasopharyngeal carcinoma (NPC), but the molecular mechanisms underlying this function remain incompletely understood. The aim of the present study was to characterize the global impact of EGCG on the expression of microRNAs (miRNAs) in NPC cells. METHODS: Using microarray analysis, the alterations of miRNA expression profiles were investigated in EGCG-treated CNE2 cells. Furthermore, the target genes and signaling pathways regulated by EGCG-specific miRNAs were identified using target prediction program and gene ontology analysis. RESULTS: A total of 14 miRNAs exhibited >2-fold expression changes in a dose-dependent manner after treatment with 20 µmol/L and 40 µmol/L EGCG. Totally 43, 49, and 52 target genes from these differentially expressed miRNAs were associated with the apoptosis, cell cycle regulation, and cell proliferation, respectively. A total of 66 signaling pathways, primarily involved in cancer development and lipid and glucose metabolism, were shown to be regulated by EGCG-specific miRNAs. CONCLUSION: EGCG induces considerable alterations of miRNA expression profiles in CNE2 cells, which provides mechanistic insights into cellular responses and antitumor activity mediated by EGCG.

Identification of microRNA-615-3p as a novel tumor suppressor in non-small cell lung cancer.

Lung cancer is the most frequent cause of mortality in cancer patients; non-small-cell lung cancer (NSCLC) accounts for ~80% of lung cancer cases. MicroRNAs (miRNAs) have been revealed to perform an important role in cancer development and progression. Based on a custom miRNA microarray analysis of patients with NSCLC, miRNA-615-3p (miR-615-3p) downregulation was identified in NSCLC tissues compared with normal lung tissues, which suggested that miR-615-3p acted as a tumor suppressor in lung cancer. The overexpression of miR-615-3p was then validated using 40 pairs of NSCLC and adjacent normal tissue samples using a TaqMan reverse transcription-quantitative polymerase chain reaction assay. In order to investigate the tumor suppressor function of miR-615-3p, the ectopic expression of miR-615-3p in the NSCLC A549, H1299 and H1650 cell lines was established. The results revealed that overexpressed miR-615-3p markedly inhibited cell proliferation and colony formation in the 3 NSCLC cell lines compared with the cells overexpressing the negative control sequence (NC). Additional investigation revealed that miR-615-3p overexpression significantly induced apoptosis and cell cycle arrest at the G1 phase in the A549, H1299 and H1650 cell lines compared with the cells overexpressing NC. Finally, ectopic expression of miR-615-3p was found to repress the cell migration and invasion of the 3 lung cancer cell lines. The results of the present study demonstrate, for the first time, that miR-615-3p functions as a tumor suppressor in NSCLC, and may be a novel potential molecular therapeutic target for patients with NSCLC.

The mediating effects of depressive symptoms and sleep quality on the relationship between the non-medical use of prescription drugs and suicidal behaviors among Chinese adolescents.

BACKGROUND: The nature of the relationship between the non-medical use of prescription drugs (NMUPD) and suicide has not been clearly elucidated. Some studies have suggested that the relationship between substance use and suicidal ideation may be spurious and could be explained by other variables. METHODS: A school-based cross-sectional study was performed in Guangzhou. A total of 5853 students completed questionnaires and were included in the study. NMUPD, alcohol use, illicit drug use, depressive symptoms, sleep quality, and suicidal behaviors were assessed. The mediating effects of depressive symptoms and sleep quality on the relationship between NMUPD and suicidal behaviors were examined using a structural equation model. RESULTS: In the simple model without mediation, a positive relationship between NMUPD and suicidal behaviors in adolescents was found, which was independent of effects from the use of other substances. Both depressive symptoms and sleep quality were significant mediators of this relationship. CONCLUSION: Public health and educational professionals should survey depressive symptoms and sleep quality and provide interventions when managing suicidal behaviors among adolescents engaging in NMUPD.