ResearchPad - primary-research https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[The assessment of stress level, anxiety, depressive symptoms, and defense mechanisms among Polish and English medical students]]> https://www.researchpad.co/article/elastic_article_12786 Medical education is proven to be associated with a high degree of psychological stress. Different coping strategies used by students have been investigated on their efficacy. So far, studies on medical students have been limited to a single population.Aim of the studyOur study aimed to identify differences in the prevalence of depressive symptoms, anxiety, stress levels, and defense mechanisms among two groups of medical students, the Polish and English-speaking divisions.Materials and methodsThe study included two groups of first-year medical students, the Polish and English-speaking divisions, comprising 305 participants (n = 204 Polish, n = 101 English, men = 127, women = 176). It was divided into two periods: the students received author questionnaires during an exam-free academic period and then completed the same questionnaires during an exam session. The survey contained questions pertaining to demographics and studying habits among participants and included the Defense Style Questionnaire and Depression Anxiety Stress Scales. Data were analyzed using STATISTICA version 12.0, and p ≤ 0.05 was considered significant.ResultsPolish medical students presented with significantly increased overall stress levels (p = 0.007858) and depressive symptoms (p = 0.030420) compared to the English division students. Polish students also presented with more symptoms of stress, depression, and anxiety during the exam period compared to the exam-free period (p = 0.000625), which did not apply to the English-speaking students. The English division students reached higher scores in the mature defense mechanisms section than the Polish students (p = 0.000001). The use of mature defense mechanisms correlated negatively with the intensity of stress, anxiety, and depressive symptoms in both groups, while immature defense mechanisms promoted higher values of those variables (p = 0.000001).ConclusionsOur study showed significant and multidirectional differences between medical students of the Polish and English divisions attending the same university. Such results could suggest that strategies aimed at reducing depressive symptoms among medical students ought to be adapted towards the needs of a specific population. ]]> <![CDATA[Elevated <i>TNFRSF4</i> gene expression is a predictor of poor prognosis in non-M3 acute myeloid leukemia]]> https://www.researchpad.co/article/elastic_article_12713 We used bioinformatic tools to dichotomize 157 non-M3 AML patients from the TCGA dataset based on the presence or absence of TP53 mutations, and screened out a key gene related to TP53 mutation for future analysis.MethodsDEGs were analyzed by R package “DESeq2” and then run GSEA, GO enrichment, KEGG pathway and PPI network. Hub genes were selected out according to MCC. Log-rank (Mantel–Cox) test was used for survival analysis. Mann–Whitney U’s nonparametric t test and Fisher’s exact test was used for continuous and categorical variables respectively. p value< 0.05 was considered to be statistical significance.ResultsTNFRSF4 was final screened out as a key gene. Besides TP53 mutation (p = 0.0118), high TNFRSF4 was also associated with FLT3 mutation (p = 0.0102) and NPM1 mutation (p = 0.0024). Elevated TNFRSF4 was significantly related with intermediate (p = 0.0004) and poor (p = 0.0011) risk stratification as well as relapse statute (p = 0.0099). Patients with elevated TNFRSF4 expression had significantly shorter overall survival (median survival: 2.35 months vs. 21 months, p < 0.0001). Based on our clinical center data, TNFRSF4 expression was significantly higher in non-M3 AML patients than HDs (p = 0.0377) and MDS patients (EB-1, 2; p = 0.0017).ConclusionsElevated TNFRSF4 expression was associated with TP53, FLT3 and NPM1 mutation as well as poor clinical outcome. TNFRSF4 expression was significantly higher in non-M3 AML patients than HDs and MDS (EB-1, 2) patients. TNFRSF4 is need for future functional and mechanistic studies to investigate the role in non-M3 AML. ]]> <![CDATA[A glycolysis-based 4-mRNA signature correlates with the prognosis and cell cycle process in patients with bladder cancer]]> https://www.researchpad.co/article/elastic_article_9897 Bladder cancer is one of the most prevalent malignancies worldwide. However, traditional indicators have limited predictive effects on the clinical outcomes of bladder cancer. The aim of this study was to develop and validate a glycolysis-related gene signature for predicting the prognosis of patients with bladder cancer that have limited therapeutic options.MethodsmRNA expression profiling was obtained from patients with bladder cancer from The Cancer Genome Atlas (TCGA) database. Gene set enrichment analysis (GSEA) was conducted to identify glycolytic gene sets that were significantly different between bladder cancer tissues and paired normal tissues. A prognosis-related gene signature was constructed by univariate and multivariate Cox analysis. Kaplan–Meier curves and time-dependent receiver operating characteristic (ROC) curves were utilized to evaluate the signature. A nomogram combined with the gene signature and clinical parameters was constructed. Correlations between glycolysis-related gene signature and molecular characterization as well as cancer subtypes were analyzed. RT-qPCR was applied to analyze gene expression. Functional experiments were performed to determine the role of PKM2 in the proliferation of bladder cancer cells.ResultsUsing a Cox proportional regression model, we established that a 4-mRNA signature (NUP205, NUPL2, PFKFB1 and PKM) was significantly associated with prognosis in bladder cancer patients. Based on the signature, patients were split into high and low risk groups, with different prognostic outcomes. The gene signature was an independent prognostic indicator for overall survival. The ability of the 4-mRNA signature to make an accurate prognosis was tested in two other validation datasets. GSEA was performed to explore the 4-mRNA related canonical pathways and biological processes, such as the cell cycle, hypoxia, p53 pathway, and PI3K/AKT/mTOR pathway. A heatmap showing the correlation between risk score and cell cycle signature was generated. RT-qPCR revealed the genes that were differentially expressed between normal and cancer tissues. Experiments showed that PKM2 plays essential roles in cell proliferation and the cell cycle.ConclusionThe established 4‑mRNA signature may act as a promising model for generating accurate prognoses for patients with bladder cancer, but the specific biological mechanism needs further verification. ]]> <![CDATA[Recording of cardiovascular risk factors by general practitioners in patients with schizophrenia]]> https://www.researchpad.co/article/elastic_article_9678 Patients with schizophrenia and related disorders (SRD) are more predisposed to having cardiovascular risk factors (CVRFs) compared to the general population due to a combination of lifestyle factors and exposure to antipsychotic medications. We aimed to analyse the documentation practices of CVRFs by general practitioners (GPs) and its associations with patient variables in a sample of persons with SRD.MethodsAn observational, cross-sectional study was conducted in 13 primary care centres (PCCs) in Malaga (Spain). The population comprised all patients with SRD who were in contact with a GP residing in the study area. The number of CVRFs (type 2 diabetes mellitus, hypertension, hypercholesterolaemia, obesity and smoking) recorded by GPs were analysed by considering patients’ demographic and clinical variables and use of primary care services. We performed descriptive, bivariate and multivariate regression analyses.ResultsA total of 494 patients were included; CVRFs were not recorded in 59.7% of the patients. One CVRF was recorded in 42.1% of patients and two or more CVRFs were recorded in 16.1% of patients. Older age, living in an urban area and a higher number of visits to the GP were associated with a higher number of CVRFs recorded.ConclusionThe main finding in this study is that both patients’ demographic variables as well as use of primary care services were found to be related to the documentation of CVRFs in patients with SRD by GPs. ]]> <![CDATA[Hsa_circ_0068307 mediates bladder cancer stem cell-like properties via miR-147/c-Myc axis regulation]]> https://www.researchpad.co/article/elastic_article_9637 Circular RNAs (circRNAs) play an essential role in the regulation of gene expression. However, the underlying mechanisms remain unknown. This study aimed to evaluate the role of hsa_circ_0068307 in bladder cancer (BCa).MethodsRt-qPCR was used to detect hsa_circ_0068307 expression in BCa cell lines. The CCK8, colony formation, and Transwell assays were used to evaluate the effect of hsa_circ_0068307 on BCa cell migration and proliferation. Bioinformatics and luciferase reporter experiments were used to study the regulatory mechanism. Nude mouse xenografts were generated to examine the effect of hsa_circ_0068307 on tumor growth.ResultsThe results showed that hsa_circ_0068307 was upregulated in BCa cell lines. Downregulation of hsa_circ_0068307 suppressed cell migration and proliferation in T24 and UMUC3 cells. Hsa_circ_0068307 silencing suppressed cancer stem cell differentiation by upregulating miR-147 expression. Upregulation of miR-147 suppressed c-Myc expression, which is involved in cancer stem cell differentiation. Luciferase reporter assays confirmed that hsa_circ_0068307 upregulated c-Myc expression by targeting miR-147. In vivo studies showed that hsa_circ_0068307 knockdown suppressed T24 tumor growth.ConclusionsThese data indicate that downregulation of hsa_circ_0068307 reversed the stem cell-like properties of human bladder cancer through the regulation of the miR-147/c-Myc axis. ]]> <![CDATA[High expression of ESRP1 regulated by circ-0005585 promotes cell colonization in ovarian cancer]]> https://www.researchpad.co/article/elastic_article_9620 Ovarian cancer is the third most common gynecological cancer in the world but the leading cause of death among gynecological malignancies. Epithelial splicing regulatory protein-1 (ESRP1), a key negative splicing regulator in epithelial-mesenchymal transition (EMT), has been proven to be overexpressed and may plays a role in epithelial ovarian cancer (EOC) progression. However, the functional roles of ESRP1 and the underlying mechanisms in this process still remain unclear.MethodsTumor invasion, migration, colony formation and animal experiments were used to study the malignant biological behavior of ESRP1. A vector-based system expressing circ-0005585 was established to investigate circRNA as a microRNAs sponge. RNA-Seq and cytoskeleton staining explored underlying mechanisms of ESRP1.ResultsOur results demonstrated that circ-0005585 regulates ESRP1 overexpression via sponging miR-23a/b and miR-15a/15b/16. Overexpression of ESRP1 suppresses EOC cell migration, but promotes colonization and drives a switch from mesenchymal to epithelial phenotype (MET) in association with actin cytoskeleton reorganization, mainly by alternative splicing EPB41L5 and RAC1. Furthermore, we have shown that high ESRP1 expression may be associated with immune-suppression in tumor immune microenvironment in vivo.ConclusionsESRP1 overexpression promotes MET status and correlates with actin cytoskeleton reorganization in EOC. ESRP1 plays an important role in EOC colonization. In addition, a miRs panel from two miR families can inhibit ESRP1, may provide an innovative approach for cancer theranostics. ]]> <![CDATA[FENDRR suppresses cervical cancer proliferation and invasion by targeting miR-15a/b-5p and regulating TUBA1A expression]]> https://www.researchpad.co/article/elastic_article_9605 Previous literature has revealed long non-coding RNAs (lncRNAs) are crucial regulators for cell functions and gene expression. LncRNA fetal-lethal non-coding developmental regulatory RNA (FENDRR) was reported as a biological suppressor in several types of human cancers, yet relevant mechanisms and biological effects of FENDRR with regards to cervical cancer (CC) are not explored until now.MethodsIn this study, quantitative real-time polymerase chain reaction (qRT-PCR) analysis detected gene expression in tissues and cells. Gain- or loss-of-function experiments revealed the biological effects of FENDRR and miR-15a/b-5p on CC cell functions. Bioinformatics tools were used to predict the relevant genes. Mechanism experiments including RNA immunoprecipitation (RIP) assay, pull down assay and luciferase reporter assay depicted the binding situation and coexistence of indicated genes.ResultsFENDRR was downregulated in CC tissues and cells, which suppressed CC progression. MiR-15a-5p and miR-15b-5p shared binding sites with FENDRR and had interaction with FENDRR. Tubulin alpha1A (TUBA1A) was downregulated in CC tissues and positively modulated by FENDRR. TUBA1A was the target of miR-15a/b-5p. TUBA1A silencing rescued the effect of FENDRR overexpression on CC cell growth and migration.ConclusionFENDRR inhibits CC progression through upregulating TUBA1A in a miR-15a/b-5p-dependent manner. ]]> <![CDATA[<i>OSskcm</i>: an online survival analysis webserver for skin cutaneous melanoma based on 1085 transcriptomic profiles]]> https://www.researchpad.co/article/elastic_article_9549 Cutaneous melanoma is one of the most aggressive and lethal skin cancers. It is greatly important to identify prognostic biomarkers to guide the clinical management. However, it is technically challenging for untrained researchers to process high dimensional profiling data and identify potential prognostic genes in profiling datasets.MethodsIn this study, we developed a webserver to analyze the prognostic values of genes in cutaneous melanoma using data from TCGA and GEO databases. The webserver is named Online consensus Survival webserver for Skin Cutaneous Melanoma (OSskcm) which includes 1085 clinical melanoma samples. The OSskcm is hosted in a windows tomcat server. Server-side scripts were developed in Java script. The database system is managed by a SQL Server, which integrates gene expression data and clinical data. The Kaplan–Meier (KM) survival curves, Hazard ratio (HR) and 95% confidence interval (95%CI) were calculated in a univariate Cox regression analysis.ResultsIn OSskcm, by inputting official gene symbol and selecting proper options, users could obtain KM survival plot with log-rank P value and HR on the output web page. In addition, clinical characters including race, stage, gender, age and type of therapy could also be included in the prognosis analysis as confounding factors to constrain the analysis in a subgroup of melanoma patients.ConclusionThe OSskcm is highly valuable for biologists and clinicians to perform the assessment and validation of new or interested prognostic biomarkers for melanoma. OSskcm can be accessed online at: http://bioinfo.henu.edu.cn/Melanoma/MelanomaList.jsp. ]]> <![CDATA[Circular RNA circ-MAT2B facilitates glycolysis and growth of gastric cancer through regulating the miR-515-5p/HIF-1α axis]]> https://www.researchpad.co/article/elastic_article_9330 Circular RNAs (circRNAs) are a special kind of non-coding RNAs that are implicated in cancer malignant behavior, including glycolysis. However, their contributions to gastric cancer (GC) cell glycolysis are still poorly understood. In the present study, we aimed to investigate the glycolysis-related role of circ-MAT2B in GC.MethodsGene expression was determined by qRT-PCR analysis. Protein level was detected by Western blot. The CCK-8, colony and EdU assays were carried out to assess GC cell viability, colony formation and DNA synthesis rate. Glycolysis was determined by glucose uptake and lactate production. The positive regulatory network of circ-MAT2B/miR-515-5p/HIF-1α was identified by RNA pull-down, RIP, ChIP and luciferase reporter assays. The in vivo role of circ-MAT2B was evaluated by using xenograft tumor model.ResultsCirc-MAT2B was notably increased in GC and could be used as a sensitive and specific indicator of GC diagnosis and prognosis. Stable knockdown of circ-MAT2B dramatically inhibited GC cell viability, colony formation, DNA synthesis, glucose uptake and lactate production in vitro, and retarded tumor growth in vivo. Mechanistically, circ-MAT2B was dominantly located in the cytoplasm and acted as a ceRNA to sponge miR-515-5p and increase HIF-1α expression. Silencing of miR-515-5p or overexpression of HIF-1α could evidently rescue the attenuated aggressive phenotype of GC cells caused by circ-MAT2B knockdown. Importantly, HIF-1α was able to directly bind to circ-MAT2B promoter and transcriptionally activate circ-MAT2B, thus forming a positive feedback loop.ConclusionOur data suggest that circ-MAT2B is a oncogenic circRNA in GC and provide a promising therapeutic target for GC patients. ]]> <![CDATA[<i>N</i>-alkylisatin-based microtubule destabilizers bind to the colchicine site on tubulin and retain efficacy in drug resistant acute lymphoblastic leukemia cell lines with less in vitro neurotoxicity]]> https://www.researchpad.co/article/elastic_article_9262 Drug resistance and chemotherapy-induced peripheral neuropathy continue to be significant problems in the successful treatment of acute lymphoblastic leukemia (ALL). 5,7-Dibromo-N-alkylisatins, a class of potent microtubule destabilizers, are a promising alternative to traditionally used antimitotics with previous demonstrated efficacy against solid tumours in vivo and ability to overcome P-glycoprotein (P-gp) mediated drug resistance in lymphoma and sarcoma cell lines in vitro. In this study, three di-brominated N-alkylisatins were assessed for their ability to retain potency in vincristine (VCR) and 2-methoxyestradiol (2ME2) resistant ALL cell lines. For the first time, in vitro neurotoxicity was also investigated in order to establish their suitability as candidate drugs for future use in ALL treatment.MethodsVincristine resistant (CEM-VCR R) and 2-methoxyestradiol resistant (CEM/2ME2-28.8R) ALL cell lines were used to investigate the ability of N-alkylisatins to overcome chemoresistance. Interaction of N-alkylisatins with tubulin at the the colchicine-binding site was studied by competitive assay using the fluorescent colchicine analogue MTC. Human neuroblastoma SH-SY5Y cells differentiated into a morphological and functional dopaminergic-like neurotransmitter phenotype were used for neurotoxicity and neurofunctional assays. Two-way ANOVA followed by a Tukey’s post hoc test or a two-tailed paired t test was used to determine statistical significance.ResultsCEM-VCR R and CEM/2ME2-28.8R cells displayed resistance indices of > 100 to VCR and 2-ME2, respectively. CEM-VCR R cells additionally displayed a multi-drug resistant phenotype with significant cross resistance to vinblastine, 2ME2, colchicine and paclitaxel consistent with P-gp overexpression. Despite differences in resistance mechanisms observed between the two cell lines, the N-alkylisatins displayed bioequivalent dose-dependent cytotoxicity to that of the parental control cell line. The N-alkylisatins proved to be significantly less neurotoxic towards differentiated SH-SY5Y cells than VCR and vinblastine, evidenced by increased neurite length and number of neurite branch points. Neuronal cells treated with 5,7-dibromo-N-(p-hydroxymethylbenzyl)isatin showed significantly higher voltage-gated sodium channel function than those treated with Vinca alkaloids, strongly supportive of continued action potential firing.ConclusionsThe N-alkylisatins are able to retain cytotoxicity towards ALL cell lines with functionally distinct drug resistance mechanisms and show potential for reduced neurotoxicity. As such they pose as promising candidates for future implementation into anticancer regimes for ALL. Further in vivo studies are therefore warranted. ]]> <![CDATA[Clinicopathological and prognostic significance of nestin expression in patients with breast cancer: a systematic review and meta-analysis]]> https://www.researchpad.co/article/elastic_article_8997 Nestin has been revealed to promote tumorigenesis, progression, metastasis, and angiogenesis of breast cancer. Although the prognostic and clinicopathological impact of nestin expression on breast cancer patients has been assessed in several independent studies, their results remained conflicting. Therefore, we performed this meta-analysis to elucidate the prognostic and clinicopathological association of nestin expression with breast cancer.MethodsA comprehensive literature search was performed in the electronic databases PubMed, EMBASE, Web of Science, the Cochrane Library, China National Knowledge Infrastructure (CNKI), and the Wangfang Data. The statistical analysis was conducted using Stata 15.0 and Review Manager 5.3.ResultsA total of 15 studies with 6066 breast cancer patients were included in this meta-analysis. Pooled results indicated that positive expression of nestin was significantly associated with reduced breast cancer-specific survival (BCSS, univariate analysis, HR = 2.11, 95% CI [1.79, 2.49], P < 0.00001; multivariate analysis, HR = 1.30, 95% CI [1.06, 1.60], P = 0.01), worse overall survival (OS, univariate analysis, HR = 1.88, 95% CI [1.31, 2.71], P = 0.0007; multivariate analysis, HR = 1.89, 95% CI [1.34, 2.67], P = 0.0003) and poorer recurrence-free survival (univariate analysis, HR = 2.60, 95% CI [1.52, 4.46], P = 0.0005), but not with distant metastasis-free survival in univariate analysis (P > 0.05). In addition, increased nestin expression was correlated with younger age, higher tumor grade, larger tumor size, positive blood vessel invasion and high vascular proliferation index, but not with lymph node metastasis or lymph vessel invasion. Nestin was preferentially expressed in invasive ductal carcinoma, triple-negative breast cancer and basal-like subtypes. Nestin expression was inversely associated with the expression of ER and PR, but not with HER-2. Conversely, nestin expression was positively correlated with the expression of basal-like markers CK5, P-cadherin and EGFR. Moreover, nestin expression was strongly associated with the presence of five basal-like profiles (BLP1-5).ConclusionsThis meta-analysis revealed the prognostic value and clinicopathological significance of nestin expression in breast cancer. Nestin is an independent prognostic factor for worse BCSS and OS of breast cancer patients. Nestin is also a valuable biomarker for unfavorable clinicopathological features and tumor angiogenesis of breast cancer. Therefore, nestin is a promising therapeutic target for malignant breast cancer, especially for TNBC and basal-like phenotype. ]]> <![CDATA[Prognostic role of alternative splicing events in head and neck squamous cell carcinoma]]> https://www.researchpad.co/article/elastic_article_8638 Aberrant alternative splicing (AS) is implicated in biological processes of cancer. This study aims to reveal prognostic AS events and signatures that may serve as prognostic predictors for head and neck squamous cell carcinoma (HNSCC).MethodsPrognostic AS events in HNSCC were identified by univariate COX analysis. Prognostic signatures comprising prognostic AS events were constructed for prognosis prediction in patients with HNSCC. The correlation between the percent spliced in (PSI) values of AS events and the expression of splicing factors (SFs) was analyzed by Pearson correlation analysis. Gene functional annotation analysis was performed to reveal pathways in which prognostic AS is enriched.ResultsA total of 27,611 AS events in 15,873 genes were observed, and there were 3433 AS events in 2624 genes significantly associated with overall survival (OS) for HNSCC. Moreover, we found that AS prognostic signatures could accurately predict HNSCC prognosis. SF-AS regulatory networks were constructed according to the correlation between PSI values of AS events and the expression levels of SFs.ConclusionsOur study identified prognostic AS events and signatures. Furthermore, it established SF-AS networks in HNSCC that were valuable in predicting the prognosis of patients with HNSCC and elucidating the regulatory mechanisms underlying AS in HNSCC. ]]> <![CDATA[Mangrove blue carbon stocks and dynamics are controlled by hydrogeomorphic settings and land‐use change]]> https://www.researchpad.co/article/elastic_article_8308 We present blue carbon (C) assessment from 255 plots covering undisturbed and land‐use change‐affected mangroves (0‐, 5‐, 10‐, 15‐ and 25‐year‐old post‐harvest as well as 15‐year‐old aquaculture ponds) across West Papua Province, Indonesia. Undisturbed mangroves stored total ecosystem C‐stocks of 182–2,730 (1,087 ± 584) Mg C/ha, with variation driven by hydrogeomorphic settings. Forest harvesting did not significantly affect soil C‐stocks, despite increased dead wood density, but it removed nearly all live biomass. Aquaculture conversion removed 60% of soil and 85% of live biomass C‐stocks. Mangroves left to regenerate for 25 years reached the same level of biomass carbon compared to undisturbed forests.

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<![CDATA[TUG1/miR-133b/CXCR4 axis regulates cisplatin resistance in human tongue squamous cell carcinoma]]> https://www.researchpad.co/article/N5aac5230-23d8-4b42-b279-dbac45d256bf Long noncoding RNA taurine upregulated 1 (TUG1) has been reported to play an important role in human cancers. However, little is known about the role of TUG1 in drug resistance and its mechanism in tongue squamous cell carcinoma (TSCC).MethodsTwenty-one cisplatin-sensitive or resistant TSCC patients were enrolled in this study. Cisplatin-resistant cells (SCC25/CDDP and CAL27/CDDP) were used for experiments in vitro. Transfection was performed using Lipofectamine 2000 transfection reagent. The levels of TUG1, microRNA-133b (miR-133b) and cysteine-X-cysteine chemokine receptor 4 (CXCR4) were measured by quantitative real-time polymerase chain reaction or western blot. The cisplatin resistance was investigated by cell viability, transwell invasion and apoptosis assays. The interactions among TUG1, miR-133b and CXCR4 were evaluated by luciferase reporter assay and RNA immunoprecipitation. Murine xenograft model was established using the stably transfected CAL27/CDDP cells.ResultsTUG1 expression was elevated in cisplatin-resistant TSCC tissues and cells compared with that in sensitive group and its knockdown inhibited cisplatin resistance to SCC25/CDDP and CAL27/CDDP cells. miR-133b was targeted via TUG1 and its overexpression suppressed cisplatin resistance. Moreover, CXCR4 was a target of miR-133b. CXCR4 silence repressed cisplatin resistance, which was reversed by miR-133b knockdown. The level of CXCR4 protein was decreased by inhibition of TUG1 and recuperated by miR-133b knockdown. Besides, interference of TUG1 attenuated tumor growth by regulating miR-133b and CXCR4 in vivo.ConclusionDownregulation of TUG1 impeded cisplatin resistance in TSCC-resistant cells by mediating miR-133b and CXCR4, indicating TUG1 as a promising target for TSCC chemotherapy. ]]> <![CDATA[Long non-coding RNA LINC01419 mediates miR-519a-3p/PDRG1 axis to promote cell progression in osteosarcoma]]> https://www.researchpad.co/article/Nfce5f474-67fe-4971-b455-35b27ca62990 Osteosarcoma (OS) is one of the most aggressive malignancies with mortality rate worldwide. Accumulating evidence has revealed that long noncoding RNAs (lncRNAs) exert important functions in regulation of cancer initiation and progression. Recently, long intergenic non-protein coding RNA 1419 (LINC01419) has been reported to function as an oncogene in several cancers. However, its role in OS has not been explored yet.MethodsqRT-PCR and western blot analyses were implemented to determine the expression of genes. The function of OS cells was assessed through colony formation, EdU, JC-1, TUNEL, transwell, and immunofluorescence (IF) assays. FISH and subcellular fractionation assays were conducted to estimate the localization of LINC01419 in OS cells. The interaction between genes was validated through luciferase reporter and RNA pull down assays.ResultsLINC01419 expression was elevated in OS tissues and cells. Functionally, LINC01419 accelerated OS cell proliferation, motility and EMT. In vivo assay showed that silencing LINC01419 hindered the growth of OS tumors. Mechanistic investigation unveiled that LINC01419 acted as a competing endogenous RNA (ceRNA) to augment PDRG1 expression by miR-519a-3p sequestration. Rescue assays verified the oncogenic effect of LINC01419/miR-519a-3p/PDRG1 axis on OS development.ConclusionLINC01419 mediates malignant phenotypes in OS by targeting miR-519a-3p/PDRG1 axis. ]]> <![CDATA[LncRNA IGBP1-AS1/miR-24-1/ZIC3 loop regulates the proliferation and invasion ability in breast cancer]]> https://www.researchpad.co/article/Nf17817f3-167a-4774-b198-ce7c701131e4 Breast cancer (BC) is one of the malignant solid tumors with the highest morbidity in the world. Currently, the therapeutic outcome of different types of treatment can be unsatisfactory. Novel lncRNA biomarkers in BC remains to be further explored.MethodsDifferent expression of lncRNAs among BC tissues and adjacent normal tissues were identified with microarray analyses. A series of in vivo and in vitro gain-of-function laboratory procedures were conducted to study the biological functions of IGBP1-AS1. The prognostic effects on IGBP1-AS1 survival were evaluated by using in situ hybridization and survival analysis. In addition, other experiments including RNA pull down analysis, RNA immunoprecipitation, luciferase reporter assays, and chromatin immunoprecipitation as well as validating assays conducted in vivo were applied to identify the target and regulatory mechanisms of IGBP1-AS1.ResultsSignificant down-regulation of IGBP1-AS1 was discovered in the cell lines and tissues of BC. With respect to its biological function, overexpression of IGBP1-AS1 had inhibitory effects on the invasion and proliferation of BC cells in vivo as well as in vitro. Analysis of the samples obtained from BC patients indicated a positive effect of IGBP1-AS1 on survival outcomes. LncRNA IGBP1-AS1/miR-24-1/ZIC3 axis as a loop can regulate the proliferation and invasion of BC cells.ConclusionsIGBP1-AS1 could have inhibitory impact on the invasion and proliferation of BC and may serve as a promising biomarker for BC. ]]> <![CDATA[The mitochondrial genome of UK (non-native) Dikerogammarus haemobaphes (Amphipoda: Gammaridae) informs upon Dikerogammarus evolution, invasions and associated microparasites]]> https://www.researchpad.co/article/Neb298a08-af67-41cf-a9ab-9d9ea094aff8

The amphipod Dikerogammarus haemobaphes is a high-risk carrier of parasites that impact wildlife in its non-native range. Studies using the mitochondrial genes, Cytochrome Oxidase Sub-Unit 1 (cox1) and small-subunit ribosomal RNA gene (16S), provide some nucleotide detail for understanding the evolution and phylogeography of this species. Despite this, the origins of the invasion remain unknown, as do the origins of its parasites. This study provides the full annotated mitochondrial genome (15,460 bp) of D. haemobaphes, consisting of 2 rRNAs, 24 tRNAs and 14 protein coding genes. Mitochondrial genes from the UK isolate are compared to existing data on NCBI and are used in a concatenated phylogenetic approach and identify D. haemobaphes as an early member of the Gammaridae (Amphipoda). Viral, bacterial, protistan and microsporidian parasites are present across the Gammaridae, including D. haemobaphes, suggesting the ancestor of the Gammaridae harboured related diseases, and that further screening of amphipods is likely to reveal further microparasite diversity. This correlation suggests that other gammarid invaders have the potential to harbour a range of microparasites. The mitochondrial genome of this species will act a resource to facilitate our understanding of geneflow, disease epidemiology and evolutionary history in this invasion-disease model.

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<![CDATA[ZEB1-AS1/miR-133a-3p/LPAR3/EGFR axis promotes the progression of thyroid cancer by regulating PI3K/AKT/mTOR pathway]]> https://www.researchpad.co/article/N9e3fe2d1-493a-4310-87a8-a55bba8e41e0

Background

Thyroid cancer (TC) is a member of common malignant tumors in endocrine system. To develop effective treatment, further comprehension of understanding molecular mechanism in TC is necessary. In this research, we attempted to search the underlying molecular mechanism in TC.

Methods

ZEB1-AS1 expression was analyzed via qRT-PCR analysis. CCK-8, colony formation, flow cytometry and TUNEL assays were used to evaluate TC cell growth. The interaction between miR-133a-3p and LPAR3, EGFR and ZEB1-AS1 was testified through using RNA pull down and luciferase reporter assays.

Results

LPAR3 and EGFR were expressed at high levels in TC tissues and cell lines. Besides, both LPAR3 and EGFR could promote TC cell growth. Later, miR-133a-3p was searched as an upstream gene of LPAR3 and EGFR, and LPAR3 could partially rescue the suppressive effect of miR-133a-3p overexpression on TC progression, whereas the co-transfection of LPAR3 and EGFR completely restored the inhibition. Next, ZEB1-AS1 was confirmed as a sponge of miR-133a-3p. ZEB1-AS1 has a negative correlation with miR-133a-3p and a positive association with LPAR3 and EGFR through ceRNA analysis. Importantly, ZEB1-AS1 boosted the proliferation and suppressed the apoptosis in TC cells. Through restoration assays, we discovered that ZEB1-AS1 regulated LPAR3 and EGFR expression to mediate TC cell proliferation and apoptosis by sponging miR-133a-3p. Further investigation also indicated the oncogenic role of ZEB1-AS1 by mediating PI3K/AKT/mTOR pathway.

Conclusions

ZEB1-AS1 could be an underlying biomarker in TC.

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<![CDATA[M2 bone marrow-derived macrophage-derived exosomes shuffle microRNA-21 to accelerate immune escape of glioma by modulating PEG3]]> https://www.researchpad.co/article/N6b3f5b0f-71b1-4414-a28d-433f3e9591ed

Background

Growing studies have focused on the role of microRNA-21 (miR-21) in glioma, thus our objective was to discuss the effect of M2 bone marrow-derived macrophage (BMDM)-derived exosomes (BMDM-Exos) shuffle miR-21 on biological functions of glioma cells by regulating paternally expressed gene 3 (PEG3).

Methods

Seventy-one cases of human glioma tissues and 30 cases of non-tumor normal brain tissues were collected and stored in liquid nitrogen. PEG3 and miR-21 expression in glioma tissues was tested. The fasting venous blood of glioma patients and healthy control was collected and centrifuged, and then the supernatant was stored at − 80 °C refrigerator. The contents of interferon (IFN)-γ and transforming growth factor-β1 (TGF-β1) in serum were tested by ELISA. Glioma cells and normal glial cells were cultured to screen the target cells for further in vitro experiments. BMDM-Exos was obtained by ultra-high speed centrifugation and then was identified. BMDM-Exos was co-cultured with U87 cells to detect the biological functions. The fasting venous blood of glioma patients was extracted and treated with ethylene diamine tetraacetic acid-K2 anti-freezing, and then CD8+T cells were isolated. CD8+T cells were co-cultured with U87 cells to detect the CD8+T proliferation, cell cytotoxic activity, U87 cell activity, as well as IFN-γ and TGF-β1 levels. Moreover, BALB/c-nu/nu mice was taken, and the human-nude mouse glioma orthotopic transplantation model was established with U87 cells, and then mice were grouped to test the trends in tumor growth. The brain of mice (fixed by 10% formaldehyde) was sliced to detect the expression of Ki67 and proliferating cell nuclear antigen (PCNA). The spleen of mice was taken to prepare single-cell suspension, and the percentage of T lymphocytes in spleen to CD8+T cells was detected.

Results

PEG3 expression was decreased and miR-21 expression was increased in glioma cells and tissues. Depleting miR-21 or restoring PEG3 suppressed growth, migration and invasion as well as accelerated apoptosis of glioma cells, also raised CD8+T proliferation, cell cytotoxic activity, and IFN-γ level as well as decreased U87 cell activity and TGF-β1 level. BMDM-Exos shuttle miR-21 promoted migration, proliferation and invasion as well as suppressed apoptosis of glioma cells by reducing PEG3. Exosomes enhanced the volume of tumor, Ki67 and PCNA expression, reduced the percentage of CD8+T cells in glioma mice.

Conclusion

BMDM-Exos shuffle miR-21 to facilitate invasion, proliferation and migration as well as inhibit apoptosis of glioma cells via inhibiting PEG3, furthermore, promoting immune escape of glioma cells.

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<![CDATA[FTX contributes to cell proliferation and migration in lung adenocarcinoma via targeting miR-335-5p/NUCB2 axis]]> https://www.researchpad.co/article/N3b2ba1ef-94eb-440d-93d4-010eabae1a86

Background

Extensive studies revealed that long non-coding RNAs (lncRNAs) could act as a regulator in tumors, including lung adenocarcinoma (LUAD). LncRNA FTX transcript, XIST regulator (FTX) has been reported to regulate the biological behaviors of some cancers. Nevertheless, its functional role and molecular mechanism remain obscure in LUAD. Our current study concentrates on exploring the biological function of FTX in LUAD.

Methods

RT-qPCR was used to test the expression of FTX, miR-335-5p or NUCB2 in LUAD cells. The effect of FTX on LUAD progression was investigated by colony formation, EdU, flow cytometry, TUNEL, transwell and western blot assays. The interaction between microRNA-335-5p (miR-335-5p) and FTX or nucleobindin 2 (NUCB2) was confirmed by luciferase reporter assay.

Results

RT-qPCR showed that FTX expression was up-regulated in LUAD cell lines. Loss-of-function assay indicated that FTX accelerated cell proliferation, migration and invasion, while inhibited cell apoptosis in LUAD. Besides, miR-335-5p, lowly expressed in LUAD cells, was discovered to be sponged by FTX. Subsequently, NUCB2 was identified as a target gene of miR-335-5p. Additionally, it was confirmed that NUCB2 functioned as an oncogene in LUAD. Rescue assays indicated that LUAD progression inhibited by FTX knockdown could be restored by NUCB2 up-regulation.

Conclusion

FTX played an oncogenic role in LUAD and contributed to cancer development via targeting miR-335-5p/NUCB2 axis.

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