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1.
ACS Nano ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31702890

RESUMO

The intricate features of many-body interactions and spin-orbit coupling play a significant role in numerous physcial phenomena. Particularly in two-dimensional transition metal dichalcogenides (2D-TMDs), excitonic dynamics are a key phenomenon that promises opportunities for diverse range of device applications. Here, we report the direct observation of a visible-range three-dimensional resonant exciton and its associated charged exciton in monolayer tungsten diselenide, as compared to monolayer molybdenum disulfide. A comprehensive experimental study that includes high-resolution TEM, Raman, high-resolution spectroscopic ellipsometry over a wide temperature range down to 4K, high-energy temperature and excitation power-dependent photoluminescence spectroscopy has been conducted. It is supported by first-principles calculations to unravel the influence of spin-orbit coupling in the formation of the resonant exciton and to identify its in-plane and out-of-plane features. Furthermore, we study the impact of temperature and thickness on the spin-orbit coupling strength in 2D-TMDs. This work is crucial in creating a platform in the fundamental understanding of high-energy resonant exciton in layered two-dimensional systems, and that such high-energy optoelectronic features make them an increasingly attractive candidate for novel electronic and optoelectronic applications particularly in the aspects of solar cells and light-emitting diodes via the manipulation of excitonic states.

2.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1097-1099, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703134

RESUMO

OBJECTIVE: To explore the genetic etiology of two unrelated patients with dyschromatosis symmetrica hereditaria. METHODS: Variant analysis of the ADAR gene was carried out by Sanger sequencing. RESULTS: Patient 1 was found to harbor a c.2633_2634delCT (p.Ser878fs) in exon 8 of the ADAR gene. The same variant was not found among 100 unrelated individuals. No pathogenic variant of the ADAR gene was found in patient 2. Functional prediction of the ADAR c.2633_2634delCT (p.Ser878fs) variant indicated it to be pathogenic by losing a catalytic structural domain. CONCLUSION: The c.2633_2634delCT (p.Ser878fs) variant of the ADAR gene probably underlies the pathogenesis of DSH in one of the patients.

3.
ACS Nano ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31693338

RESUMO

We present a combined experimental and theoretical study of monolayer vanadium ditelluride, VTe2, grown on highly oriented pyrolytic graphite by molecular-beam epitaxy. Using various in situ microscopic and spectroscopic techniques, including scanning tunneling microscopy/spectroscopy, synchrotron X-ray and angle-resolved photoemission, and X-ray absorption, together with theoretical analysis by density functional theory calculations, we demonstrate direct evidence of the metallic 1T phase and 3d1 electronic configuration in monolayer VTe2 that also features a (4 × 4) charge density wave order at low temperatures. In contrast to previous theoretical predictions, our element-specific characterization by X-ray magnetic circular dichroism rules out a ferromagnetic order intrinsic to the monolayer. Our findings provide essential knowledge necessary for understanding this interesting yet less explored metallic monolayer in the emerging family of van der Waals magnets.

4.
Mol Med Rep ; 20(6): 5145-5151, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31638258

RESUMO

To the best of our knowledge, the present study reported the case of the first Chinese patient with microcephaly­capillary malformation (MIC­CAP) syndrome caused by a novel compound heterozygous mutation in the STAMBP gene, which encodes STAM binding protein. The present study also provides a review of relevant previously published studies. A boy with MIC­CAP syndrome with developmental delay, intractable epilepsy and prominent dyskinesia was examined. A pathogenic mutation was identified by whole­exome sequencing, and the protein structure and function affected by this mutation were predicted using bioinformatics analysis. Finally, the clinical features of 16 other cases reported in previous studies were reviewed and compared. A novel compound heterozygous mutation of the STAMBP (c.1119­1G>T, c.968A>G) was identified in the present study and epilepsy was refractory, consistent with previously reported cases. The present study also highlighted the fact that STAMBP mutation­associated MIC­CAP often presents as intractable early­life epilepsy, which may lead to mortality.

5.
Cell Death Dis ; 10(10): 777, 2019 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-31611604

RESUMO

MET overactivation is one of the crucial reasons for tyrosine kinase inhibitor (TKI) resistance, but the mechanisms are not wholly clear. Here, COX2, TOPK, and MET expression were examined in EGFR-activating mutated NSCLC by immunohistochemical (IHC) analysis. The relationship between COX2, TOPK, and MET was explored in vitro and ex vivo. In addition, the inhibition of HCC827GR cell growth by combining COX2 inhibitor (celecoxib), TOPK inhibitor (pantoprazole), and gefitinib was verified ex vivo and in vivo. We found that COX2 and TOPK were highly expressed in EGFR-activating mutated NSCLC and the progression-free survival (PFS) of triple-positive (COX2, MET, and TOPK) patients was shorter than that of triple-negative patients. Then, we observed that the COX2-TXA2 signaling pathway modulated MET through AP-1, resulting in an inhibition of apoptosis in gefitinib-resistant cells. Moreover, we demonstrated that MET could phosphorylate TOPK at Tyr74 and then prevent apoptosis in gefitinib-resistant cells. In line with these findings, the combination of celecoxib, pantoprazole, and gefitinib could induce apoptosis in gefitinib-resistant cells and inhibit tumor growth ex vivo and in vivo. Our work reveals a novel COX2/MET/TOPK signaling axis that can prevent apoptosis in gefitinib-resistant cells and suggests that a triple combination of FDA-approved drugs would provide a low-cost and practical strategy to overcome gefitinib resistance.

6.
Ecotoxicol Environ Saf ; 184: 109593, 2019 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-31479760

RESUMO

Leaf vegetables have strong capabilities to take up cadmium (Cd) compared to other vegetable varieties. Until now, the differences in Cd uptake and accumulation by leaf vegetables from different families and genera and the related health risks were unknown. To remedy this, we studied 71 leaf vegetables (multiple genotypes within 17 categories of vegetables) in soil cultivation experiments (3 Cd treatment levels). Results showed that at 2.12 mg kg-1 Cd treatment, the dry weight of only five genotypic varieties from the families Brassicaceae and Asteraceae significantly decreased compared to the control, suggesting their weak Cd tolerances. Vegetables from the Brassicaceae, Asteraceae, Apiaceae, and Convolvulaceae families had stronger Cd absorption capabilities, whereas those from the Liliaceae and Amaranthaceae families had weaker ones. Cluster analysis found that the 17 vegetable categories could be divided into three groups: vegetables with high Cd accumulation capabilities were Lactuca sativa L.var. ramosa Hort. and Lactuca sativa var. longifoliaf. Lam. Vegetables with moderate Cd accumulation capabilities were bok choy, napa cabbage, choy sum, leaf mustard, Lactuca sativa L., Sonchus oleraceus L., celery, coriander, and water spinach. Vegetables with low Cd accumulation capabilities were cabbage, crown daisy, garlic chive, Allium ascalonicum, Gynura cusimbua, and edible amaranth. Estimated daily intake (EDI) and target hazard quotient (THQ) analysis results showed that 100% genotypes of vegetables from the Apiaceae and Convolvulaceae families had health risks; 100% genotypes of Lactuca sativa L., Sonchus oleraceus L., Lactuca sativa L. var. ramosa Hort., and Lactuca sativa var. longifoliaf. Lam from the Asteraceae family carried high risks. Of vegetables in the Brassicaceae family, 42.9% showed risks. Vegetables from the Amaranthaceae and Liliaceae families, Gynura cusimbua and crown daisy from the Asteraceae family, and cabbage from the Brassicaceae family all displayed relatively low risks (all 100%).

7.
Biomaterials ; 224: 119497, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31541935

RESUMO

In recent years, epigenetics has attracted great attentions in the field of biomedicine, which is used to denote the heritable changes in gene expression without any variation in DNA sequence, including DNA methylation, histone modification and so on. Inspired by it, a simple and versatile amino acids modification strategy is proposed in this paper to regulate the subcellular distribution of photosensitizer for plasma membrane targeted photodynamic therapy (PDT). Particularly, the plasma membrane anchoring ability and photo toxicity of the photosensitizer against different cell lines could be effectively manipulated at a single amino acid level. Systematic researches indicate that the number and variety of amino acids have a significant influence on the plasma membrane targeting effect of the photosensitizer. Furthermore, after self-assembling into nanoparticles, the obtained nano photosensitizers (NPs) also exhibit a good biocompatibility and plasma membrane targeting ability, which are conducive to enhancing the PDT therapeutic effect under light irradiation. Both in vitro and in vivo investigations confirm a robust tumor inhibition effect of NPs with a good biocompatibility. This epigenetics-inspired photosensitizer modification strategy would contribute to the development of structure-based drug design for tumor precision therapy.

8.
Am J Hypertens ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31504137

RESUMO

BACKGROUND: While sex differences characterize susceptibility and severity of idiopathic pulmonary arterial hypertension (IPAH), our understanding of the relationship between levels of gonadotropins and sex hormones in fertile women and the disease is limited. We aimed to investigate whether gonadotropin and sex hormone levels in women of reproductive age were associated with risk and mortality of IPAH. METHODS: We did a matched case-control study. Cases were reproductive female patients with idiopathic pulmonary arterial hypertension admitted in Shanghai Pulmonary Hospital (Tongji University School of Medicine, Shanghai, China) during 2008 to 2014. Healthy controls were matched on age and body mass index. We also did a prospective cohort study to assess the effects of hormone levels on mortality in IPAH fertile female patients. RESULTS: 164 cases and 133 controls were included. After adjustment for age and body mass index, the odds ratios of having IPAH for follicle stimulating hormone, testosterone, and progesterone as expressed on natural log scale were 1.51 (95%CI 1.06, 2.16), 0.42 (0.31-0.57), and 0.52(0.43-0.63), respectively. In the cohort study with a median follow up of 77-months, the hazard ratios for dying after adjustment for baseline characteristics and treatments among IPAH patients were 2.01 (95% CI: 1.22-3.30) and 0.78 (95% CI: 0.62-0.98) for follicle stimulating hormone and progesterone in natural log scale, respectively. CONCLUSIONS: In reproductive women with IPAH, high follicle stimulating hormone and low progesterone tended to be associated with high risk of IPAH and mortality among patients.

9.
Fertil Steril ; 2019 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-31551156

RESUMO

OBJECTIVE: To investigate the possible impact of local inflammation on granulosa cells (GCs) and follicular development in endometriosis patients. DESIGN: Prospective study with related paired design. SETTING: Reproductive medicine center. PATIENT(S): A total of 80 endometriosis patients and 104 controls, with cultured GCs collected from control participants younger than 35 years. INTERVENTION(S): Tumor necrosis factor-α (TNF-α) and nuclear factor κB (NF-κB) inhibitor. MAIN OUTCOME MEASURE(S): Intrafollicular concentrations of cytokines measured with ELISA, NF-κB binding levels with electrophoretic mobility shift assay (EMSA), and telomerase activity (TA) with quantitative-telomeric repeat amplification protocol (Q-TRAP) assay, and protein and mRNA expression with Western blot and polymerase chain reaction analyses, respectively. RESULT(S): Patients with endometriosis exhibited a statistically significantly lower antral follicle count (11.48 ± 8.11 vs. 15.68 ± 8.56), lower number of retrieved oocytes (8.28 ± 6.69 vs. 10.87 ± 6.26), and lower number of mature oocytes (6.67 ± 6.09 vs. 8.53 ± 5.69). The GCs from endometriosis patients showed higher NF-κB binding activity and increased expression of inhibitor of NF-κB kinase subunit ß (IKKß, 2.743-fold) and NF-κB inhibitor α (IκBα, 5.017-fold). Their NF-κB p65 expression was negatively associated with mature oocytes (bNF-κB' = -0.304, R2 = 0.195, R = 0.442) but positively associated with intrafollicular TNF-α (r = 0.37); TA showed a negative relationship with NF-κB binding levels (r = -0.667). Tumor necrosis factor-α induced expression of IκBα (5.408-fold) and NF-κB p65 (1.400-fold) but lowered human telomerase reverse transcriptase (hTERT) and TA levels (0.0009 vs. 0.5619) in cultured GCs. However, inhibiting NF-κB obviously increased hTERT expression (1.988-fold). CONCLUSION(S): Endometriosis showed activated NF-κB pathways in GCs, which might negatively affect TA and oocyte quality. Intrafollicular TNF-α might down-regulate TA and hTERT via NF-κB pathway, but further studies are required.

10.
Chem Commun (Camb) ; 55(81): 12172-12175, 2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31544179

RESUMO

Phthalimide-based "D-N-A" emitters o-AI-Cz, m-AI-Cz and p-AI-Cz showed TADF and RTP properties due to their small ΔEST in both film and crystalline states. In particular, o-AI-Cz exhibited an ultralong RTP with a lifetime of 602 ms in air and remarkable afterglow, which could allow it to be used as a security ink for application in anti-counterfeiting materials. Moreover, o-AI-Cz showed intense intramolecular interaction between the donor and the acceptor subunits, while p-AI-Cz could form regular hexagonal pores with a diameter of 13.171 Å in the solid state, which might result in their different RTP properties.

11.
Eur J Cancer ; 120: 10-19, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31446212

RESUMO

BACKGROUND: The role of epidermal growth factor receptor (EGFR) pathways in regulating telomerase is increasingly being recognised. We analysed the impact of rs2853669 single nucleotide polymorphism (SNP) on telomere parameters and its prognostic value for non-small cell lung cancer (NSCLC) with or without EGFR mutation. METHODS: The association of rs2853669 with telomerase reverse transcriptase (TERT) mRNA level and relative telomere length (RTL) was analysed using resected tumour samples from 250 NSCLC patients. We also investigated the patients' clinical outcomes with a median follow-up of 57 months (2-99 months). RESULTS: The rs2853669 T/C allele was significantly associated with lower TERT mRNA expression (versus C/C and versus T/T; p < 0.001 for both) and shorter RTL (versus C/C and versus T/T; p = 0.039 and 0.023) in patients without EGFR mutation. Such difference was not observed in their counterparts harbouring EGFR mutation. When considering the cohort as a whole, T/C allele was significantly associated with shortest overall survival compared with T/T or C/C allele (mean: 61.8, 80.9 and 88.7 months, plog-rank < 0.001) and disease-free survival (mean: 78.3, 87.9 and 91.5 months, plog-rank = 0.019). Stratification analyses showed that the negative prognostic effect of T/C on OS was constrained in patients without EGFR mutation. CONCLUSION: Our study revealed significant associations of a common SNP within TERT promoter region on telomere parameters and survival in NSCLC patients without EGFR mutation. The result may help providing instruction for therapeutic interventions targeting telomerase and evidence for investigation of TERT-EGFR interacting mechanism in telomere biology.

12.
Adv Mater ; 31(40): e1903779, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31423650

RESUMO

Among van der Waals layered ferromagnets, monolayer vanadium diselenide (VSe2 ) stands out due to its robust ferromagnetism. However, the exfoliation of monolayer VSe2 is challenging, not least because the monolayer flake is extremely unstable in air. Using an electrochemical exfoliation approach with organic cations as the intercalants, monolayer 1T-VSe2 flakes are successfully obtained from the bulk crystal at high yield. Thiol molecules are further introduced onto the VSe2 surface to passivate the exfoliated flakes, which improves the air stability of the flakes for subsequent characterizations. Room-temperature ferromagnetism is confirmed on the exfoliated 2D VSe2 flakes using a superconducting quantum interference device (SQUID), X-ray magnetic circular dichroism (XMCD), and magnetic force microscopy (MFM), where the monolayer flake displays the strongest ferromagnetic properties. Se vacancies, which can be ubiquitous in such materials, also contribute to the ferromagnetism of VSe2 , although density functional theory (DFT) calculations show that such effect can be minimized by physisorbed oxygen molecules or covalently bound thiol molecules.

13.
Chin Med J (Engl) ; 132(18): 2168-2176, 2019 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-31461731

RESUMO

BACKGROUND: Anastomotic leakage is a serious surgical complication in rectal cancer; however, effective evaluation methods for predicting anastomotic leakage individual risk in patients are not currently available. This study aimed to develop a method to evaluate the risk of leakage during surgery. METHODS: The 163 patients with rectal cancer, who had undergone anterior resection and low-ligation procedures for Doppler sonographic hemodynamic measurement from April 2011 to January 2015 in Peking University Cancer Hospital, were prospectively recruited. A predictive model was constructed based on the associations between anastomotic leakage and alterations in the anastomotic blood supply in the patients, using both univariate and multivariate statistical analyses, as well as diagnostic methodology evaluation, including Chi-square test, logistic regression model, and receiver operating characteristic curve. RESULTS: The overall anastomotic leakage incidence was 9.2% (15/163). Doppler hemodynamic parameters whose reduction was significantly associated with anastomotic leakage were peak systolic velocity, pulsatility index, and resistance index. The areas under the receiver operating characteristic curve of residual rates of peak systolic velocity, pulsatility index, and resistance index in predicting anastomotic leakage were 0.703 (95% confidence interval [CI]: 0.552-0.854), 0.729 (95% CI: 0.579-0.879), and 0.689 (95% CI: 0.522-0.856), respectively. The predictive model revealed that the patients with severely reduced blood-flow signal exhibited a significantly higher incidence rate of anastomotic leakage than those with sufficient blood supply (19.6% vs. 3.7%, P = 0.003), particularly the patients with low rectal cancer (25.9% vs. 3.9%, P = 0.007) and those receiving neoadjuvant chemoradiotherapy (32.1% vs. 3.7%, P = 0.001), independent of prophylactic ileostoma. Multivariate analysis revealed that insufficient blood supply of the anastomotic bowel was an independent risk factor for anastomotic leakage (odds ratio: 10.37, 95% CI: 2.703-42.735, P = 0.001). CONCLUSION: Based on this explorative study, Doppler sonographic hemodynamic measurement of the anastomotic bowel presented potential value in predicting anastomotic leakage.

14.
Behav Sleep Med ; : 1-15, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31426678

RESUMO

Objective/Background: Subjective methods are often employed for sleep assessment due to their ease of use, but the results may not concur with objective findings. This discrepancy may be present in schizophrenia; however, limited data are available. We performed a secondary analysis to evaluate the agreement between 1-week actigraphy and sleep diary-derived parameters and factors that contribute to subjective-objective sleep discrepancy. Participants: 66 outpatients with schizophrenia (mean age = 44.08 years; 45.45% males). Methods: Agreement between subjective-objective parameters was assessed using two-way repeated measures ANOVA, Pearson's correlation, and Bland-Altman plot. The magnitude of discrepancy was quantified using Cohen's d. Pearson's correlation was used to determine the significant factors of subjective-objective sleep discrepancy. Benjamini-Hochberg adjustment was performed to account for multiple testing. Results: On average, sleep diaries overestimated sleep onset latency by 20.45 min, total sleep time by 37.63 min, and sleep efficiency by 4.29%, but underestimated wake after sleep onset by 33.28 min. Cohen's d ranged between 0.61 and 1.41. Subjective-objective discrepancies were significantly associated with marital and employment status, self-reported sleep disturbance, delayed sleep-wake phase disorder, chronotype, and psychosocial functioning (r = 0.32-0.44; Benjamini-Hochberg corrected p < .05). Conclusions: Our findings show that differences between subjective and objective measurements of sleep are present in schizophrenia. Although actigraphy is not a standard procedure for sleep disturbance in schizophrenia, clinical judgment should be used if patients are suspected to have overestimated their sleep difficulties. Further studies should examine whether feedback based on actigraphy can benefit patients with schizophrenia and comorbid sleep disturbances.

15.
Cell Death Dis ; 10(8): 583, 2019 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-31378785

RESUMO

ULK1, the upper-most protein of the ULK1 complex, is emerging as a crucial node in autophagy induction. However, the regulation of ULK1 is not fully understood. In this study, we identified TOPK (T-LAK cell-originated protein kinase), an oncokinase, as a novel upstream kinase to phosphorylate ULK1. We found that TOPK could directly bind with and phosphorylate ULK1 at Ser469, Ser495, and Ser533. The phosphorylation of ULK1 at Ser469, Ser495, and Ser533 by TOPK decreased the activity and stability of ULK1. In addition, we want to examine the initiation of autophagy because the reduction activity of ULK1 reduces the occurrence of autophagy. We demonstrated that TOPK could inhibit the initiation and progression of autophagy in glioma cells. Furthermore, TOPK inhibition increased the sensitivity of glioma cells to temozolomide (TMZ). This discovery provides insight into the problem of TMZ-resistance in GBM treatment.

16.
Cancer Lett ; 462: 43-50, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31381961

RESUMO

While research into the role of cathepsins has been progressing at an exponential pace over the years, research into their respective isoform proteins has been less frenetic. In view of the functional and biological potential of such protein isoforms in model systems for cancer during their initial discovery, much later they have offered a new direction in the field of cathepsin basic and applied research. Consequently, the analysis of such isoforms has laid strong foundations in revealing other important regulatory aspects of the cathepsin proteins in general. In this review article, we address these key aspects of cathepsin isoform proteins, with particular emphasis on how they have shaped what is now known in the context of nuclear cathepsin localization and what potential these hold as nuclear-based therapeutic targets in cancer.

17.
Cell Death Dis ; 10(8): 597, 2019 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-31395857

RESUMO

Human adipose-derived stem cells (hADSCs) are increasingly presumed to be a prospective stem cell source for cell replacement therapy in various degenerative and/or traumatic diseases. The potential of trans-differentiating hADSCs into motor neuron cells indisputably provides an alternative way for spinal cord injury (SCI) treatment. In the present study, a stepwise and efficient hADSC trans-differentiation protocol with retinoic acid (RA), sonic hedgehog (SHH), and neurotrophic factors were developed. With this protocol hADSCs could be converted into electrophysiologically active motoneuron-like cells (hADSC-MNs), which expressed both a cohort of pan neuronal markers and motor neuron specific markers. Moreover, after being primed for neuronal differentiation with RA/SHH, hADSCs were transplanted into SCI mouse model and they survived, migrated, and integrated into injured site and led to partial functional recovery of SCI mice. When ablating the transplanted hADSC-MNs harboring HSV-TK-mCherry overexpression system with antivirial Ganciclovir (GCV), functional relapse was detected by motor-evoked potential (MEP) and BMS assays, implying that transplanted hADSC-MNs participated in rebuilding the neural circuits, which was further confirmed by retrograde neuronal tracing system (WGA). GFP-labeled hADSC-MNs were subjected to whole-cell patch-clamp recording in acute spinal cord slice preparation and both action potentials and synaptic activities were recorded, which further confirmed that those pre-conditioned hADSCs indeed became functionally active neurons in vivo. As well, transplanted hADSC-MNs largely prevented the formation of injury-induced cavities and exerted obvious immune-suppression effect as revealed by preventing astrocyte reactivation and favoring the secretion of a spectrum of anti-inflammatory cytokines and chemokines. Our work suggests that hADSCs can be readily transformed into MNs in vitro, and stay viable in spinal cord of the SCI mouse and exert multi-therapeutic effects by rebuilding the broken circuitry and optimizing the microenvironment through immunosuppression.

18.
PLoS One ; 14(8): e0220118, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31369587

RESUMO

BACKGROUND: Circular RNAs (circRNAs) have been shown to interact with microRNAs (miRNA) as competitive endogenous RNAs (ceRNAs) to regulate target gene expression and participate in tumorigenesis. However, the role of circRNA-mediated ceRNAs in bladder cancer (BC) remains unknown. Accordingly, the aim of this study was to elucidate the regulatory mechanisms in BC based on construction of the ceRNA network. METHODS: The RNA expression profiles were obtained from public datasets in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) database, and were used to establish a circRNA-miRNA-mRNA network. The interactions among proteins were analyzed using the STRING database and hubgenes were extracted using the cytoHubba application. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses of differentially expressed mRNAs in BC and normal tissue samples were performed to determine the functions of the intersecting mRNAs. RESULTS: A total of 27 circRNAs, 76 miRNAs, and 4744 mRNAs were found to be differentially expressed between BC and normal tissues. The circRNA-miRNA-mRNA ceRNA network was established based on 21 circRNAs, 14 miRNAs, and 150 mRNAs differentially expressed in BC. We also established a protein-protein interaction network and identified 10 hubgenes, which were used to construct circRNA-miRNA-hubgene regulatory modules. The most enriched biological process GO term was strand displacement (P<0.05), and the homologous recombination and Fanconi anemia pathways were significantly enriched (P<0.05) for the differentially expressed genes in BC. CONCLUSIONS: We screened several dysregulated circRNAs and established a circRNA-associated ceRNA network by bioinformatics analysis. The identified ceRNAs are likely critical in the pathogenesis of BC and may serve as future therapeutic biomarkers.

20.
Sci Rep ; 9(1): 9820, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31285444

RESUMO

MicroRNA-212-3p inhibits several human cancers but its effects on hepatocellular carcinoma (HCC) remain unclear. In this study, we show that miR-212-3p is down-regulated in HCC cell lines and tissues, and correlates with vascular invasion (p = 0.001), and the absence of capsule formation (p = 0.009). We found that miR-212-3p influenced the epithelial to mesenchymal transition (EMT) of HCCLM3 and Huh7 cells. Mechanistically, miR-212-3p repressed cell invasion through the suppression of connective tissue growth factor (CTGF). We therefore validate the anti-HCC effects of miR-212-3p through its ability to suppress CTGF and subsequent EMT.

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