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1.
Mol Ther Nucleic Acids ; 18: 24-33, 2019 Jul 29.
Artigo em Inglês | MEDLINE | ID: mdl-31479922

RESUMO

The aim of this study is to explore the roles of circular RNA (circRNA) Cdr1as on cisplatin resistance in ovarian cancer and explore the underlying mechanisms. We investigated the expression of circRNAs in five paired cisplatin-sensitive and cisplatin-resistant tissues of ovarian cancer by microarray analysis. The quantitative real-time PCR analysis was to investigate the expression pattern of Cdr1as in cisplatin-resistant ovarian cancer patient tissues and cell lines. Then, the effects of Cdr1as on cisplatin resistance, cell proliferation, and apoptosis were assessed in ovarian cancer cells. In this study, Cdr1as was observed to be downregulated in cisplatin-resistant patient tissues and cell lines. Overexpression of Cdr1as inhibited cell proliferation and promoted the cisplatin-induced cell apoptosis in ovarian cancer cells. Then we demonstrated that repressed Cdr1as promoted the miR-1270 expression, and miR-1270 could bind to the predicted binding site of Cdr1as. Furthermore, we found that miR-1270 displayed its role via modulating the Suppressor of Cancer Cell Invasion (SCAI) expression. Importantly, we demonstrated that Cdr1as was downregulated in serum exosomes from cisplatin-resistant patients. In summary, our study demonstrated that Cdr1as sensitizes ovarian cancer to cisplatin by regulating the miR-1270/SCAI signaling pathway.

2.
J Cell Biochem ; 2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31464068

RESUMO

This manuscript aimed to investigate linc-PINT's role as a tumor suppressor and its downstream microRNAs (miRNAs) in esophageal cancer. Log-rank, Cox, and nomogram were used for survival analysis. Quantitative real-time polymerase chain reaction was used to evaluate the expression. Cell counting kit-8 was used for proliferation tests. As for in vivo experiments, low expression of linc-PINT was associated with better prognosis; besides, the nomogram indicated that linc-PINT, miR-543, and miR-576-5p served well in predicting the survival rate. As for the in vitro experiments, linc-PINT could directly regulate miR-543 and miR-576-5p to inhibit the proliferation of Eca-109 cell line. In conclusion, linc-PINT-miR-543/miR-576-5p pathway could predict the prognosis and provide novel therapeutic targets for esophageal cancer.

3.
Neurochem Res ; 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31410708

RESUMO

Tripartite motif 32 (TRIM32) is a member of TRIM family that plays a potential role in neural regeneration. However, the biological function of TRIM32 in cerebral ischemia reperfusion injury has not been investigated. In the present study, we evaluated the expression level of TRIM32 in hippocampal neurons following oxygen-glucose deprivation/reperfusion (OGD/R). The results showed that TRIM32 expression was significantly elevated in hippocampal neurons subjected to OGD/R as compared to the neurons cultured in the normoxia condition. To further evaluate the role of TRIM32, hippocampal neurons were transfected with TRIM32 small interfering RNA (si-TRIM32) to knock down TRIM32. We found that knockdown of TRIM32 improved cell viability of OGD/R-stimulated hippocampal neurons. Generation of reactive oxygen species was decreased, while contents of superoxide dismutase and glutathione peroxidase were increased after si-TRIM32 transfection. Knockdown of TRIM32 suppressed cell apoptosis, as proved by the increased bcl-2 expression along with decreased bax expression and caspase-3 activity. We also found that TRIM32 knockdown enhanced OGD/R-induced activation of Nrf2 signaling pathway in hippocampal neurons. Furthermore, siRNA-Nrf2 was transfected to knock down Nrf2. SiRNA-Nrf2 transfection reversed the protective effects of TRIM32 knockdown on neurons. These data suggested that knockdown of TRIM32 protected hippocampal neurons from OGD/R-induced oxidative injury through activating Nrf2 signaling pathway.

4.
Mol Genet Genomic Med ; 7(8): e835, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31270966

RESUMO

BACKGROUND: Atrial fibrillation (AF) is one of the common arrhythmia in clinics. Its incidence is high among the elderly. This study aimed to identify a possible connection between ion channel-related gene polymorphisms and the risk of AF. METHODS: A total of 381 patients with coronary heart disease were recruited. Based on complete cardiac examination, the patients were divided into two subgroups: 185 patients with AF and 196 patients without AF. An association analysis was performed using 13 genotyped SNPs. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated by conditional logistic regression. RESULTS: In our research, we found that KCNE2 rs8134775 was associated with a decreased AF risk in the allele model (OR = 0.70; 95% CI: 0.50-0.97; p = 0.034). Genetic model analysis shown that the minor allele T of GJA5 rs35594137 was associated with a decreased AF risk under the recessive model (OR = 0.40; 95% CI: 0.19-0.86; p = 0.018) and the minor allele G of KCNJ2 rs8079702 was associated with an increased AF risk in the recessive model (OR = 2.31; 95% CI: 1.20-4.42; p = 0.012). CONCLUSIONS: Our results suggest that KCNE2, KCNJ2, and GJA5 influence the development of AF.

5.
ISME J ; 2019 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227815

RESUMO

Picocyanobacteria make up half of the ocean's primary production, and they are subjected to frequent viral infection. Viral lysis of picocyanobacteria is a major driving force converting biologically fixed carbon into dissolved organic carbon (DOC). Viral-induced dissolved organic matter (vDOM) released from picocyanobacteria provides complex organic matter to bacterioplankton in the marine ecosystem. In order to understand how picocyanobacterial vDOM are transformed by bacteria and the impact of this process on bacterial community structure, viral lysate of picocyanobacteria was incubated with coastal seawater for 90 days. The transformation of vDOM was analyzed by ultrahigh-resolution mass spectrometry and the shift of bacterial populations analyzed using high-throughput sequencing technology. Addition of picocyanobacterial vDOM introduced abundant nitrogen components into the coastal water, which were largely degraded during the 90 days' incubation period. However, some DOM signatures were accumulated and the total assigned formulae number increased over time. In contrast to the control (no addition of vDOM), bacterial community enriched with vDOM changed markedly with increased biodiversity indices. The network analysis showed that key bacterial species formed complex relationship with vDOM components, suggesting the potential correspondence between bacterial populations and DOM molecules. We demonstrate that coastal bacterioplankton are able to quickly utilize and transform lysis products of picocyanobacteria, meanwhile, bacterial community varies with changing chemodiverisity of DOM. vDOM released from picocyanobacteria generated a complex labile DOM pool, which was converted to a rather stable DOM pool after microbial processing in the time frame of days to weeks.

6.
Fish Shellfish Immunol ; 92: 133-140, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31173860

RESUMO

Infectious spleen and kidney necrosis virus (ISKNV) cause a high mortality disease which lead to significant economic loss on mandarin fish in China. There is no effective drug or vaccine against this fatal disease at present. Meanwhile, many drugs and vaccines had no effect in many cases account of several impenetrable barriers (cell, skin and gastrointestinal tract). Here we reported an immersion subunit vaccine system (SWCNTs-MCP) encoding MCP gene of ISKNV based on single-walled carbon nanotubes (SWCNTs). To evaluate its efficacy against ISKNV, we found a stronger and longer duration immune response (serum antibody production, enzyme activities and immune-related genes expression) can be induced in fish vaccinated with SWCNTs-MCP in comparison with those vaccinated with MCP alone. Importantly, SWCNTs can increase the immune protective effect of naked subunit vaccine by ca. 23.8%. Thereby, this study demonstrates that SWCNTs as a promising carrier for subunit vaccine might be used to vaccinate large-scale juvenile mandarin fish by bath administration approach.

7.
Huan Jing Ke Xue ; 40(4): 1751-1759, 2019 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-31087916

RESUMO

Dissolved organic matter (DOM) is a characteristic index of water quality, and reflects many factors, such as the economic development and protection policies of watershed. In this study, surface water samples were collected from four watersheds with different levels of urbanization in Ningbo. The DOM was analyzed using an excitation-emission matrix combined with parallel factor analysis (EEM-PARAFAC) to explore the relationship between land-use and DOM. The results show that the urbanization level affected both the amount and the composition of the DOM in the studied watersheds. The concentrations of DOM evaluated by dissolved organic carbon (DOC) in urban areas (DOC=3.18 mg·L-1) and an urban-rural combined area (DOC=7.45 mg·L-1) were much higher than those in rural areas with low urbanization (DOC between 2.16 and 2.62 mg·L-1, ANOVA, P<0.001). A total of seven PARAFAC components were identified in the studied watersheds, mainly including humic-like and protein-like substances. In the highly urbanized area, DOM was mainly composed of humic-like substances, with a proportion of 61.3%. However, the water samples from the urban-rural combined area exhibited a high proportion (59.4%) of protein-like substances, indicating a strong influence of sewage and industrial discharge. In contrast, although the DOM amounts in rural areas were relatively low, the proportions of humus-like substances were high, ranging from 63.6% to 65.7%. Agricultural non-point sources were the main contributor to DOM in these areas. Moreover, the results suggest that the urbanization process could intensify the damage to the surface waters. At the initial stage of urbanization (i.e., urban-rural combined area), contaminants are mainly discharged from sewage and industrial sources; when urbanization reaches a certain level, e.g., with a well-constructed sewage collection system, water contaminants originate more from surface runoff rather than sewage. The results of this study suggest that the EEM-PARAFAC technique can provide semi-quantitative source tracking of surface water, as well as an inexpensive and effective tool for policy makers to overcome the insensitivity of general water quality indices.

8.
Biosci Rep ; 39(6)2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31092699

RESUMO

Introduction: The treatment strategy for low-grade gliomas (LGGs) is still controversial, and there are no standardized criteria to predict the prognosis of patients with LGGs. Magnetic resonance imaging (MRI) is a routine test for preoperative diagnosis for LGG and can reflect the destructive features for the tumor. In the present study, we aimed to explore the relationship between the MRI features and prognosis in patients with LGG.Methods: Clinical data of 80 patients with pathologically proved LGGs between January 2010 and December 2016 were analyzed retrospectively. MRI features were classified as contrast enhancement pattern (focal enhancement, diffuse enhancement and ring-like enhancement), necrosis and cysts based on the preoperative MR images. Kaplan-Meier method and multivariate analysis were performed on the data by SPSS software to explore the prognostic significance of MRI features.Results: Patients with cystic LGG had a significantly longer 5-year progression-free survival (PFS) than that with no cyst (90.9 ± 8.7 vs 65.7 ± 9.1%, P=0.045). Multivariate analysis further verified cyst as an independent prognosis factor for PFS (P=0.027, hazard ratio [HR] = 0.084). Additionally, patients with ring-like enhancement exhibited significantly longer 5-year PFS time in the Kaplan-Meier survival curves (100 vs 67.2 ± 7.7%, P=0.049). There was no significant difference in PFS and overall survival (OS) between patients with or without necrosis.Conclusion: Our study suggests that cyst formation and ring-like enhancement on preoperative MR images can be useful to predict a favorable prognosis in patients with LGGs.

9.
Chem Commun (Camb) ; 55(38): 5487-5490, 2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31017141

RESUMO

Application of an oxidative amination reagent (di-tert-butyldiaziridinone) to the Ru3(CO)12-catalyzed ortho-selective CAr-H amination reaction is described. This strategy shows good functional group compatibility with various phenyl-substituted N-heterocycles, including biologically active substrates, thus providing synthetic potential for this methodology. Mechanistic studies showed that the reaction process involves an octahedral ruthenium species, and the carbon monoxide ligand plays a crucial role in the C-H activation.

10.
Biosci Rep ; 39(5)2019 May 31.
Artigo em Inglês | MEDLINE | ID: mdl-30988073

RESUMO

Triple-negative breast cancer (TNBC) accounts for approximately 15% of all breast cancer cases. TNBC is highly aggressive and associated with poor prognosis. The present study aimed to compare gene expression between TNBC patients with pathological complete response (pCR) and those with not complete response (nCR) to neoadjuvant chemotherapy. Microarray data of 16 TNBC patients received neoadjuvant chemotherapy were identified from the Gene Expression Omnibus database and 10 patients of them had pCR. We found that 250 coding genes and 155 long noncoding RNAs (lncRNAs) were statistically differentially expressed between patients with pCR and nCR. Receiver operator characteristic curve and area under the curve (AUC) were calculated to assess predictive value of differentially expressed genes. A gene signature of three coding genes and two lncRNA was developed: 2.318*TCF3 + 7.349*CREB1 + 0.891*CEP44 + 0.091*NR_023392.1 + 1.424*NR_048561.1 - 106.682. The gene signature was further validated and had an AUC = 0.829. In summary, we profiled gene expression in pCR patients and developed a gene signature, which was effective to predict pCR among TNBC patients received neoadjuvant chemotherapy.

11.
Dalton Trans ; 48(19): 6484-6491, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30994131

RESUMO

Reasonably designing Z-scheme photocatalysts has been deemed to be an ideal and prospective way to develop new and highly efficient photocatalytic materials for removing environmental pollutants. Herein, a new type of AgxH3-xPMo12O40/Ag nanorods/g-C3N4 1D/2D Z-scheme photocatalyst (abbr. APM/C3N4) was fabricated by a simple self-assembly procedure. Transmission electron microscopy (TEM) images revealed that the 1D silver polyoxometalate (POM) nanorods loaded with Ag nanoparticles (AgxH3-xPMo12O40/Ag = APM) were well dispersed on the plicated 2D g-C3N4 nanosheets. Photocatalytic experiments demonstrated that these composite catalysts exhibited an excellent and durable photocatalytic performance for the degradation of methyl orange (MO) and tetracycline (TC) and the photoreduction of Cr(vi) under visible light, which was significantly higher than that of the individual components and most of the previous reported materials. The photocatalytic mechanism suggests that superoxide and holes are the main active species in MO photodegradation, demonstrating its Z-scheme photocatalytic process. The synergistic effects of the enhanced light absorption, unique 1D/2D hybrid heterojunction structure, good and efficient interfacial contact and Z-scheme process endowed the as-prepared APM/C3N4 composites with excellent performance. This study may provide a new comprehension into the design of polyoxometalate-based Z-scheme hybrid materials for photocatalytic applications in the removal of organic and inorganic pollutants from wastewater.

12.
PLoS One ; 14(3): e0211964, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30840656

RESUMO

Urban change (urbanization) has dominated land change science for several decades. However, few studies have focused on what many scholars call the urban densification process (i.e., urban intensity expansion) despite its importance to both planning and subsequent impacts to the environment and local economies. This paper documents past urban densification patterns and uses this information to predict future densification trends in southeastern Wisconsin (SEWI) by using a rich dataset from the United States and by adapting the well-known Land Transformation Model (LTM) for this purpose. Urban densification is a significant and progressive process that often accompanies urbanization more generally. The increasing proportion of lower density areas, rather than higher density areas, was the main characteristic of the urban densification in SEWI from 2001 to 2011. We believe that improving urban land use efficiency to maintain rational densification are effective means toward a sustainable urban landscape. Multiple goodness-of-fit metrics demonstrated that the reconfigured LTM performed relatively well to simulate urban densification patterns in 2006 and 2011, enabling us to forecast densification to 2016 and 2021. The predicted future urban densification patterns are likely to be characterized by higher densities continue to increase at the expense of lower densities. We argue that detailed categories of urban density and specific relevant predictor variables are indispensable for densification prediction. Our study provides researchers working in land change science with important insights into urban densification process modeling. The outcome of this model can help planners to identify the current trajectory of urban development, enabling them to take informed action to promote planning objectives, which could benefit sustainable urbanization definitely.

13.
Int J Infect Dis ; 83: 12-19, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30904675

RESUMO

Follicular CXCR5+CD8+ T cells have antiviral effects in chronic virus infection, but the roles of these cells during dengue virus 2 (DENV2) infection remain poorly understood. OBJECTIVE: This study was conducted to analyzed in detail the dynamic changes and functional properties of circulating follicular CXCR5+CD8+ T cells to explore their effects on DENV2 infection. METHODS: Circulating follicular CXCR5+CD8+ T cells and cytokines were analyzed by flow cytometry in DENV2 patients at difference days after DENV2 infection. CD8+ T cells were isolated and purified from DENV2 patients, then were stimulated with NS1 peptides and TCR stimulant. After cultivation, multiple parameters were tested. RESULTS: (1) CXCR5+CD8+ T cells emerged after DENV2 infection, with high PD-1 expression, and were correlated with the reduction in DENV2 RNA viral loads. (2) PD-1+CXCR5+CD8+ T cells were negatively associated with disease progression. (3) Serum IFN-γ, IL-6 and IL-10 levels were increased late in the course of DENV2 infection. (4) CXCR5+CD8+ T cells from DENV2 patients exhibited increased cytotoxicity and IFN-γ and IL-10 secretion. CONCLUSION: CXCR5+CD8+ T cells could play a protective role in dengue pathogenesis and may be a novel strategy for controlling DENV2 infection and vaccine development.


Assuntos
Linfócitos T CD8-Positivos/imunologia , Dengue/imunologia , Receptores CXCR5/análise , Adulto , Citocinas/sangue , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
15.
Cancer Cell Int ; 18: 195, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30524203

RESUMO

Background: MicroRNAs play crucial roles in tumorigenesis and tumor progression. miR-770 has been reported to be downregulated in several cancers and affects cancer cell proliferation, apoptosis, metastasis and drug resistance. However, the role and underlying molecular mechanism of miR-770 in human glioma remain unknown and need to be further elucidated. Methods: The expression of miR-770 in glioma tissues and cell lines was measured by quantitative real-time PCR (qRT-PCR) to explore the association of miR-770 expression with clinicopathological characteristics. The expression of CDK8 was detected by qRT-PCR and Western blotting in glioma tissues. A target prediction program and a dual-luciferase reporter assay were used to confirm that CDK8 is a target gene of miR-770. MTT and cell counting assays were used to assess the effect of miR-770 on glioma cell proliferation. The cell cycle distribution and apoptosis were examined by flow cytometry. CDK8 siRNA and overexpression were used to further confirm the function of the target gene. Results: We demonstrated that miR-770 expression was downregulated in human glioma tissues and cell lines. The overexpression of miR-770 inhibited glioma cell proliferation and cell cycle G1-S transition and induced apoptosis. The inhibition of miR-770 facilitated cell proliferation and G1-S transition and suppressed apoptosis. miR-770 expression was inversely correlated with CDK8 expression in glioma tissues. CDK8 was confirmed to be a direct target of miR-770 by using a luciferase reporter assay. The overexpression of miR-770 decreased CDK8 expression at both the mRNA and protein levels, and the suppression of miR-770 increased CDK8 expression. Importantly, CDK8 silencing recapitulated the cellular and molecular effects observed upon miR-770 overexpression, and CDK8 overexpression eliminated the effects of miR-770 overexpression on glioma cells. Moreover, both exogenous expression of miR-770 and silencing of CDK8 resulted in suppression of the Wnt/ß-catenin signaling pathway. Conclusions: Our study demonstrates that miR-770 inhibits glioma cell proliferation and G1-S transition and induces apoptosis through suppression of the Wnt/ß-catenin signaling pathway by targeting CDK8. These findings suggest that miR-770 plays a significant role in glioma progression and serves as a potential therapeutic target for glioma.

16.
Vaccine ; 36(42): 6334-6344, 2018 10 08.
Artigo em Inglês | MEDLINE | ID: mdl-30201303

RESUMO

As a successful prevention strategy for controlling the highly contagious and pathogenic disease of spring viremia of carp (SVC), DNA vaccines reported in recent years could trigger protective responses against SVC with the means of injection. However, there remains many concerns and uncertainties related to DNA vaccination as well as injection is labor intensive, costly and not suitable to vaccinate large numbers of fish. Therefore, more efficient and safe prophylactic measures should be urgently investigated. In this research, single-walled carbon nanotubes (SWCNTs) as the candidate SWCNTs-pET32a-G subunit vaccine carrier were administrated via bath (1, 5, 10, 20, 40 mg L-1) or injection (1, 4, 8, 12, 20 µg) in common carp juvenile, and the different immune treatments to induce immunoprotective effect were analyzed. The results showed that SWCNTs-pET32a-G could enter fish body after immersion for 10 h, furthermore, compared to control groups, antibody levels, the non-specific immune parameters (complement activity, superoxide dismutase activity and alkaline phosphatase activity), and immune-related genes (especially the TNF-α and IFNg2b) in vaccinated groups were significantly enhanced in fish immunized with SWCNTs-subunit vaccine. In addition, as a promising carrier, SWCNTs can increase the immune protective effect of naked subunit vaccine by ca. 16% in bath immunization group and by ca. 23% in injection group. This study suggests that SWCNTs-vaccine may represent a potentially efficient immersion vaccine against viral pathogens of fish in the future.

17.
PLoS One ; 13(8): e0202269, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30125322

RESUMO

Zoledronic acid (ZA) exerts complex influence on bone by suppressing bone resorption, mostly due to the direct osteoclasts inhibition and uncertain influence on osteoblasts. Vitamin K2 (VK2, Menaquinone-4) as an anabolic agent stimulates bone formation via anti-apoptosis in osteoblasts and mild osteoclasts inhibition. Based on these knowledge, the therapeutic effect of the combined or sequential therapy of VK2 and ZA depends on the influence on the osteoblasts, since both cases exert similar inhibitory effect on osteoclasts. In a series of in vitro studies, we confirmed the protective effect of VK2 in osteoblasts culture, especially when followed by exposure to ZA, and the proliferation and mineralization inhibition induced by ZA towards osteoblasts. For mechanism study, expression of bcl-2/bax, Runx2 and Sost in cells were examined. For in vivo studies, an osteoporosis animal model was established in rats via ovariectomy (OVX) and subjected to sequential treatment, namely VK2 followed by ZA. Bone mineral density (BMD) was measured by Dual energy X-ray absorptionmetry (DEXA), morphology and mechanical parameters by micro-computed tomography (micro-CT), mechanical strength by an electro-hydraulic fatigue-testing machine. The bone calcium, hydroxyproline content, blood lipids were evaluated using microplate technique, and the bone surface turnover was evaluated using the fluorescence in corporation method. It was found that VK2 pretreatment partially prevented the inhibition of bone formation caused by ZA, which was reflected by indices like BMD, bone calcium content and bone strength. The underling mechanisms for protection of VK2 pretreatment, mainly demonstrated via in vitro studies, included inhibiting apoptosis and depressing Sost expression in osteoblasts, which in turn improved the osteoporosis therapeutic effects of ZA. These findings suggested that pretreatment with VK2 before ZA therapy might serve a new long-term therapy protocol for osteoporosis.

18.
J Am Chem Soc ; 140(34): 10639-10643, 2018 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-30094995

RESUMO

Here we present a modular method for manufacturing large-sized nanodiscs using DNA-origami barrels as scaffolding corrals. Large-sized nanodiscs can be produced by first decorating the inside of DNA barrels with small lipid-bilayer nanodiscs, which open up when adding extra lipid to form large nanodiscs of diameters ∼45 or ∼70 nm as prescribed by the enclosing barrel dimension. Densely packed membrane protein arrays are then reconstituted within these large nanodiscs for potential structure determination. Furthermore, we demonstrate the potential of these nanodiscs as model membranes to study poliovirus entry.

19.
Cancer Res Treat ; 2018 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-30025446

RESUMO

Purpose: Although the interferon α (IFNα) signaling and the paired-like homeodomain transcription factor 2 (PITX2) have both been implicated in the progression of breast cancer (BCa), it remains obscure whether these two pathways act in a coordinated manner. We therefore aimed to elucidate the expression and function of PITX2 during the pathogenesis of endocrine resistance in BCa. Materials and methods: PITX2 expression was assessed in BCa tissues using quantitative RT-PCR (RT-qPCR) and immunohistochemistry and in experimentally induced letrozole-resistant BCa cells using RT-qPCR and immunoblotting. Effects of PITX2 deregulation on BCa progression was determined by assessing MTT, apoptosis and xenograft model. Finally, using multiple assays, the transcriptional regulation of interferon-inducible transmembrane protein 1 (IFITM1) by PITX2 was studied at both molecular and functional levels. Results: PITX2 expression was induced in letrozole-resistant BCa tissues and cells, and PITX2 induction by IFNα signaling powerfully protected BCa cells against letrozole insult and potentiated letrozole-resistance. Mechanistically, PITX2 enhanced IFNα-induced AKT activation by transactivating the transcription of IFITM1, thus rendering BCa cells unresponsive to letrozole-elicited cell death. Additionally, ablation of IFITM1 expression using siRNA substantially abolished IFNα-elicited AKT phosphorylation, even in the presence of PITX2 overexpression, thus sensitizing BCa cells to letrozole treatment. Conclusion: These results demonstrate that constitutive upregulation of PITX2/IFITM1 cascade is an intrinsic adaptive mechanism during the pathogenesis of letrozole-resistance, and modulation of PITX2/IFITM1 level using different genetic and pharmacological means would thus have a novel therapeutic potential against letrozole resistance in BCa.

20.
Sci Rep ; 8(1): 8750, 2018 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-29884798

RESUMO

Long noncoding RNAs (lncRNAs) have an important role in adipose tissue function and energy metabolism homeostasis, and abnormalities may lead to obesity. To investigate whether lncRNAs are involved in childhood obesity, we investigated the differential expression profile of lncRNAs in obese children compared with non-obese children. A total number of 1268 differentially expressed lncRNAs and 1085 differentially expressed mRNAs were identified. Gene Ontology (GO) and pathway analysis revealed that these lncRNAs were involved in varied biological processes, including the inflammatory response, lipid metabolic process, osteoclast differentiation and fatty acid metabolism. In addition, the lncRNA-mRNA co-expression network and the protein-protein interaction (PPI) network were constructed to identify hub regulatory lncRNAs and genes based on the microarray expression profiles. This study for the first time identifies an expression profile of differentially expressed lncRNAs in obese children and indicated hub lncRNA RP11-20G13.3 attenuated adipogenesis of preadipocytes, which is conducive to the search for new diagnostic and therapeutic strategies of childhood obesity.

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