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1.
Dalton Trans ; 2019 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-31720636

RESUMO

A g-C3N4/ZnO/cellulose ternary composite (labeled as CNZCel) with an ordered structure and excellent antibacterial properties has been successfully synthesized via a facile method. Its morphology, microstructure and components have been analyzed by using XRD, SEM, TEM and EDS, and the results corroborate the co-existence of three components in the ternary composite. It is revealed that ZnO particles are connected to the layered g-C3N4 and simultaneously attached to the cellulose substrate. This microstructural feature is also borne out by the relativistic density functional study of a finite g-C3N4-ZnO-cellulose cluster. Both experimental and theoretical results unravel that the interfacial bonding interactions in the ternary composite improve electron transfer among components and enable high-efficiency spatial separation of photogenerated electrons and holes. Consequently, good antibacterial performance of the composite has been found in tests. This study provides the prospect of preparing low-cost and environment-friendly food packaging materials, which are also endowed with excellent antibacterial activity.

2.
Mol Med Rep ; 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31746387

RESUMO

The present study examined whether lipoxin A4 (LXA4) increases the expression of HO­1, and inhibits the production of interleukin 6 (IL­6) and monocyte chemotactic protein 1 (MCP­1) in LXA4­induced protection during hyperoxia­induced injury in murine lung epithelial cells (MLE­12) and what signal pathway may participate in the actions of LXA4 inhibiting IL­6 and MCP­1. MLE­12 cells were exposed to air or hyperoxia with or without pretreatment with LXA4, Zinc protoporphyrin IX (ZnPP­IX), IL­6, anti­IL­6, MCP­1, anti­MCP­1, inhibitors of p38 mitogen­activated protein kinase (p38 MAPK), protein kinase B (Akt) and extracellular signal­regulated kinase 1/2 (ERK1/2) signaling pathways. The cell survival rates, cell viability, apoptosis rates, expression of superoxide dismutase (SOD), heme oxygenase­1 (HO­1), IL­6 and MCP­1, and the activations of p38 MAPK, ERK1/2 and Akt were measured. LXA4 significantly increased the cell survival rates, cell viability, SOD levels and HO­1 expression, reduced the apoptosis rates, and inhibited the MCP­1 and IL­6 levels induced by hyperoxia in cells. ZnPP­IX, an inhibitor of HO­1, blocked LXA4­induced protection on cell viability in cells exposed to hyperoxia. Anti­IL­6 and anti­MCP­1 improved the cell viability of cells exposed to hyperoxia. Inhibition of p38 MAPK and ERK1/2 blocked the expression of MCP­1 and IL­6 induced by hyperoxia. LXA4 inhibited the activation of p38 MAPK and ERK1/2 induced by hyperoxia, and increased the activation of the Akt signaling pathway, which was inhibited by hyperoxia. Therefore, LXA4 attenuated hyperoxia­induced injury in MLE­12 cells via the upregulation of HO­1 expression. The protection of LXA4 in hyperoxia­induced cell injury may be associated with the downregulation IL­6 and MCP­1 levels via the inhibition of the p38 MAPK and ERK1/2 signaling pathways.

3.
Mol Ther ; 27(6): 1153-1165, 2019 06 05.
Artigo em Inglês | MEDLINE | ID: mdl-31010740

RESUMO

E2F transcription factors (E2Fs), a group of genes that encode a family of transcription factors, have been identified as being involved in the tumor progression of various cancer types. Increasing experimental evidence indicates that E2Fs are implicated in breast cancer tumorigenesis. However, the diverse expression patterns and prognostic values of eight E2Fs have yet to be analyzed. Herein we investigated the transcriptional and survival data of E2Fs in patients with breast cancer from the Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), Kaplan-Meier Plotter, and cBioPortal databases. We found that the expression levels of E2F1-3 and 5-8 were higher in breast cancer tissues than in normal breast tissues, whereas the expression level of E2F4 was lower in the former than in the latter. The expression levels of E2F2, 5, 7, and 8 were correlated with advanced tumor stage. Survival analysis using the Kaplan-Meier Plotter database revealed that the high transcription levels of E2F1-3, 5, 7, and 8 were associated with low relapse-free survival in all of the patients with breast cancer. Conversely, high E2F4 and E2F6 levels predicted high relapse-free survival in these patients. This study implied that E2F1-3, 5, 7, and 8 are potential targets of precision therapy for patients with breast cancer and that E2F4 and 6 are new biomarkers for the prognosis of breast cancer.

4.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(3): 287-293, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30907356

RESUMO

OBJECTIVE: To study the role of miR-431 in lung development and morphology. METHODS: According to the stage of lung development in rats, Sprague-Dawley rats at embryonic day 16 (E16), embryonic day (E19), embryonic day (E21), postnatal day 1 (P1), postnatal day 3 (P3), postnatal day 7 (P7), postnatal day 14 (P14) and 10 weeks after birth (P10 weeks) were selected, and lung tissue samples were collected for observation. Hematoxylin-eosin staining and transmission electron microscopy were performed to observe the morphology of lung tissue. Fluorescence in situ hybridization and real-time PCR were used to measure the expression of miR-431 during the critical stages of lung development (E19, E21 and P3). RESULTS: The E19 group had the formation of the lamellar body and type II alveolar epithelial cells in the fetal lung tissue. The number of lamellar bodies increased with the increasing gestational age, with aggregation and excretion. Pulmonary alveoli formed rapidly, the lung interstitium became thinner, and the microvascular system became mature after birth. Fluorescence in situ hybridization and real-time PCR showed that the expression of miR-431 gradually decreased with the increasing gestational age (P<0.05). CONCLUSIONS: The systematic and continuous morphological data of lung development is obtained in this experiment. In addition, miR-431 may play an important role in the negative regulation of lung development, which provides basis and direction for further research on the mechanism of lung development and related diseases.


Assuntos
Pulmão , Animais , Feto , Hibridização in Situ Fluorescente , MicroRNAs , Ratos , Ratos Sprague-Dawley
5.
Int J Mol Med ; 43(2): 980-992, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30535467

RESUMO

Our previous studies identified that the expression of microRNA­29c (miR­29c­3p) was significantly increased in the serum of pregnant women carrying fetuses with congenital heart disease (CHD) compared with in that of normal pregnant women. However, the mechanism by which miR­29c­3p affects development of the embryonic heart remained unclear. The aim of the present study was to investigate the effect and potential molecular mechanism of miR­29c­3p overexpression on P19 cell proliferation, apoptosis and differentiation. miR­29c­3p­overexpression and protein kinase Bγ (Akt3)­knockdown cell lines were constructed using transfection technology. The function of miR­29c­3p and Akt3 in cardiomyocyte development was investigated by determining the proliferation, apoptosis and differentiation of P19 cells, which can differentiate into cardiomyocytes induced by dimethylsulfoxide. Bioinformatic analysis and luciferase assays were performed to explore the association between Akt3 and miR­29c­3p. The results of the present study revealed that miR­29c­3p overexpression and Akt3 knockdown suppressed proliferation, and promoted apoptosis and differentiation in P19 cells. Akt3 was also demonstrated to be a target of miR­29c­3p. Therefore, overexpression of miR­29c­3p may inhibit proliferation, and promote apoptosis and differentiation in P19 cells by inhibiting the expression of Akt3. miR­29c­3p may be a potential therapeutic target for the treatment of CHD.


Assuntos
Regulação da Expressão Gênica , Cardiopatias Congênitas/etiologia , MicroRNAs/genética , Proteínas Proto-Oncogênicas c-akt/genética , Interferência de RNA , Animais , Biomarcadores , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Cardiopatias Congênitas/metabolismo , Cardiopatias Congênitas/patologia , Camundongos , Miócitos Cardíacos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Transfecção , Proteína X Associada a bcl-2/metabolismo
7.
Aging (Albany NY) ; 10(5): 973-987, 2018 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-29754146

RESUMO

E2F is a group of genes that encode a family of transcription factors (TFs) in higher eukaryotes and participate in cell cycle regulation and DNA synthesis in mammalian cells. Evidence from cell lines, mouse models, and human tissues indicates that TFs are implicated in lung cancer (LC) tumorigenesis. However, the diverse expression patterns and prognostic values of eight E2Fs have yet to be elucidated. In the current study, we examined the transcriptional and survival data of E2Fs in patients with LC from ONCOMINE, GEPIA, Kaplan-Meier Plotter, and cBioPortal databases. We found that the expression levels of E2F1/2/3/5/6/7/8 were higher in lung adenocarcinoma and squamous cell lung carcinoma tissues than in lung tissues, whereas the expression level of E2F4 was lower in the former than in the latter. The expression levels of E2F2/4/5/7/8 were correlated with advanced tumor stage. Survival analysis using the Kaplan-Meier Plotter database revealed that the high transcription levels of E2F1/2/4/5/7/8 were associated with low relapse-free survival (RFS) in all of the patients with LC. Conversely, high E2F3/6 levels predicted high RFS in these patients. This study implied that E2F3/6/7 are potential targets of precision therapy for patients with LC and that E2F1/2/4/5/8 are new biomarkers for the prognosis of LC.

8.
Sci Rep ; 8(1): 6623, 2018 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-29700340

RESUMO

Ti-24Nb-4Zr-8Sn (Ti2448), a new ß-type Ti alloy, consists of nontoxic elements and exhibits a low uniaxial tensile elastic modulus of approximately 45 GPa for biomedical implant applications. Nevertheless, the bio-corrosion resistance and biocompatibility of Ti2448 alloys must be improved for long-term clinical use. In this study, a rapid electrochemical anodization treatment was used on Ti2448 alloys to enhance the bio-corrosion resistance and bone cell responses by altering the surface characteristics. The proposed anodization process produces a unique hybrid oxide layer (thickness 50-120 nm) comprising a mesoporous outer section and a dense inner section. Experiment results show that the dense inner section enhances the bio-corrosion resistance. Moreover, the mesoporous surface topography, which is on a similar scale as various biological species, improves the wettability, protein adsorption, focal adhesion complex formation and bone cell differentiation. Outside-in signals can be triggered through the interaction of integrins with the mesoporous topography to form the focal adhesion complex and to further induce osteogenic differentiation pathway. These results demonstrate that the proposed electrochemical anodization process for Ti2448 alloys with a low uniaxial tensile elastic modulus has the potential for biomedical implant applications.

9.
J Paediatr Child Health ; 54(3): 284-288, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28960558

RESUMO

AIM: To determine the level of cystatin C (Cys-C) values in preterm babies for the purpose of becoming a good endogenous marker of renal function. METHODS: A total of 366 very low-birthweight infants (including 70 extremely low-birthweight babies) with gestational age <37 weeks born in two centres were studied. RESULTS: In very low-birthweight infants, the mean level of Cys-C was 1.96 ± 0.44 mg/L in blood samples taken on day 1, 1.78 ± 0.49 mg/L on day 7 and 1.71 ± 0.47 mg/L on day 28. In extremely low-birthweight infants, the mean level of Cys-C was 2.00 ± 0.49 mg/L on day 1, 1.63 ± 0.38 mg/L on day 7 and 1.62 ± 0.55 mg/L on day 28, respectively. Compared to serum creatinine and blood urea nitrogen, Cys-C level was independent of birthweight and gestational age. CONCLUSION: Cys-C is regarded as an alternative for assessing renal function in very low-birthweight infants, but its advantages over serum creatinine and blood urea nitrogen has not been fully proved yet. Hence, larger sample study is still necessary.

10.
Mol Ther Nucleic Acids ; 9: 100-110, 2017 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-29246288

RESUMO

Long noncoding RNAs (lncRNAs) are emerging as important regulators during tumorigenesis by serving as competing endogenous RNAs (ceRNAs). In this study, the qRT-PCR results indicated that the lncRNA protein disulfide isomerase family A member 3 pseudogene 1 (PDIA3P) was overexpressed in oral squamous cell carcinoma (OSCC) and decreased the survival rate of OSCC patients. CCK-8 and clonal colony formation assays were used to detect the effects of PDIA3P on proliferation. Results revealed that silencing PDIA3P by small interfering RNA (siRNA) inhibited OSCC cell proliferation and repressed tumor growth and reduced the expression of proliferation antigen Ki-67 in vivo. Furthermore, the interaction between PDIA3P and miRNAs was then analyzed by qRT-PCR and luciferase reporter gene assay. We found that PDIA3P negatively regulated miR-185-5p in OSCC cells. Simultaneously, we found that silencing PDIA3P by siRNA suppressed proliferation via miR-185-5p in OSCC cells. Moreover, silencing PDIA3P by siRNA inhibited CCND2 protein (no influence on mRNA levels) expression via miR-185-5p in OSCC cells, and CCND2 facilitated cell proliferation of SCC4 and SCC15 cells induced by sh-PDIA3P#1. Therefore, our study demonstrated that PDIA3P may be a therapeutic target for the treatment of OSCC.

11.
Cell Prolif ; 50(6)2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28990243

RESUMO

BACKGROUND: Lung cancer is still one of the most serious causes of cancer-related deaths all over the world. MicroRNAs (miRNAs) are defined as small non-coding RNAs which could play a pivotal role in post-transcriptional regulation of gene expression. Increasing evidence demonstrated dysregulation of miRNA expression associates with the development and progression of NSCLC. AIMS: To emphasize a variety of tissue-specific miRNAs, circulating miRNAs and miRNA-derived exosomes could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. MATERIALS & METHODS: In the current review, we paid attention to the significant discoveries of preclinical and clinical studies, which performed on tissue-specific miRNA, circulating miRNA and exosomal miRNA. The related studies were obtained through a systematic search of Pubmed, Web of Science, Embase. RESULTS: A variety of tissue-specific miRNAs and circulating miRNAs with high sensitivity and specificity which could be used as potential diagnostic and therapeutic biomarkers in NSCLC patients. In addition, we emphasize that the miRNA-derived exosomes become novel diagnostic biomarkers potentially in these patients with NSCLC. CONCLUSION: MiRNAs have emerged as non-coding RNAs, which have potential to be candidates for the diagnosis and therapy of NSCLC.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Pulmonar de Células não Pequenas/diagnóstico , Carcinoma Pulmonar de Células não Pequenas/terapia , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/terapia , MicroRNAs/genética , Animais , Carcinoma Pulmonar de Células não Pequenas/genética , Exossomos/genética , Exossomos/metabolismo , Perfilação da Expressão Gênica/métodos , Humanos , Neoplasias Pulmonares/genética
12.
Mol Ther Nucleic Acids ; 8: 442-449, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28918043

RESUMO

Lung cancer is a deadly disease that ends numerous lives around the world. MicroRNAs (miRNAs) are a group of non-coding RNAs involved in a variety of biological processes, such as cell growth, organ development, and tumorigenesis. The miR-206/133b cluster is located on the human chromosome 6p12.2, which is essential for growth and rebuilding of skeletal muscle. The miR-206/133b cluster has been verified to be dysregulated and plays a crucial role in lung cancer. miR-206 and miR-133b participate in lung tumor cell apoptosis, proliferation, migration, invasion, angiogenesis, drug resistance, and cancer treatment. The mechanisms are sophisticated, involving various target genes and molecular pathways, such as MET, EGFR, and the STAT3/HIF-1α/VEGF signal pathway. Hence, in this review, we summarize the role and potential mechanisms of the miR-206/133b cluster in lung cancer.

13.
Inflammation ; 40(6): 2094-2108, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28819748

RESUMO

Transforming growth factor-ß (TGF-ß) superfamily members are key regulators for lung development and progress of bronchopulmonary dysplasia (BPD). The mechanisms by which lipoxin A4 (LXA4) attenuates development of BPD have not been clarified. Neonatal murine BPD models were inducted by hyperoxia treatment. Neonatal mice were exposed to room air or 85% O2 hyperoxia with or without treatment with 5S,6R-methyl-LXA4 or anti-TGF-ß antibodies. Mouse lung epithelial cells (MLE-12 cells) and mouse embryonic fibroblasts (NIH/3T3 cells) were cultured in room air or 85% O2 followed by treatment of LXA4, anti-TGF-ß antibodies, and let-7c mimic/anti-microRNA transfections. Treatment with 5S,6R-methyl-LXA4 and anti-TGF-ß antibodies both attenuated the mice alveolar simplification induced by hyperoxia. Hyperoxia treatment significantly altered pulmonary basal mRNA and protein expressions of several important extracellular matrix (ECM) and ECM remodeling proteins including fibronectin, α-smooth muscle actin (α-SMA), tissue inhibitor of metalloproteinase-1 (TIMP-1), elastin, tenascin C, collagen I, and matrix metalloproteinase-1 (MMP-1). 5S,6R-methyl-LXA4 and anti-TGF-ß antibodies suppressed the mRNA and protein expressions of TGF-ß1 and TGF-ßR1 but not TGF-ßR2 in the lungs exposed to hyperoxia. Treatment with LXA4 and anti-TGF-ß antibodies alleviated hyperoxia-induced injury of the NIH/3T3 cells identified by morphologic observation and flow cytometry, and expressions of ECM, ECM remodeling proteins, and TGF-ß1 signaling pathway, but reversed by transfection with let-7c anti-miRNA. LXA4 upregulated the let-7c expression in MLE-12 cells, transfection with let-7c anti-miRNA, inhibited the LXA4-induced let-7c expression in MLE-12 cells exposed to hyperoxia and reduced the relative luciferase activity of let-7c binding with let-7c binding sites of the TGF-ßR1 3' UTR. Treatment with 5S,6R-methyl-LXA4 and anti-TGF-ß antibodies significantly improved histology, ECM, and ECM remodeling proteins in the lungs isolated from the murine BPD model induced by hyperoxia. The LXA4-imparted protective effects on hyperoxia-induced lung injury are mediated by upregulation of let-7c and inhibition of TGF-ß1 and subsequent downregulation of TGF-ß1 signaling pathway.


Assuntos
Displasia Broncopulmonar/prevenção & controle , Lipoxinas/farmacologia , MicroRNAs/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta1/metabolismo , Animais , Animais Recém-Nascidos , Anti-Inflamatórios não Esteroides/farmacologia , Displasia Broncopulmonar/tratamento farmacológico , Regulação para Baixo/efeitos dos fármacos , Camundongos , Células NIH 3T3 , Regulação para Cima
14.
Mol Ther Nucleic Acids ; 6: 140-149, 2017 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-28325280

RESUMO

MicroRNAs (miRNAs) are small noncoding RNAs approximately 20-25 nt in length, which play crucial roles through directly binding to corresponding 3' UTR of targeted mRNAs. It has been reported that miRNAs are involved in numerous of diseases, including cancers. Recently, miR-134 has been identified to dysregulate in handles of human cancers, such as lung cancer, glioma, breast cancer, colorectal cancer, and so on. Increasing evidence indicates that miR-134 is essential for human carcinoma and participates in tumor cell proliferation, apoptosis, invasion and metastasis, drug resistance, as well as cancer diagnosis, treatment, and prognosis. Nevertheless, its roles in human cancer are still ambiguous, and its mechanisms are sophisticated as well, referring to a variety of targets and signal pathways, such as STAT5B, KRAS, MAPK/ERK signal pathway, Notch pathway, etc. Herein, we review the crucial roles of miR-134 in scores of human cancers via analyzing latest investigations, which might provide evidence for cancer diagnose, treatment, prognosis, or further investigations.

15.
Mol Med Rep ; 15(3): 1313-1318, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28112377

RESUMO

Hemophilia B occurs due to a deficiency in human blood coagulation factor IX (hFIX). Currently, no effective treatment for hemophilia B has been identified, and gene therapy has been considered the most appropriate treatment. Mesenchymal stem cells (MSCs) have homing abilities and low immunogenicity, and therefore they may be potential cell carriers for targeted drug delivery to lesional tissues. The present study constructed an adeno­associated virus integration site 1 (AAVS1)­targeted vector termed AAVS1­green fluorescent protein (GFP)­hFIX and a zinc finger nuclease (ZFN) expression vector. Nucleofection was used to co­transfect the targeting vector and the ZFN expression vector into human MSCs. The GFP­positive cells were selected using flow cytometry. Site­specific integration clones were obtained following the monoclonal culture, subsequent detections were performed using polymerase chain reaction and Southern blotting. Following the confirmation of stem cell traits of the site­specific integration MSCs, the in vivo and in vitro expression levels of hFIX were detected. The results demonstrated that the hFIX gene was successfully transfected into the AAVS1 locus in human MSCs. The clones with the site­specific integration retained stem cell traits of the MSCs. In addition, hFIX was effectively expressed in vivo and in vitro. No significant differences in expression levels were identified among the individual clones. In conclusion, the present study demonstrated that the exogenous gene hFIX was effectively expressed following site­specific targeting into the AAVS1 locus in MSCs; therefore, MSCs may be used as potential cell carriers for gene therapy of hemophilia B.


Assuntos
Dependovirus/genética , Fator IX/genética , Expressão Gênica , Marcação de Genes , Loci Gênicos , Vetores Genéticos/genética , Células-Tronco Mesenquimais/metabolismo , Integração Viral , Adulto , Animais , Diferenciação Celular , Ordem dos Genes , Genes Reporter , Humanos , Masculino , Células-Tronco Mesenquimais/citologia , Adulto Jovem
16.
Mol Ther Nucleic Acids ; 5(11): e387, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27845771

RESUMO

MicroRNAs have been identified to be involved in center stage of cancer biology. They accommodate cell proliferation and migration by negatively regulate gene expression either by hampering the translation of targeted mRNAs or by promoting their degradation. We characterized and identified the novel miR-9600 and its target in human non-small-cell lung cancer (NSCLC). Our results demonstrated that the miR-9600 were downregulated in NSCLC tissues and cells. It is confirmed that signal transducer and activator of transcription 3 (STAT3), a putative target gene, is directly inhibited by miR-9600. The miR-9600 markedly suppressed the protein expression of STAT3, but with no significant influence in corresponding mRNA levels, and the direct combination of miR-9600 and STAT3 was confirmed by a luciferase reporter assay. miR-9600 inhibited cell growth, hampered expression of cell cycle-related proteins and inhibited cell migration and invasion in human NSCLC cell lines. Further, miR-9600 significantly suppressed tumor growth in nude mice. Similarly, miR-9600 impeded tumorigenesis and metastasis through directly targeting STAT3. Furthermore, we identified that miR-9600 augmented paclitaxel and cisplatin sensitivity by downregulating STAT3 and promoting chemotherapy-induced apoptosis. These data demonstrate that miR-9600 might be a useful and novel therapeutic target for NSCLC.

17.
Mol Ther Nucleic Acids ; 5(11): e385, 2016 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-27845772

RESUMO

Long noncoding RNAs (lncRNAs) play crucial roles in carcinogenesis. However, the function and mechanism of lncRNAs in human non-small-cell lung cancer (NSCLC) are still remaining largely unknown. Long intergenic noncoding RNA 00511 (LINC00511) has been found to be upregulated and acts as an oncogene in breast cancer, but little is known about its expression pattern, biological function and underlying mechanism in NSCLC. Herein, we identified LINC00511 as an oncogenic lncRNA by driving tumorigenesis in NSCLC. We found LINC00511 was upregulated and associated with oncogenesis, tumor size, metastasis, and poor prognosis in NSCLC. Moreover, LINC00511 affected cell proliferation, invasiveness, metastasis, and apoptosis in multiple NSCLC cell lines. Mechanistically, LINC00511 bound histone methyltransferase enhancer of zeste homolog 2 ((EZH2, the catalytic subunit of the polycomb repressive complex 2 (PRC2), a highly conserved protein complex that regulates gene expression by methylating lysine 27 on histone H3), and acted as a modular scaffold of EZH2/PRC2 complexes, coordinated their localization, and specified the histone modification pattern on the target genes, including p57, and consequently altered NSCLC cell biology. Thus, LINC00511 is mechanistically, functionally, and clinically oncogenic in NSCLC. Targeting LINC00511 and its pathway may be meaningful for treating patients with NSCLC.

18.
Nan Fang Yi Ke Da Xue Xue Bao ; 36(9): 1215-1220, 2016 08 20.
Artigo em Chinês | MEDLINE | ID: mdl-27687653

RESUMO

OBJECTIVE: To investigate the correlation of CD4+CD29+ regulatory T cells (Treg) with tumor recurrence and survival time in patients with non-small cell lung cancer (NSCLC). METHODS: Fifty-nine patients with NSCLC treated with radical surgery were followed up for 5 years. Blood Treg cells were examined during the follow-up using flow cytometry (FCM). The sensitivity and specificity of Treg cells to predict recurrence of NSCLC were analyzed using receiver-operating characteristic (ROC) curve and compared with those of carcinoembryonic antigen (CEA) and cytokeratin21-1 (Cyfra21-1). The influences of gender, age, occupation and radiotherapy on survival time of the patients were analyzed with Kaplan-Meier method. RESULTS: Among the 59 patients, the shortest survival time was 23 months while the longest time was over 67 months. Nineteen patients had NSCLC recurrence, and 17 (28.81%) of them died of metastasis during the follow-up. The frequencies of blood Treg cells in patients who did not receive radiotherapy and in patients with tumor recurrence were significantly higher than those in patients receiving radiotherapy and in patients free of recurrence (P=0.000). ROC curves showed that the area under curve (AUC) lowered in the order of Treg cells, Cyfra21-1, CEA (P=0.002, 0.006 and 0.013, respectively) with 95% confidence interval (CI) of 0.649-0.981, 0.621-0.936 and 0.584-0.944, respectively. At the cut-off value of 7.53%, the sensitivity and specificity of Treg cells to predict NSCLC recurrence was 91.42% and 87.59%, respectively. The five-year survival rate of the 59 patients was 71.18% (42/59), and Kaplan-Meier analysis revealed a longer survival time in female patients (P=0.038), in patients below 50 years of age (P=0.013), in patients not engaging in mental work (P=0.029), and in patients receiving radiotherapy (P=0.003). CONCLUSION: Treg cells has a better efficiency than Cyfra21-1 and CEA to predict tumor recurrence in patients with NSCLC following radical surgery. The male gender, an age beyond 50 years, an occupation of mental work, and failure to receive radiotherapy are all risk factors for recurrence of NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Linfócitos T Reguladores/citologia , Antígenos de Neoplasias/metabolismo , Biomarcadores Tumorais/metabolismo , Antígeno Carcinoembrionário/metabolismo , Feminino , Humanos , Queratina-19/metabolismo , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Prognóstico , Curva ROC , Fatores de Risco , Sensibilidade e Especificidade
19.
Aging (Albany NY) ; 8(10): 2509-2524, 2016 10 18.
Artigo em Inglês | MEDLINE | ID: mdl-27777383

RESUMO

Determinants of growth and metastasis in cancer remain of great interest to define. MicroRNAs (miRNAs) have frequently emerged as tumor metastatic regulator by acting on multiple signaling pathways. Here we report the definition of miR-346 as a novel oncogenic microRNA that facilitates non-small cell lung cancer (NSCLC) cell growth and metastasis. XPC, an important DNA damage recognition factor in nucleotide excision repair was defined as a target for down-regulation by miR-346, functioning through direct interaction with the 3'-UTR of XPC mRNA. Blocking miR-346 by an antagomiR was sufficient to inhibit NSCLC cell growth and metastasis, an effect that could be phenol-copied by RNAi-mediated silencing of XPC. In vivo studies established that miR-346 overexpression was sufficient to promote tumor growth by A549 cells in xenografts mice, relative to control cells. Overall, our results defined miR-346 as an oncogenic miRNA in NSCLC, the levels of which contributed to tumor growth and invasive aggressiveness.


Assuntos
Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proliferação de Células/fisiologia , Neoplasias Pulmonares/metabolismo , MicroRNAs/metabolismo , Metástase Neoplásica/genética , Transdução de Sinais/fisiologia , Regiões 3' não Traduzidas , Animais , Caderinas/genética , Caderinas/metabolismo , Carcinogênese/genética , Carcinogênese/patologia , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Dano ao DNA , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , MAP Quinases Reguladas por Sinal Extracelular/genética , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , MicroRNAs/genética , Metástase Neoplásica/patologia , Interferência de RNA , Fatores de Transcrição da Família Snail/genética , Fatores de Transcrição da Família Snail/metabolismo
20.
Oncotarget ; 7(24): 35960-35978, 2016 Jun 14.
Artigo em Inglês | MEDLINE | ID: mdl-27166267

RESUMO

Hsa-miRNA-134 (miR-134) has recently been discovered to have anticancer efficacy in different organs. However, the role of miR-134 on non-small cell lung cancer (NSCLC) is still ambiguous. In this study, we investigated the role of miR-134 on the development of NSCLC. The results indicated that miR-134 was significantly down-regulated in primary tumor tissues and very low levels were found in NSCLC cell lines. Ectopic expression of miR-134 in NSCLC cell lines significantly suppressed cell growth as evidenced by cell viability assay, colony formation assay and BrdU staining, through inhibition of cyclin D1, cyclin D2, CDK4 and up-regulation of p57(Kip2) and p21(Waf1/Cip1). In addition, miR-134 induced apoptosis, as indicated by concomitantly with up-regulation of key apoptosis protein cleaved caspase-3, and down-regulation of anti-apoptosis protein Bcl2. Moreover, miR-134 inhibited cellular migration and invasiveness through inhibition of matrix metalloproteinases (MMP)-7 and MMP-9. Further, oncogene CCND1 was revealed to be a putative target of miR-134, which was inversely correlated with miR-134 expression in NSCLC. Taken together, our results demonstrated that miR-134 played a pivotal role on NSCLC through inhibiting cell proliferation, migration, invasion, and promoting apoptosis by targeting oncogenic CCND1.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Ciclina D1/genética , Regulação para Baixo , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , MicroRNAs/genética , Células A549 , Idoso , Animais , Apoptose/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Ciclina D1/metabolismo , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Pessoa de Meia-Idade , Transplante Heterólogo
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