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1.
Molecules ; 26(4)2021 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-33672678

RESUMO

Idiopathic pulmonary fibrosis (IPF) is a lethal, agnogenic interstitial lung disease with limited therapeutic options. To investigate vital genes involved in the development of IPF, we integrated and compared four expression profiles (GSE110147, GSE53845, GSE24206, and GSE10667), including 87 IPF samples and 40 normal samples. By reanalyzing these datasets, we managed to identify 62 upregulated genes and 20 downregulated genes in IPF samples compared with normal samples. Differentially expressed genes (DEGs) were analyzed by gene ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis to illustrate relevant pathways of IPF, biological processes, molecular function, and cell components. The DEGs were then subjected to protein-protein interaction (PPI) for network analysis, serving to find 11 key candidate genes (ANXA3, STX11, THBS2, MMP1, MMP9, MMP7, MMP10, SPP1, COL1A1, ITGB8, IGF1). The result of RT-qPCR and immunohistochemical staining verified our finding as well. In summary, we identified 11 key candidate genes related to the process of IPF, which may contribute to novel treatments of IPF.


Assuntos
Fibrose Pulmonar Idiopática/genética , Anexina A3/genética , Colágeno Tipo I/genética , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Ontologia Genética , Humanos , Fator de Crescimento Insulin-Like I/genética , Cadeias beta de Integrinas/genética , Metaloproteinases da Matriz/genética , Osteopontina/genética , Mapas de Interação de Proteínas , Proteínas Qa-SNARE/genética , Trombospondinas/genética
2.
Am J Pathol ; 190(11): 2317-2326, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32861643

RESUMO

The adipocyte-like morphology of clear cell renal cell carcinoma (ccRCC) cells results from a grade-dependent neutral lipid accumulation; however, the molecular mechanism and role in renal cancer progression have yet to be clarified. ccRCC shows a gene expression signature consistent with adipogenesis, and the phospholipid-binding protein annexin A3 (AnxA3), a negative regulator of adipocyte differentiation, is down-regulated in RCC and shows a differential expression pattern for two isoforms of 36 and 33 kDa. Using primary cell cultures and cell lines, we investigated the involvement of AnxA3 isoforms in lipid storage modulation of ccRCC cells. We found that the increased accumulation of lipids into ccRCC cells correlated with a decrease of the 36/33 isoform ratio. Treatment with adipogenic medium induced a significant increment of lipid storage in ccRCC cells that had a low 36-kDa AnxA3 expression and 36/33 ratio. The 36-kDa AnxA3 silencing in ccRCC cells increased lipid storage induced by adipogenic medium. These data suggest that 36-kDa AnxA3 negatively modulates the response to adipogenic treatment and may act as negative regulator of lipid storage in ccRCC cells. The subcellular distribution of AnxA3 in the cellular endocytic compartment suggests its involvement in modulation of vesicular trafficking, and it might serve as a putative mechanism of lipid storage regulation in ccRCC cells, opening novel translational outcomes.


Assuntos
Anexina A3/metabolismo , Carcinoma de Células Renais/metabolismo , Neoplasias Renais/metabolismo , Metabolismo dos Lipídeos , Proteínas de Neoplasias/metabolismo , Idoso , Carcinoma de Células Renais/patologia , Linhagem Celular Tumoral , Feminino , Humanos , Isoenzimas/metabolismo , Neoplasias Renais/patologia , Masculino
3.
PLoS One ; 15(1): e0227606, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31935243

RESUMO

Cardiovascular disease (CVD) risks persist in patients despite treatment. CVD susceptibility also varies with sex and ethnicity and is not entirely explained by conventional CVD risk factors. The aim of the present study was to identify novel CVD candidate markers in circulating Peripheral blood mononuclear cells (PBMCs) and plasma from Arab obese subjects with and without CVD using proteomic approaches. Human adults with confirmed CVD (n = 208) and matched non-CVD controls (n = 152) living in Kuwait were examined in the present cross-sectional study. Anthropometric and classical biochemical parameters were determined. We employed a shotgun proteomic profiling approach on PBMCs isolated from a subset of the groups (n = 4, each), and differentially expressed proteins selected between the two groups were validated at the mRNA level using RT-PCR (n = 6, each). Plasma levels of selected proteins from the proteomics profiling: Proteinase-3 (PR3), Annexin-A3 (ANX3), Defensin (DEFA1), and Matrix Metalloproteinase-9 (MMP9), were measured in the entire cohort using human enzyme-linked immunosorbent assay kits and were subsequently correlated with various clinical parameters. Out of the 1407 we identified and quantified from the proteomics profiling, 47 proteins were dysregulated with at least twofold change between the two subject groups. Among the differentially expressed proteins, 11 were confirmed at the mRNA levels. CVD influenced the levels of the shortlisted proteins (MMP9, PR3, ANX3, and DEFA1) in the PBMCs and plasma differentially. Despite the decreased levels of both protein and mRNA in PBMCs, PR3 circulating levels increased significantly in patients with CVD and were influenced by neither diabetes nor statin treatment. No significant changes were; however, observed in the DEFA1, MMP9, and ANX3 levels in plasma. Multivariate logistic regression analysis revealed that only PR3 was independently associated with CVD. Our results suggest that the dysregulation of PR3 levels in plasma and PBMCs reflects underlying residual CVD risks even in the treated population. More prospective and larger studies are required to establish the role of PR3 in CVD progression.


Assuntos
Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/metabolismo , Mieloblastina/metabolismo , Adulto , Anexina A3/análise , Anexina A3/sangue , Anexina A3/metabolismo , Árabes , Estudos Transversais , Defensinas/análise , Defensinas/sangue , Defensinas/metabolismo , Feminino , Perfilação da Expressão Gênica , Humanos , Kuweit/epidemiologia , Leucócitos/metabolismo , Leucócitos Mononucleares/metabolismo , Masculino , Metaloproteinase 9 da Matriz/análise , Metaloproteinase 9 da Matriz/sangue , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Mieloblastina/análise , Mieloblastina/sangue , Plasma/metabolismo , Estudos Prospectivos , Proteômica , RNA Mensageiro/genética
4.
Eur Arch Psychiatry Clin Neurosci ; 270(4): 489-494, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31372726

RESUMO

The cellular and molecular mechanisms underlying onset and development of schizophrenia have not yet been completely elucidated, but the association of disturbed neuroplasticity and inflammation has gained particular relevance recently. These mechanisms are linked to annexins functions. ANXA3, particularly, is associated to inflammation and membrane metabolism cascades. The aim was to determine the ANXA3 levels in first-onset drug-naïve psychotic patients. We investigated by western blot the protein expression of annexin A3 in platelets of first-onset, drug-naïve psychotic patients (diagnoses according to DSM-IV: 28 schizophrenia, 27 bipolar disorder) as compared to 30 age- and gender-matched healthy controls. Annexin A3 level was lower in schizophrenia patients as compared to healthy controls (p < 0.001) and to bipolar patients (p < 0.001). Twenty out of 28 schizophrenic patients had undetectable annexin A3 levels, as compared to none from the bipolar and none from the control subjects. ANXA3 was reduced in drug-naïve patients with schizophrenia. ANXA3 affects neuroplasticity, inflammation and apoptosis, as well as it modulates membrane phospholipid metabolism. All these processes have been discussed in regard to the biology of schizophrenia. In face of these data, we feel that further studies with larger samples are warranted to investigate the possible role of reduced ANXA3 as a possible risk marker for schizophrenia.


Assuntos
Anexina A3/sangue , Transtorno Bipolar/sangue , Esquizofrenia/sangue , Adulto , Biomarcadores/sangue , Feminino , Humanos , Masculino , Adulto Jovem
6.
Mediators Inflamm ; 2019: 4567106, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31772502

RESUMO

Aim: Aware that Down Syndrome patients present among their clinical characteristics impaired immunity, the aim of this study is to identify the statistically significant differences in inflammation-related gene expression by comparing Down Syndrome patients with Periodontal Disease (DS+PD+) with Down Syndrome patients without Periodontal Disease (DS+PD-), and their relationship with periodontitis as a chronic oral inflammatory clinical feature. Materials and Methods: Case study and controls on eleven Down Syndrome patients (DS+PD+ vs. DS+PD-). RNA was extracted from peripheral blood using a Qiagen PAXgene Blood miRNA Kit when performing an oral examination. A search for candidate genes (92 selected) was undertaken on the total genes obtained using a Scientific GeneChip® Scanner 3000 (Thermo Fisher Scientific) and Clariom S solutions for human, mouse, and rat chips, with more than 20,000 genes annotated for measuring expression levels. Results: Of the 92 inflammation-related genes taken initially, four genes showed a differential expression across both groups with a p value of <0.05 from the data obtained using RNA processing of the patient sample. Said genes were TNFSF13B (p = 0.0448), ITGB2 (p = 0.0033), ANXA3 (p = 0.0479), and ANXA5 (p = 0.016). Conclusions: There are differences in inflammation-related gene expression in Down Syndrome patients when comparing patients who present a state of chronic oral inflammation with patients with negative rates of periodontal disease.


Assuntos
Síndrome de Down/imunologia , Síndrome de Down/metabolismo , Inflamação/imunologia , Inflamação/metabolismo , Anexina A3/genética , Anexina A3/metabolismo , Fator Ativador de Células B/genética , Fator Ativador de Células B/metabolismo , Feminino , Humanos , Integrina beta3/genética , Integrina beta3/metabolismo , Masculino , Doenças Periodontais/imunologia , Doenças Periodontais/metabolismo , Periodontite/imunologia , Periodontite/metabolismo
7.
Mol Med Rep ; 20(3): 2583-2590, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31524248

RESUMO

Annexin A3 (ANXA3) is highly expressed in different types of cancers, but the impact of ANXA3 in bone tumors is still not clear. In the present study, the expression of ANXA3 in osteosarcoma cells was first confirmed by cellular immunofluorescence. Reverse transcription­quantitative polymerase chain reaction (RT­qPCR) and western blot analysis were used to detect the expression of ANXA3 in osteoblasts in the osteosarcoma cell lines U2OS and HOS. Furthermore, small interfering (si)­RNA were transfected into U2OS and HOS cells via a liposome­mediated method. Then once ANXA3 had been successfully downregulated in U2OS and HOS cells, the cells were collected and total protein was extracted after 48 h of transfection. Western blot analysis was used to confirm successful ANXA3 transfection into osteosarcoma cells and the apoptotic rate of HOS and U2OS was detected by flow cytometry. The expression of ANXA3 in the osteosarcoma cell lines HOS and U2OS were first observed by confocal laser scanning microscopy, and was then detected by RT­qPCR and western blotting. The mRNA and protein levels of ANXA3 in the osteosarcoma cell lines HOS and U2OS were significantly increased compared with osteoblasts, particularly in HOS cells. When siRNA was transfected into HOS and U2OS cells, the protein expression level of ANXA3 was measured via western blotting. The results indicated that the expression of ANXA3 was significantly decreased. In addition, to determine whether ANXA3 knockdown induced cell apoptosis, the present study analyzed the apoptotic rate by flow cytometry. The results revealed that ANXA3 knockdown markedly increased HOS and U2OS cell apoptosis. To the best of our knowledge, the present study is the first to confirm that ANXA3 is highly expressed in the osteosarcoma cell lines HOS and U2OS. In addition, downregulation of ANXA3 expression in HOS and U2OS cells could increase apoptotic ability.


Assuntos
Anexina A3/genética , Neoplasias Ósseas/genética , Expressão Gênica , Osteossarcoma/genética , Apoptose/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Humanos , Osteoblastos/metabolismo , Osteossarcoma/metabolismo , RNA Mensageiro/genética
8.
Toxicol Lett ; 313: 150-158, 2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31276768

RESUMO

Ochratoxin A (OTA), one of the most abundant food-contaminating mycotoxins, is a possible carcinogen to humans. We previously demonstrated that long-term (40 weeks) OTA exposure induces the malignant transformation of human gastric epithelium cells (GES-1) in vitro. However, the specific mechanism underlying OTA-induced gastric carcinogenesis is complex. In the present study, we used 2-DE and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI/TOF MS) combined with bioinformatics and immunoblotting to investigate the differentially expressed proteins between GES-1 and OTA-malignant transformed GES-1 cells (OTA-GES-1T cells) in vitro. We found that four differentially expressed proteins were identified after malignant transformation, including actin, cytoplasmic 1 (ACTB), F-actin-capping protein subunit alpha-1 (CAPZA1), Annexin A3 (ANXA3), thioredoxin peroxidase B from red blood cells (TPx-B) and Fibrinogen beta B (Fibrinogen ß). Among the differentially expressed proteins, the effect of Annexin A3 was analyzed by MTT assay, western blot, cell cycle analysis, wound healing assay, Transwell assay, and colony formation assay in OTA-GES-1T cells. The results showed that inhibition of Annexin A3 by siRNA effectively prevented the proliferation, migration, and invasion abilities of OTA-GES-1T cells. Collectively, the results of this study will guide future research on OTA carcinogenicity.


Assuntos
Anexina A3/metabolismo , Carcinógenos/toxicidade , Transformação Celular Neoplásica/induzido quimicamente , Células Epiteliais/efeitos dos fármacos , Mucosa Gástrica/efeitos dos fármacos , Ocratoxinas/toxicidade , Neoplasias Gástricas/induzido quimicamente , Anexina A3/genética , Western Blotting , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transformação Celular Neoplásica/genética , Transformação Celular Neoplásica/metabolismo , Transformação Celular Neoplásica/patologia , Biologia Computacional , Eletroforese em Gel Bidimensional , Células Epiteliais/metabolismo , Células Epiteliais/patologia , Mucosa Gástrica/metabolismo , Mucosa Gástrica/patologia , Humanos , Invasividade Neoplásica , Proteômica/métodos , Transdução de Sinais/efeitos dos fármacos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz , Neoplasias Gástricas/genética , Neoplasias Gástricas/metabolismo , Neoplasias Gástricas/patologia
9.
J BUON ; 24(2): 522-528, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31128000

RESUMO

PURPOSE: To observe the efficacy of neoadjuvant chemotherapy (NAC) in patients with breast cancer (BC) and to investigate the effect of Annexin A3 (ANXA3) expression. METHODS: 158 patients with BC treated in Yantai Yuhuangding Hospital from September 2015 to December 2017 were retrospectively analyzed. Among them, 83 cases were treated with epirubicin + cyclophosphamide + 5-fluorouracil (CEF group), 75 cases with epirubicin + cyclophosphamide + docetaxel (TEC group), with 3 cycles of chemotherapy. The efficacy and adverse reactions of the two NAC regimens were compared and analyzed. Tissue specimens were collected before and 10 days after the administration of chemotherapy in order to detect the expression of ANXA3 by qRT-PCR in each group. RESULTS: There were significant differences in the rates of complete remission (CR), partial remission (PR), stable disease (SD), and progressive disease (PD) between the two groups (z=10.716, p=0.013). The clinical effectiveness rate in the TEC group was significantly higher than that in the CEF group (p<0.05). There was no difference in the pathology grade between the two groups (p>0.05); however, the pathological effective rate in the TEC group was significantly higher than that in the CEF group (p<0.05). There was no difference in the rate of bone marrow suppression between the two groups (p>0.05). While there was no difference in the relative expression of ANXA3 between the two groups before chemotherapy, the relative expression of ANXA3 in the TEC group was lower than that in the CEF group after NAC (p<0.05). The relative expression in both groups after chemotherapy was lower than that before NAC (P<0.05). CONCLUSION: Compared with CEF regimen, NAC with TEC regimen can improve the clinical and pathological effectiveness rate, inhibit the expression of ANXA3, and improve the prognosis of patients, thus having a certain application prospect in NAC.


Assuntos
Anexina A3/genética , Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/efeitos adversos , Idoso , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Citarabina/administração & dosagem , Citarabina/efeitos adversos , Intervalo Livre de Doença , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Etoposídeo/administração & dosagem , Etoposídeo/efeitos adversos , Feminino , Fluoruracila/administração & dosagem , Fluoruracila/efeitos adversos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Pessoa de Meia-Idade , Prognóstico , Indução de Remissão , Taxoides/administração & dosagem , Taxoides/efeitos adversos
10.
J Cell Biochem ; 120(9): 14585-14593, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30998268

RESUMO

Colorectal cancer (CRC) is a common disease with high mortality and morbidity. Annexin A3 (ANXA3) belongs to the structurally homologous family of Ca2+ and phospholipid-binding proteins. This study aimed to investigate the effects and potential mechanisms of ANXA3 on oxaliplatin (Ox) resistance in CRC. We generated two human CRC cell lines (HCT116/Ox and SW480/Ox) with acquired Ox resistance and determined their resistance properties. ANXA3 expression and cell apoptosis, migration and invasion also were evaluated. We found that cell viability of HCT116/Ox and SW480/Ox was higher than that in parental cells in the presence of Ox. ANXA3 was highly expressed in HCT116/Ox and SW480/Ox cells. ANXA3 downregulation diminished cell survival, migration and invasion, while increased the apoptosis of HCT116 and SW480 with or without Ox. Moreover, depletion of ANXA3 reduced cell viability and BrdU incorporation, increased cell apoptosis and c-caspase 3 expression in HCT116/Ox with or without Ox. A transwell assay determined that knockdown of ANXA3 impeded the migration and invasion of HCT116/Ox and SW480/Ox cells. Additionally, phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) decreased upon ANXA3 depletion in HCT116/Ox cells, and ANXA3 silencing suppressed Ox-induced activation of ERK and JNK signaling pathway. ANXA3 downregulation reduced Ox resistance in CRC, and treatment with the ERK inhibitor PD098059 or JNK inhibitor SP600125 contributed to this process. These results indicate that silencing ANXA3 could overcome Ox resistance in CRC via the mitogen-activated protein kinase signaling pathway.


Assuntos
Anexina A3/genética , Neoplasias Colorretais/genética , Regulação para Baixo , Resistencia a Medicamentos Antineoplásicos , Oxaliplatina/farmacologia , Antracenos/farmacologia , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Neoplasias Colorretais/tratamento farmacológico , Flavonoides/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Inativação Gênica , Células HCT116 , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos
11.
Cancer Sci ; 110(5): 1609-1620, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30868675

RESUMO

Cancer tissues consist of cancer cells, surrounding stromal cells and the extracellular matrix. Cancer-associated fibroblasts (CAF) are one of the key components of stromal cells. CAF have a great impact on the behavior of cancer cells, including proliferation, invasion, metastasis and chemoresistance in many ways. However, the underlying mechanism had not been fully elucidated. In this study, we investigated the role of CAF in cisplatin resistance of lung cancer cells. By using conditioned medium from CAF (CAF-CM), we found that CAF decreased the sensitivity of lung cancer cells to cisplatin. RNA sequencing results showed that CAF expressed a higher level of Annexin A3 (ANXA3) than normal fibroblasts (NF), and CAF-CM incubation increased the ANXA3 level in lung cancer cells. Overexpression of ANXA3 in lung cancer cells increased cisplatin resistance and activated c-jun N-terminal kinase (JNK), whereas knockdown of ANXA3 increased cisplatin sensitivity. Further study showed that CAF-CM enhanced cisplatin resistance by inhibiting cisplatin-induced apoptosis, determined by repression of caspase-3 and caspase-8, through activation of the ANXA3/JNK pathway. Conversely, suppression of JNK activation by specific inhibitor retarded the effect of CAF-CM and ANXA3 on cisplatin sensitivity. Taken together, our study demonstrated that CAF potentiated chemoresistance of lung cancer cells through a novel ANXA3/JNK pathway both in vitro and in vivo, suggesting ANXA3 could be a potential therapeutic target for the treatment of chemoresistant cancer.


Assuntos
Anexina A3/genética , Fibroblastos Associados a Câncer/citologia , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/patologia , Células A549 , Animais , Anexina A3/metabolismo , Apoptose/efeitos dos fármacos , Fibroblastos Associados a Câncer/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Meios de Cultivo Condicionados/farmacologia , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Camundongos , Análise de Sequência de RNA/métodos , Células Tumorais Cultivadas , Regulação para Cima , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Eur Rev Med Pharmacol Sci ; 23(4): 1388-1396, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30840259

RESUMO

OBJECTIVE: The aim of this study was to investigate whether lnc00908 could affect the proliferative and migratory behaviors of ovarian cancer (OC) cells by regulating microRNA-495-5p, thus participating in the development of OC. PATIENTS AND METHODS: Quantitative Real Time-Polymerase Chain Reaction (QRT-PCR) was used to detect the expression levels of lnc00908 and microRNA-495-5p in OC tissues and normal ovarian tissues, as well as OC cell lines. The regulatory effects of lnc00908 and microRNA-495-5p on the proliferative and migration abilities of OC cells were detected by cell counting kit-8 (CCK-8) and transwell assay, respectively. The binding relationship between microRNA-495-5p and ANXA3, as well as miR-495-5p and lnc00908, was examined by luciferase reporter gene assay. Gain-of-function experiments were conducted to verify whether lnc00908 could affect the proliferative and migratory behaviors of OC cells by regulating microRNA-495-5p. RESULTS: Lnc00908 was highly expressed in OC tissues, and its expression was positively correlated with tumor stage. Overexpression of lnc00908 markedly promoted the proliferative and migratory abilities of SKOV3 and OVCAR cells. Luciferase reporter gene assay showed that lnc00908 could bind to microRNA-495-5p. However, microRNA-495-5p was significantly downregulated in OC tissues. Overexpression of microRNA-495-5p reversed the enhanced abilities of proliferation and migration in SKOV3 and OVCAR3 cells by lnc00908 overexpression. ANXA3 was a target gene of microRNA-495-5p. Moreover, overexpression of ANXA3 attenuated the inhibitory effect of miR-495-5p on the proliferative and migratory behaviors of SKOV3 and OVCAR3 cells. CONCLUSIONS: We found that the high expression of lnc00908 can promote the proliferation and migration abilities of OC cells through sponging microRNA-495-5p to regulate ANXA3 expression.


Assuntos
MicroRNAs/metabolismo , Neoplasias Ovarianas/patologia , RNA Longo não Codificante/metabolismo , Regiões 3' não Traduzidas , Anexina A3/química , Anexina A3/genética , Anexina A3/metabolismo , Área Sob a Curva , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/química , MicroRNAs/genética , Estadiamento de Neoplasias , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/mortalidade , Ovário/metabolismo , Ovário/patologia , RNA Longo não Codificante/genética , Curva ROC , Alinhamento de Sequência , Taxa de Sobrevida
13.
Mol Reprod Dev ; 86(5): 530-542, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30740829

RESUMO

Annexins are highly conserved and ubiquitous in various somatic cell types. They are involved in membrane transport and a range of calcium-regulated activities on the cell membrane surface, including vesicular transport, membrane fusion in exocytosis, signal transduction, and formation of calcium channels. They also regulate inflammatory response, cell differentiation, and interaction between cytoskeletal proteins. In this study, for the first time, an ANX3 gene from Artemia sinica ( As-anx3) was cloned. The As-anx3 full-length complementary DNA comprises 1,024 bp and has a 948 bp open reading frame encoding a 315-amino-acid polypeptide with four ANX domains. The profiles of both As-ANX3 mRNA and protein expression exhibited peaks at the 0 hr stage and had the same significant downregulation trend throughout the post-diapause embryo development stage. The ERK1/2, the phosphorylation levels of ERK1/2, and cell cycle-related protein (CDK4) expressions were analyzed by western blot analysis. The results showed that CDK4 presented a significantly ascending trend from 0 and 40 hr, although the phosphorylation levels of ERK1/2 did not increase significantly. The transcriptional and protein expressions of As-ANX3 were highly upregulated when the temperature was lowered from 25 to 15°C, but the expressions showed a gradual downward trend when the temperature was further lowered to 5°C. These results indicated that As-ANX3 plays a crucial role in restarting diapause and low-temperature stress in A. sinica.


Assuntos
Anexina A3/metabolismo , Resposta ao Choque Frio/fisiologia , Diapausa/fisiologia , Desenvolvimento Embrionário/fisiologia , Animais , Anexina A3/genética , Artemia , Temperatura Baixa , Embrião não Mamífero
15.
J Cell Physiol ; 234(7): 10535-10546, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-30456911

RESUMO

Acute myocardial infarction (AMI), as a severe consequence of coronary atherosclerotic heart disease, always contributes to the loss of myocardial cells. Mounting evidence shows that annexin protects the myocardium from ischemic injury. In this study, we examine the inhibition of annexin A3 (ANXA3) on AMI through the phosphatidylinositide 3-kinase/protein kinase B (PI3K/Akt) signaling pathway. We selected rats to build an AMI model which was then assigned into different groups. The hemodynamic parameters after transfection were detected by using enzyme-linked immunosorbent assay. The effect of silencing of ANXA3 on inflammatory reaction and the PI3K/Akt signaling pathway was assessed. Rats transfected with ANXA3-short hairpin RNA had alleviated hemodynamics, inflammatory reaction, decreased infarct size, α-smooth muscle actin, Collagen I, and Collagen III as well as an increased vascular endothelial growth factor. Silencing ANAX3 would promote repair and healing of myocardial tissue by activation of the PI3K/Akt signaling pathway. Collectively, our study provides evidence that the downregulation of ANXA3 promotes the repair and healing of myocardial tissues by activating the PI3K/Akt signaling pathway.


Assuntos
Anexina A3/genética , Inflamação/genética , Infarto do Miocárdio/genética , Miocárdio/metabolismo , Animais , Anexina A3/antagonistas & inibidores , Apoptose/genética , Biologia Computacional , Modelos Animais de Doenças , Inativação Gênica , Humanos , Inflamação/patologia , Infarto do Miocárdio/patologia , Miocárdio/patologia , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/patologia , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Transdução de Sinais/genética
16.
Clin Lab ; 64(9): 1517-1526, 2018 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30274024

RESUMO

BACKGROUND: The morbidity and mortality of lung cancer in Xuanwei (LCXW) is among the highest in China for both males and females and increases constantly. The underlying molecular changes associated with LCXW are still unclear. The purpose of this study was to screen out potential cancer-related genes which may become promising biomarkers of LCXW. METHODS: Differentially expressed genes (DEGs) were detected by the expression microarrays in 29 paired LCXW tissues (tumor tissue and matched adjacent non-cancerous lung tissues). Integrated with bioinformatic analyses, a literature review was applied for screening out important cancer-related genes. An additional 44 paired LCXW samples were collected to verify the transcription and expression levels of the candidate gene by qRT-PCR and Western blotting. The relationship between the candidate genes and clinical pathological features were evaluated using Fisher's test. RESULTS: mRNA expression microarrays revealed that the LCXW patients harbored 2,424 differentially expressed genes (fold change ≥ 2.0). Of these genes, 1,636 were up-regulated while the other 788 genes were down-regulated. Forty previously reported DNA repair genes associated with PAHs exposure were identified by microarrays. Bioinformatic analyses indicated down-regulated ANXA3 in LCXW patients which was closely related to pathological stage and involved in the regulation of a variety of biological responses. Review of the literature on ANXA3 found its down-regulation was a distinct expression pattern compared with lung cancer occurring in other geographic areas. qRT-PCR and Western blotting confirmed the down-regulation of ANXA3 was associated with LCXW. The correlation analysis of clinical features showed down-regulated ANXA3 was correlated to the progression of pathological stage. CONCLUSIONS: The LCXW patients harbored more DEGs, and these DEGs were involved in a wide range of pathways and biological function damage. We preliminarily suggested ANXA3 may be a potential LCXW related gene. ANXA3 may serve as a promising biomarker for diagnosis of LCXW.


Assuntos
Anexina A3/genética , Biomarcadores Tumorais/genética , Perfilação da Expressão Gênica/métodos , Neoplasias Pulmonares/genética , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , Transcriptoma , Adulto , China , Biologia Computacional , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Humanos , Neoplasias Pulmonares/mortalidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/terapia , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Fenótipo , Valor Preditivo dos Testes
17.
Pathol Res Pract ; 214(10): 1719-1725, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30236487

RESUMO

The following study investigated the effects of Annexin A3 (ANXA3) on breast cancer biological behavior in vivo, using nude mouse model bearing a subcutaneous tumor. A total of 18 female nude mice were randomly divided into three groups (n = 6): negative control group which was inoculated with MDA-MB-231 cells, blank control group which was inoculated with MDA-MB-231-NC cells, and the transfection group which was inoculated with MDA-MB-231-Sh cells. The experiment lasted for 4 weeks, during which mice conditions, diet and defecation were monitored on a daily basis. Body weight, as well as tumor diameters, which were assessed using standard caliper method, were measured once a week. In vivo imaging was performed to detect the activity of transplanted tumors. H&E staining was used to analyze the histological structure of tumor tissues in three groups, while flow cytometry and fluorescent RT-PCR were performed to measure cell proliferation and the expression of ANXA3 mRNA. Briefly, significantly slower tumor growth and tumor activity were observed in the transfection group compared to negative and blank controls, while the tumor weight and volume in this group were also significantly lower compared to the other two groups (P < 0.01). Sparse tumor cells accompanied with massive fibrous connective tissue proliferation, and lower new blood vessels formation were observed in transfection group compared to other groups. Moreover, mRNA and protein levels of ANXA3 were significantly lower in transfection group compared to the other two groups (P < 0.01). In addition, lower proliferation index and higher G0/1 cell count were observed in transfection group compared to negative and blank controls (P < 0.01). To sum up, these results suggested that ANXA3 silencing regulates the proliferation and inhibits the growth of MDA-MB-231 breast cancer cells. Consequently, ANXA3 might be used as a potential target for gene therapy in breast cancer.


Assuntos
Anexina A3/metabolismo , Neoplasias da Mama/patologia , Animais , Linhagem Celular Tumoral , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus
18.
Eur Rev Med Pharmacol Sci ; 22(15): 4837-4845, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30070320

RESUMO

OBJECTIVE: MicroRNAs (miRNAs) are increasingly recognized as oncogenes or tumor suppressors in colorectal cancer (CRC). The aim of this study was to explore the expression and functions of miR-340-5p in CRC. PATIENTS AND METHODS: The expression of miR-340-5p in CRC tissues and cell lines was detected by quantitative RT-PCR. Associations of miR-340-5p expression with clinicopathological factors and overall survival (OS) and progression-free survival (PFS) were statistically evaluated. Luciferase assay, RT-PCR, and Western blot were performed to verify the precise target of miR-340-5p. MTT assay, colony formation and transwell assay were performed to determine the proliferation, migration and invasion, respectively. RESULTS: Our results showed that miR-340-5p was significantly down-regulated in CRC tissues and cell lines, and was associated with histological grade (p=0.020), lymph nodes metastasis (p=0.003) and TNM stage (p=0.007). Furthermore, Kaplan-Meier and log-rank tests revealed that patients with low expression of miR-340-5p had a shorter OS (p=0.0110) and PFS (p=0.0032) than those with high expression of miR-340-5p. We further validated Annexin A3 (ANXA3) was a direct target of miR-340-5p in CRC. The functional assay showed that up-regulation of miR-340-5p or down-regulation of ANXA3 can both inhibit CRC cell proliferation, migration, and invasion. Besides, the re-expression of ANXA3 reversed the miR-340-5p induced suppression of cell proliferation, migration and invasion. CONCLUSIONS: Our data demonstrated that miR-340-5p exerted its tumor-suppressive function by directly targeting ANXA3 in CRC, suggesting that miR-340-5p might represent a novel prognostic biomarker and therapeutic target for CRC.


Assuntos
Anexina A3/biossíntese , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/metabolismo , MicroRNAs/biossíntese , Idoso , Anexina A3/antagonistas & inibidores , Anexina A3/genética , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Neoplasias Colorretais/genética , Regulação para Baixo/fisiologia , Feminino , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Prognóstico , Regulação para Cima/fisiologia
19.
J BUON ; 23(3): 713-719, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30003741

RESUMO

PURPOSE: To investigate the expression of ANXA3 in breast cancer tissues and normal breast tissues and its relationship with the clinicopathological features. METHODS: The expression levels of ANXA3 mRNA and protein were determined by fluorescent quantitative RT-PCR and Western blot, respectively, in 81 samples from breast cancer tissues and normal breast tissues. Flow cytometry, used to detect the cell cycle, further analyzed the differences in the cell proliferation indexes between cancer and the normal tissues. In addition, the correlation between the gene and protein expression levels of ANXA3 and the cell proliferation indexes in breast cancer tissues was calculated. RESULTS: The expression levels of ANXA3 mRNA and protein were significantly higher in breast cancer tissues than in control samples. Furthermore, their expression patterns were significantly different in patients with different axillary lymph node metastasis states, with or without vascular tumor thrombus, and with different molecular classifications. The expression of ANXA3 mRNA and protein in patients with triple-negative breast cancer was significantly higher than in Luminal A and B types. However, no significant differences were detected in the expression levels in other subtypes. Compared to normal tissues, the cell proliferation indexes of breast cancer tissues were significantly higher, and presented significant positive correlations with the ANXA3 gene and protein expression levels. CONCLUSION: The expression of ANXA3 might play a crucial role in promoting the occurrence, development, and metastasis of breast cancer. It could serve as an important marker involved in the invasion and metastasis states, and the prognosis of breast cancer.


Assuntos
Anexina A3/genética , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Axila/patologia , Ciclo Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Linfonodos/patologia , Metástase Linfática/genética , Metástase Linfática/patologia , Pessoa de Meia-Idade , Prognóstico , RNA Mensageiro/genética
20.
J Hepatol ; 69(4): 826-839, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29885413

RESUMO

BACKGROUND & AIMS: Advanced hepatocellular carcinoma (HCC) is a lethal malignancy with limited treatment options. Sorafenib is the only FDA-approved first-line targeted drug for advanced HCC, but its effect on patient survival is limited. Further, patients ultimately present with disease progression. A better understanding of the causes of sorafenib resistance, enhancing the efficacy of sorafenib and finding a reliable predictive biomarker are crucial to achieve efficient control of HCC. METHODS: The functional effects of ANXA3 in conferring sorafenib resistance to HCC cells were analyzed in apoptotic and tumorigenicity assays. The role of ANXA3/PKCδ-mediated p38 signaling, and subsequently altered autophagic and apoptotic events, was assessed by immunoprecipitation, immunoblotting, immunofluorescence and transmission electron microscopy assays. The prognostic value of ANXA3 in predicting response to sorafenib was evaluated by immunohistochemistry. The therapeutic value of targeting ANXA3 to combat HCC with anti-ANXA3 monoclonal antibody alone or in combination with sorafenib/regorafenib was investigated ex vivo and in vivo. RESULTS: ANXA3 conferred HCC cells with resistance to sorafenib. ANXA3 was found enriched in sorafenib-resistant HCC cells and patient-derived xenografts. Mechanistically, overexpression of ANXA3 in sorafenib-resistant HCC cells suppressed PKCδ/p38 associated apoptosis and activated autophagy for cell survival. Clinically, ANXA3 expression correlated positively with the autophagic marker LC3B in HCC and was associated with a worse overall survival in patients who went on to receive sorafenib treatment. Anti-ANXA3 monoclonal antibody therapy combined with sorafenib/regorafenib impaired tumor growth in vivo and significantly increased survival. CONCLUSION: Anti-ANXA3 therapy in combination with sorafenib/regorafenib represents a novel therapeutic strategy for HCC treatment. ANXA3 represents a useful predictive biomarker to stratify patients with HCC for sorafenib treatment. LAY SUMMARY: This study represents the most extensive pre-clinical characterization of anti-ANXA3 monoclonal antibodies for the treatment of hepatocellular carcinoma to date. These results support the clinical trial development of anti-ANXA3 antibodies in combination with sorafenib/regorafenib. Further studies will optimize patient target selection and identify the best treatment combinations.


Assuntos
Anexina A3/antagonistas & inibidores , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Compostos de Fenilureia/uso terapêutico , Piridinas/uso terapêutico , Sorafenibe/uso terapêutico , Animais , Anticorpos Monoclonais/uso terapêutico , Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Carcinoma Hepatocelular/patologia , Resistencia a Medicamentos Antineoplásicos , Células Hep G2 , Humanos , Neoplasias Hepáticas/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Ensaios Antitumorais Modelo de Xenoenxerto , Proteínas Quinases p38 Ativadas por Mitógeno/fisiologia
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