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1.
Sensors (Basel) ; 21(16)2021 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-34450980

RESUMO

Copper (II) ions have been shown to greatly improve the chemical stability and peroxidase-like activity of gold nanoclusters (AuNCs). Since the affinity between Cu2+ and pyrophosphate (PPi) is higher than that between Cu2+ and AuNCs, the catalytic activity of AuNCs-Cu2+ decreases with the introduction of PPi. Based on this principle, a new colorimetric detection method of PPi with high sensitivity and selectivity was developed by using AuNCs-Cu2+ as a probe. Under optimized conditions, the detection limit of PPi was 0.49 nM with a linear range of 0.51 to 30,000 nM. The sensitivity of the method was three orders of magnitude higher than that of a fluorescence method using AuNCs-Cu2+ as the probe. Finally, the AuNCs-Cu2+ system was successfully applied to directly determine the concentration of PPi in human urine samples.


Assuntos
Ouro , Nanopartículas Metálicas , Colorimetria , Cobre , Difosfatos , Corantes Fluorescentes , Humanos , Limite de Detecção , Peroxidase , Peroxidases , Espectrometria de Fluorescência
2.
Front Immunol ; 12: 677730, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34305907

RESUMO

Ichthyophthirius multifiliis is a major pathogen that causes a high mortality rate in trout farms. However, systemic responses to the pathogen and its interactions with multiple organs during the course of infection have not been well described. In this study, dual-organ transcriptomic responses in the liver and head kidney and hemato-serological indexes were profiled under I. multifiliis infection and recovery to investigate systemic immuno-physiological characteristics. Several strategies for massive transcriptomic interpretation, such as differentially expressed genes (DEGs), Poisson linear discriminant (PLDA), and weighted gene co-expression network analysis (WGCNA) models were used to investigate the featured genes/pathways while minimizing the disadvantages of individual methods. During the course of infection, 6,097 and 2,931 DEGs were identified in the head kidney and liver, respectively. Markers of protein processing in the endoplasmic reticulum, oxidative phosphorylation, and the proteasome were highly expressed. Likewise, simultaneous ferroptosis and cellular reconstruction was observed, which is strongly linked to multiple organ dysfunction. In contrast, pathways relevant to cellular replication were up-regulated in only the head kidney, while endocytosis- and phagosome-related pathways were notably expressed in the liver. Moreover, interestingly, most immune-relevant pathways (e.g., leukocyte trans-endothelial migration, Fc gamma R-mediated phagocytosis) were highly activated in the liver, but the same pathways in the head kidney were down-regulated. These conflicting results from different organs suggest that interpretation of co-expression among organs is crucial for profiling of systemic responses during infection. The dual-organ transcriptomics approaches presented in this study will greatly contribute to our understanding of multi-organ interactions under I. multifiliis infection from a broader perspective.

3.
Hum Mol Genet ; 30(21): 1932-1940, 2021 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-34132789

RESUMO

Rheumatoid arthritis (RA) is associated with increased localized and generalized bone loss, but the complex genetic mechanism between them is still unknown. By leveraging large-scale genome-wide association studies summary statistics and individual-level datasets (i.e. UK Biobank), a series of genetic approaches were conducted. Linkage disequilibrium score regression reveals a shared genetic correlation between RA and estimated bone mineral density (eBMD) (rg = -0.059, P = 0.005). The PLACO analysis has identified 74 lead (8 novel) pleiotropic loci that could be mapped to 99 genes, the genetic functions of which reveal the possible mechanism underlying RA and osteoporosis. In European, genetic risk score (GRS) and comprehensive Mendelian randomization (MR) were utilized to evaluate the causal association between RA and osteoporosis in European and Asian. The increase in GRS of RA could lead to a decrease of eBMD (beta = -0.008, P = 3.77E-6) and a higher risk of facture [odds ratio (OR) = 1.012, P = 0.044]. MR analysis identified that genetically determined RA was causally associated with eBMD (beta = -0.021, P = 4.14E-05) and fracture risk (OR = 1.036, P = 0.004). Similar results were also observed in Asian that osteoporosis risk could be causally increased by RA (OR = 1.130, P = 1.04E-03) as well as antibodies against citrullinated proteins-positive RA (OR = 1.083, P = 0.015). Overall, our study reveals complex genetic mechanism between RA and osteoporosis and provides strong evidence for crucial role of RA in pathogenesis of osteoporosis.

4.
Respir Res ; 22(1): 42, 2021 Feb 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549109

RESUMO

Alveolar epithelial cells play an essential role in the initiation and progression of pulmonary fibrosis, and the occurrence of epithelial-mesenchymal transition (EMT) may be the early events of pulmonary fibrosis. Recent studies have shown chemokines are involved in the complex process of EMT, and CXC chemokine ligand 16 (CXCL16) is also associated with many fibrosis-related diseases. However, whether CXCL16 is dysregulated in alveolar epithelial cells and the role of CXCL16 in modulating EMT in pulmonary fibrosis has not been reported. In this study, we found that CXCL16 and its receptor C-X-C motif chemokine receptor 6 (CXCR6) were upregulated in bleomycin induced EMT in human alveolar type II-like epithelial A549 cells. Synergistic effect of CXCL16 and bleomycin in promoting EMT occurrence, extracellular matrix (ECM) excretion, as well as the pro-inflammatory and pro-fibrotic cytokines productions in A549 cells were observed, and those biological functions were impaired by CXCL16 siRNA. We further confirmed that CXCL16 regulated EMT in A549 cells via the TGF-ß1/Smad3 pathways. These results indicated that CXCL16 could promote pulmonary fibrosis by promoting the process of EMT via the TGF-ß1/Smad3 signaling pathway.

6.
Cell Death Dis ; 11(8): 612, 2020 08 13.
Artigo em Inglês | MEDLINE | ID: mdl-32792505

RESUMO

Intervertebral disc degeneration (IDD) is the most common degenerative disease all over the word. Our previous study confirmed that the downregulated circ-GRB10 directly interacts with miR-328-5p, which modulate ERBB2 and leads to the degeneration of intervertebral disc; however, the underpinning mechanism of circ-GRB10 dysregulation remains unclear. We identified that FUS and demonstrated that circ-GBR10 biosynthesis in nucleus pulposus (NP) cells was promoted by FUS, whose expression was controlled by miR-141-3p. In addition, ERBB2 downregulation led to decreased Erk1/2 phosphorylation which enhanced miR-141-3p production in NP cells. In vivo data indicated that circ-GRB10 inhibited IDD in rat model. The present study revealed that miR-141-3p and FUS are key factors that regulate circ-GRB10 synthesis in NP cells. In addition, circ-GBR10 participates in the molecular circuitry that controls human IDD development. These findings provide a basis for further functional, diagnostic and therapeutic studies of circ-GRB10 in IDD.


Assuntos
Redes Reguladoras de Genes , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/patologia , RNA Circular/metabolismo , Adulto , Animais , Sequência de Bases , Modelos Animais de Doenças , Feminino , Humanos , Sistema de Sinalização das MAP Quinases , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Fosforilação , Precursores de RNA/genética , Precursores de RNA/metabolismo , RNA Circular/genética , Proteína FUS de Ligação a RNA/metabolismo , Ratos Sprague-Dawley , Receptor ErbB-2/metabolismo
7.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 28(4): 1251-1255, 2020 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-32798407

RESUMO

OBJECTIVE: To investigate the influence of influence of combination with 1q21 amplification or-no in patients with newly diagnosed MM on the clinical effecacy of bortezomib-based induction chemotherapy and long-term prognosis of patients. METHODS: 148 patients with newly diagnosed MM treated from January 2010 to May 2018 were selected and divided into 2 groups: group A (70 patients) without 1q21 amplification and group B (78 patients) with 1q21 amplification; and the survival benefit and influence on clinical efficacy of bortezomib were compared between 2 groups, and the factors influencing clinical prognosis in the patients with newly diagnosed MM were analyzed. RESULTS: The median PFS and OS of patients in B group were significantly shorter than those in group A (P<0.05). There was no significant difference in the median OS and PFS between patients with 1q21 amplification copies number =3 and >3 (P>0.05). Multivariate Cox model analysis indicated that the adverse factors for OS were ISS staging, Hb levels, ß2 microglobulin levels and 1q21 amplification respectively, and the adverse factors for PFS were Hb levels and 1q21 amplification respectively in patients with newly diagnosed MM (P<0.05). The very good partial remission rate of newly diagnosed MM patients with 1q21 amplification and bortezomib-based induction chemotherapy were significantly higher than that in the patients without bortezomib-based induction chemotherapy (P<0.05). The median PFS time of newly diagnosed MM patients with 1q21 amplification and auto-HSCT after bortezomib-based induction chemotherapy was significantly longer than that of patients without auto-HSCT (P<0.05). CONCLUSION: 1q21 amplification should be the independent risk factor for poor prognosis of patients with newly treated MM. The application of bortezomib-containing induction chemotherapy in patients with 1q21 amplification can efficiently improve the remission rate, while auto-HSCT consolidation therapy may prolong patients' PFS.


Assuntos
Quimioterapia de Indução , Mieloma Múltiplo/tratamento farmacológico , Protocolos de Quimioterapia Combinada Antineoplásica , Bortezomib/uso terapêutico , Intervalo Livre de Doença , Humanos , Prognóstico , Estudos Retrospectivos , Resultado do Tratamento
8.
Animals (Basel) ; 10(9)2020 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-32854279

RESUMO

Although over-nutrition from overfeeding-induced obesity is known to be highly associated with metabolic and immunological disorders in humans, little is known about overfeeding-induced obesity in fish farming. The purpose of this study was to investigate changes in immuno-physiological parameters, to better understand the potential risk of overfeeding-induced obesity in fish. Commercial feed was provided to fish in the overfed group until they refuse to eat, but fish in the control group was fed with the feed at 1% bodyweight per day. The hemato-serological, histological, and immunological changes were observed at weeks 2 and 8. Rainbow trout leukocytes were co-incubated with oxidized low-density lipoprotein (OxLDL), and the phagocytes engulfing the OxLDL and the presence of apoptotic cells were evaluated. The body weight, body mass index (BMI), and hepatosomatic index (HSI) index were significantly higher in the overfed group, and high lipid accumulation and fatty changes were also observed in their livers, indicating that the feeding regime used in this study led to overfeeding-induced obesity. Likewise, much higher numbers of and larger vacuoles were observed in overfed fish macrophages, showing unclear boundaries between the cytoplasm and extracellular space. In the overfed group, the expression of IL-10, HSP70, TLR2, and CD36 was significantly higher, and lymphocyte apoptosis was more evident, indicating that overfeeding-induced obese fish might have immunologic disorders. This was the first study to demonstrate that overfeeding-induced obesity could cause an immune-physiological imbalance in rainbow trout, making them more vulnerable to infectious diseases and various stressful conditions. This study will contribute to improvements in fish nutrition, feeding practices, fish nutrition, and disease prevention in the aquaculture industry.

9.
Int J Mol Med ; 46(2): 621-632, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32626912

RESUMO

Intervertebral disc degeneration (IDD) is an important cause of lower back pain, although the underlying mechanisms remain poorly understood. The present study aimed to examine the role of a circular RNA derived from tissue inhibitor of metallopeptidases 2 (circ­TIMP2) in degenerative nucleus pulposus (NP) tissues, and to validate its function in cultured human NP cells. Overexpression of miR­185­5p in NP cells markedly inhibited the enhanced extracellular matrix (ECM) catabolism induced by tumor necrosis factor­α (TNF­α) and interleukin­1ß (IL­1ß) treatment. Bioinformatics analysis demonstrated that matrix metalloproteinase 2 (MMP2) was a potential target of miR­185­5p. MMP2 protein expression levels were increased following treatment with TNF­α and IL­1ß in NP cells compared with those in untreated cells, and this effect was attenuated by transfection with miR­185­5p. Compared with normal NP tissues, IDD samples exhibited higher circ­TIMP2 expression levels. In addition, overexpression of circ­TIMP2 promoted ECM catabolism and suppressed ECM anabolism. Furthermore, circ­TIMP2 sequestered miR­185­5p, which may potentially upregulate the target genes associated with ECM degradation. In conclusion, the results of the present study revealed that circ­TIMP2 promoted TNF­α­ and IL­1ß­induced NP cell imbalance between ECM anabolism and catabolism via miR­185­5p­MMP2 signaling. These findings provide a potential therapeutic option for the treatment of IDD.


Assuntos
Metaloproteinase 2 da Matriz/metabolismo , Núcleo Pulposo/metabolismo , Adulto , Northern Blotting , Western Blotting , Biologia Computacional , Feminino , Humanos , Imunoprecipitação , Hibridização in Situ Fluorescente , Degeneração do Disco Intervertebral/metabolismo , Masculino , Metaloproteinase 2 da Matriz/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Transdução de Sinais/fisiologia
10.
J Fish Dis ; 43(9): 1029-1037, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32627213

RESUMO

Although Carnobacterium maltaromaticum has been used as a probiotic in fish, it was reported to cause disease for the first time in Korea. The objective of this study was to understand the differences between pathogenic and non-pathogenic strains. Pathogenicity was tested by challenging rainbow trout with C. maltaromaticum ATCC35586 and 18ISCm isolated from diseased fish, and DSM20342 isolated from a dairy product. We also compared 24 genomes of C. maltaromaticum strains plus the genome of our isolate 18ISCm sequenced in this study. Only the strains from diseased fish caused high mortality with severe histopathological changes. Although all strains shared more than 90% of Ko_id, wecC and xtmA were found only in strains from diseased fish. Interestingly, only strains from diseased fish harboured two wecC paralogs involved in the production of D-mannosaminuronic acid which is a major component of a well-known virulence factor, teichuronic acid. Two wecC paralogs of 18ISCm were increased when they were co-cultured with trout blood cells, suggesting that wecC genes might play a role in virulence. The results of this study show that strains isolated from diseased fish are different from strains derived from food in terms of pathogenicity to fish and the presence of virulence-related genes.


Assuntos
Carnobacterium/genética , Carnobacterium/patogenicidade , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Positivas/veterinária , Virulência/genética , Animais , Aquicultura , Genoma Bacteriano , Infecções por Bactérias Gram-Positivas/microbiologia , Oncorhynchus mykiss , República da Coreia
11.
Cell Death Dis ; 11(5): 315, 2020 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-32366862

RESUMO

Intervertebral disc degeneration (IDD) is an important factor leading to low back pain, although the underlying mechanisms remain poorly understood. In this study we examined the role of circular RNA FAM169A (circ-FAM169A) in degenerative nucleus pulposus (NP) tissues, and validated its function in cultured human NP cells. Overexpression of circ-FAM169A in NP cells markedly enhanced extracellular matrix (ECM) catabolism and suppressed ECM anabolism in NP cells. Furthermore, circ-FAM169A sequestered miR-583, which could potentially upregulate BTRC, an inducer of the NF-κB signaling pathway. In conclusion, the present study revealed that circ-FAM169A promotes IDD development via miR-583/BTRC signaling. These findings provide a potential therapeutic option for the treatment of IDD.


Assuntos
Degeneração do Disco Intervertebral/genética , MicroRNAs/metabolismo , RNA Circular/metabolismo , Proteínas Contendo Repetições de beta-Transducina/metabolismo , Adulto , Animais , Sequência de Bases , Modelos Animais de Doenças , Matriz Extracelular/metabolismo , Feminino , Perfilação da Expressão Gênica , Inativação Gênica , Humanos , Degeneração do Disco Intervertebral/diagnóstico por imagem , Masculino , MicroRNAs/genética , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Análise de Componente Principal , RNA Circular/genética , Ratos Sprague-Dawley , Transdução de Sinais , Regulação para Cima/genética
12.
Mol Med Rep ; 21(6): 2321-2334, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32323806

RESUMO

Baicalin is an important flavonoid compound THAT is isolated from the Scutellaria baicalensis Georgi Chinese herb and plays a critical role in anti­oxidative, anti­inflammatory, anti­infection and anti­tumor functions. Although baicalin can suppress the proliferation of tumor cells, the underlying mechanisms of baicalin in bleomycin (BLM)­induced pulmonary fibrosis remain to be elucidated. Thus, the aim of the present study was to determine the role of baicalin in pulmonary fibrosis and fibroblast proliferation in rats. Hematoxylin and eosin (H&E) and Masson staining were used to measure the morphology of pulmonary fibrosis, ELIASA kits were used to test the ROS and inflammation, and western blotting and TUNEL were performed to study the apoptosis proteins. In vitro, MTT assay, flow cytometry, western blotting and immunofluorescence were performed to investigate the effects of baicalin on proliferation of fibroblasts. The most significantly fibrotic changes were identified in the lungs of model rats at day 28. Baicalin (50 mg/kg) attenuated the degree of pulmonary fibrosis, and the hydroxyproline content of the lung tissues was decreased in the baicalin group, compared with the BLM group. Further investigation revealed that baicalin significantly increased glutathione peroxidase (GSH­px), total­superoxide dismutase (T­SOD) and glutathione (GSH) levels, whilst decreasing that of serum malondialdehyde (MDA). TUNEL­positive cells were significantly decreased in rats treated with baicalin group, compared with the model group. Furthermore, it was found that BLM promoted fibroblasts viability in a dose­dependent manner in vivo, which was restricted following treatment with different concentrations of baicalin. Moreover, BLM promoted the expression levels of cyclin A, D and E, proliferating cell nuclear antigen, phosphorylated (p)­AKT and p­calcium/calmodulin­dependent protein kinase type. BLM also promoted the transition of cells from the G0/G1 phase to the G2/M and S phases, and increased the intracellular Ca2+ concentration, which was subsequently suppressed by baicalin. Collectively, the results of the present study suggested that baicalin exerted a suppressive effect on BLM­induced pulmonary fibrosis and fibroblast proliferation.


Assuntos
Flavonoides/farmacologia , Fibrose Pulmonar/patologia , Transdução de Sinais/efeitos dos fármacos , Animais , Bleomicina/toxicidade , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Feminino , Fibroblastos/citologia , Fibroblastos/metabolismo , Flavonoides/uso terapêutico , Regulação da Expressão Gênica/efeitos dos fármacos , Hidroxiprolina/metabolismo , Pulmão/patologia , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/tratamento farmacológico , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo
13.
Int J Biol Sci ; 16(8): 1388-1402, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32210727

RESUMO

Objective: The therapeutic effects of the checkpoint kinase 1 (CHK1)-targeted inhibition in tumor therapy have been confirmed, but how to choose an effective application method in breast cancer with heterogeneous molecular characteristics has remained unclear. Methods: We evaluated the status of CHK1 in breast cancer using the cancer genome atlas database. Chemosensitivity and single-agent antitumor activity of CHK1 inhibition were measured by drug sensitivity assay, cell proliferation assay, cell cycle and apoptosis analysis in breast cancer with different ER/PR status. And based on the conjoint transcriptome atlas analyses, the corresponding mechanism were explored. Results: In ER-/PR-/HER2- breast cancer, CHK1 inhibition enhanced adriamycin (ADR) chemosensitivity which was mediated by the mitotic checkpoint complex (MCC)-anaphase-promoting complex/cyclosome (APC/C)-cyclin B1 axis, Msh homeobox 2 (MSX2) and Bcl-2-like protein 11 (BIM). However, in ER+/PR+/HER2- breast cancer, because of the significant suppression for centromere protein F (CENPF)-mediated transcriptional activation of CHK1 induced by ADR itself, CHK1 inhibition fails to sensitize ADR toxicity. Interestingly, CHK1 inhibition showed the single-agent antitumor activity in ER+/PR+/HER2- breast cancer which was mediated by the cyclin dependent kinase inhibitor 1A (p21), kinesin family member 11 (Eg5) and cell surface death receptor (Fas). Conclusions: CHK1's variable role determines the application of CHK1 inhibition in breast cancer with ER/PR heterogeneity.

14.
Oncogenesis ; 8(5): 30, 2019 Apr 18.
Artigo em Inglês | MEDLINE | ID: mdl-31000690

RESUMO

Breast cancer ranks no. 1 in women cancer worldwide, while 60-70% are estrogen receptor alpha positive. The estrogen selective modulators, such as tamoxifen, become the effective drugs for controlling ER alpha breast cancer progression. However, tamoxifen resistance will develop during long-time treatment and cancer progression. Thus, further understanding of ER alpha signaling becomes necessary for the improvement of breast cancer therapy. Here, we identify TRIM56 as a novel regulatory factor in ER alpha signaling. TRIM56 expression is positively correlated with ER alpha and PR in breast cancer samples and is related to poor prognosis in endocrine therapy patients. TRIM56 depletion significantly decreases ER alpha signaling activity and ER-alpha-positive breast cancer proliferation in vitro and in vivo. TRIM56 associates with AF1 domain of ER alpha via its WD40 domain in the cytoplasm. TRIM56 prolongs ER alpha protein stability, possibly through targeting ER alpha K63-linked ubiquitination. In conclusion, our study reveals an interesting posttranslational mechanism between TRIM56 and ER alpha in breast cancer progression. Targeting TRIM56 could be a promising approach for ER-alpha-positive breast cancer.

15.
J Cell Mol Med ; 22(12): 6077-6086, 2018 12.
Artigo em Inglês | MEDLINE | ID: mdl-30334368

RESUMO

Oestrogen receptor α (ERα) is overexpressed in two-thirds of all breast cancer cases and is involved in breast cancer development and progression. Although ERα -positive breast cancer can be effectively treated by endocrine therapy, endocrine resistance is an urgent clinical problem. Thus, further understanding of the underlying mechanisms involved in ERα signalling is critical in dealing with endocrine resistance in patients with breast cancer. In the present study, unbiased RNA sequence analysis was conducted between the MCF-7 and MCF-7 tamoxifen-resistant (LCC2) cell lines in order to identify differentially expressed genes. The whole transcriptomic data indicated that the JAK-STAT pathway is markedly up-regulated, particularly the ISGF3 complex. As the critical effectors, STAT1 and IRF9 were up-regulated 5- and 20-fold, respectively, in LCC2 cells. The biological experiments indicated that STAT1 is important for ERα signalling. Depletion of STAT1 or inhibition of STAT1 function significantly decreased levels of ERα protein, ERα -target gene expression and cell proliferation in both the MCF-7 and LCC2 cell lines. Chromatin immunoprecipitation revealed that ERα transcription is associated with STAT1 recruitment to the ERα promoter region, suggesting that transcriptional regulation is one mechanism by which STAT1 regulates ERα mRNA levels and ERα signalling in breast cancer cells. The present study reveals a possible endocrine-resistant mechanism by which STAT1 modulates ERα signalling and confers tamoxifen resistance. Targeting of STAT1 is a potential treatment strategy for endocrine-resistant breast cancers.


Assuntos
Neoplasias da Mama/genética , Receptor alfa de Estrogênio/genética , Fator de Transcrição STAT1/genética , Transcrição Genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Fator Gênico 3 Estimulado por Interferon, Subunidade alfa/genética , Células MCF-7 , Transdução de Sinais/efeitos dos fármacos , Tamoxifeno/farmacologia
16.
Oncol Lett ; 16(4): 4984-4996, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30250564

RESUMO

As a clinically heterogeneous subtype of breast cancer, triple-negative breast cancer (TNBC) is associated with a poor clinical outcome and a high relapse rate. Conventional chemotherapy and radiotherapy are effective treatments for patients with TNBC. However, the prognosis of TNBC remains unsatisfactory. Therefore, a large volume of research has explored the molecular markers and oncogenic signaling pathways associated with TNBC, including the cell cycle, DNA damage response and androgen receptor (AR) signaling pathways, to identify more efficient targeted therapies. However, whether these predicted pathways are effective targets has yet to be confirmed. In the present review, potentially carcinogenic signaling pathways in TNBCs from previous reports were considered, and ultimately five tumorigenic signaling pathways were selected, specifically receptor tyrosine kinases and downstream signaling pathways, the epithelial-to-mesenchymal transition and associated pathways, the immunoregulatory tumor microenvironment, DNA damage repair pathways, and AR and coordinating pathways. The conclusions of the preclinical and clinical trials of each pathway were then consolidated. Although a number of signaling pathways in TNBC have been considered in preclinical and clinical trials, the aforementioned pathways account for the majority of the malignant behaviors of TNBC. Identifying the alterations to different carcinogenic signaling pathways and their association with the heterogeneity of TNBC may facilitate the development of optimal precision medical approaches for patients with TNBC, potentially improving the efficiency of anticancer therapy.

18.
Hum Mutat ; 39(10): 1442-1455, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30039884

RESUMO

In this study, a customized amplicon-based target sequencing panel was designed to enrich the whole exon regions of six genes associated with the risk of breast cancer. Targeted next-generation sequencing (NGS) was performed for 146 breast cancer patients (BC), 71 healthy women with a family history of breast cancer (high risk), and 55 healthy women without a family history of cancer (control). Sixteen possible disease-causing mutations on four genes were identified in 20 samples. The percentages of possible disease-causing mutation carriers in the BC group (8.9%) and in the high-risk group (8.5%) were higher than that in the control group (1.8%). The BRCA1 possible disease-causing mutation group had a higher prevalence in family history and triple-negative breast cancer, while the BRCA2 possible disease-causing mutation group was younger and more likely to develop axillary lymph node metastasis (P < 0.05). Among the 146 patients, 47 with a family history of breast cancer were also sequenced with another 14 moderate-risk genes. Three additional possible disease-causing mutations were found on PALB2, CHEK2, and PMS2 genes, respectively. The results demonstrate that the six-gene targeted NGS panel may provide an approach to assess the genetic risk of breast cancer and predict the clinical prognosis of breast cancer patients.


Assuntos
Neoplasias da Mama/genética , Predisposição Genética para Doença , Mutação em Linhagem Germinativa , Oncogenes , Adulto , Neoplasias da Mama/patologia , Estudos de Casos e Controles , Quinase do Ponto de Checagem 2/genética , Biologia Computacional/métodos , Éxons , Proteína do Grupo de Complementação N da Anemia de Fanconi/genética , Feminino , Genes BRCA1 , Genes BRCA2 , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Pessoa de Meia-Idade , Endonuclease PMS2 de Reparo de Erro de Pareamento/genética , Anotação de Sequência Molecular , Gradação de Tumores , Estadiamento de Neoplasias , Reprodutibilidade dos Testes , Análise de Sequência de DNA , Adulto Jovem
19.
Cell Physiol Biochem ; 45(6): 2506-2515, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29554650

RESUMO

BACKGROUND/AIMS: Low back pain has become one of the most common musculoskeletal diseases in the world. Studies have shown that intervertebral disc degeneration (IDD) is an important factor leading to low back pain, but the mechanisms underlying IDD remain largely unknown. Research over the past decade has suggested critical roles for microRNAs (miRNAs) in natural growth and disease progression. However, it remains poorly understood whether circular RNAs participate in IDD. METHODS: Clinical IDD samples were collected from 20 patients who underwent discectomy. Weighted gene co-expression network analysis was used to identify the co-expression miRNA network modules (highly co-expressed clusters of miRNAs) that were associated with IDD grade. RESULTS: miR-3150a-3p was the most significantly up-regulated miRNA in module "Blue." Notably, aggrecan (ACAN) was identified as a direct target gene of miR-3150a-3p and ACAN expression was regulated by miR-3150a-3p. Overexpression of miR-3150a-3p decreased ACAN expression in nucleus pulposus cells, whereas inhibition of miR-3150a-3p increased ACAN expression. In addition, ACAN expression was negatively correlated with IDD grade. CONCLUSION: Our study suggests that the reduction of ACAN expression induced by the upregulation of miR-3150a-3p might participate in the development of IDD.


Assuntos
Agrecanas/genética , Degeneração do Disco Intervertebral/genética , MicroRNAs/metabolismo , Adulto , Regulação para Baixo , Feminino , Humanos , Degeneração do Disco Intervertebral/patologia , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Regulação para Cima
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