RESUMO
Cell death can be executed through distinct subroutines. PANoptosis is a unique inflammatory cell death modality involving the interactions between pyroptosis, apoptosis, and necroptosis, which can be mediated by multifaceted PANoptosome complexes assembled via integrating components from other cell death modalities. There is growing interest in the process and function of PANoptosis. Accumulating evidence suggests that PANoptosis occurs under diverse stimuli, for example, viral or bacterial infection, cytokine storm, and cancer. Given the impact of PANoptosis across the disease spectrum, this review briefly describes the relationships between pyroptosis, apoptosis, and necroptosis, highlights the key molecules in PANoptosome formation and PANoptosis activation, and outlines the multifaceted roles of PANoptosis in diseases together with a potential for therapeutic targeting. We also discuss important concepts and pressing issues for future PANoptosis research. Improved understanding of PANoptosis and its mechanisms is crucial for identifying novel therapeutic targets and strategies.
Assuntos
Apoptose , Piroptose , Humanos , Morte Celular , Síndrome da Liberação de Citocina , BiologiaRESUMO
BAG3 is constitutively expressed in multiple types of cancer cells and its high expression is associated with tumour progression and poor prognosis of PDAC. However, little is known about the role of BAG3 in the regulation of stromal microenvironment of PDAC. The current study demonstrated that beside PDAC tumour cells, BAG3 was also expressed in some activated stroma cells in PDAC tissue, as well as in activated PSCs. In addition, the current study demonstrated that BAG3 expression in PSCs was involved in maintenance of PSCs activation and promotion of PDACs invasion via releasing multiple cytokines. The current study demonstrated that BAG3-positive PSCs promoted invasion of PDACs via IL-8, MCP1, TGF-ß2 and IGFBP2 in a paracrine manner. Furthermore, BAG3 sustained PSCs activation through IL-6, TGF-ß2 and IGFBP2 in an autocrine manner. Thereby, the current study provides a new insight into the involvement of BAG3 in remodelling of stromal microenvironment favourable for malignant progression of PDAC, indicating that BAG3 might serve as a potential target for anti-fibrosis of PDAC.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Ductal Pancreático/metabolismo , Neoplasias Pancreáticas/metabolismo , Células Estreladas do Pâncreas/metabolismo , Microambiente Tumoral/genética , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Reguladoras de Apoptose/genética , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Citocinas/metabolismo , Humanos , Imuno-Histoquímica , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/genética , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Interleucina-8/genética , Interleucina-8/metabolismo , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/patologia , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismoRESUMO
Ovarian cancer is commonly treated with cisplatin and paclitaxel combination chemotherapy; however, ovarian cancer cells often develop resistance to these drugs. Increasingly, microRNAs (miRNAs) including miR-873 have been implicated in drug resistance in many cancers, but the role of miR-873 in ovarian cancer remains unknown. MTT cell viability assays revealed that the sensitivities of ovarian cancer lines to cisplatin and paclitaxel increased following transfection with miR-873 (P < 0.05). After predicting the miR-873 binding region in the 3'-untranslated region of ABCB1, dual-luciferase reporter assay confirmed this prediction. RT-PCR and Western blotting revealed that MDR1 expression was significantly downregulated after transfection with miR-873 and upregulated after transfection with anti-miR-873 at both mRNA and protein levels compared to negative controls (P < 0.05). Experiments in a mouse xenograft model confirmed that intratumoral administration of miR-873 could enhance the efficacy of cisplatin in inhibiting tumor growth in ovarian cancer in vivo (P < 0.05). ABCB1 overexpression reduced sensitivities of ovarian cancer lines OVCAR3 and A2780 to cisplatin and paclitaxel, which can be reversed by miR-873 mimic transfection (P < 0.05). In summary, we demonstrated that overexpression of miR-873 increased the sensitivity of ovarian cancer cells to cisplatin and paclitaxel by targeting MDR1 expression. Our findings suggest that combination therapies with chemotherapy agents and miR-873 may suppress drug resistance in ovarian cancer.
Assuntos
Cistadenocarcinoma/metabolismo , MicroRNAs/genética , Proteínas de Neoplasias/fisiologia , Neoplasias Ovarianas/metabolismo , RNA Neoplásico/genética , Regiões 3' não Traduzidas/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/biossíntese , Subfamília B de Transportador de Cassetes de Ligação de ATP/genética , Subfamília B de Transportador de Cassetes de Ligação de ATP/fisiologia , Animais , Antineoplásicos Alquilantes/uso terapêutico , Antineoplásicos Fitogênicos/farmacocinética , Antineoplásicos Fitogênicos/farmacologia , Linhagem Celular Tumoral , Cisplatino/farmacocinética , Cisplatino/uso terapêutico , Cistadenocarcinoma/tratamento farmacológico , Cistadenocarcinoma/genética , Cistadenocarcinoma/patologia , Resistência a Múltiplos Medicamentos/genética , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Xenoenxertos , Humanos , Camundongos , Camundongos Nus , MicroRNAs/antagonistas & inibidores , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Paclitaxel/farmacocinética , Paclitaxel/farmacologia , RNA Antissenso/genética , RNA Mensageiro/biossíntese , RNA Neoplásico/antagonistas & inibidores , RNA Neoplásico/biossíntese , Distribuição Aleatória , TransfecçãoRESUMO
Cancer metastasis is a complex process influenced by various factors, including epithelial-mesenchymal transition (EMT), tumor cell proliferation, tumor microenvironment, and cellular metabolic status, which remains a significant challenge in clinical oncology, accounting for a majority of cancer-related deaths. TEAD4, a key mediator of the Hippo signaling pathway, has been implicated in regulating these factors that are all critical in the metastatic cascade. TEAD4 drives tumor metastasis and chemoresistance, and its upregulation is associated with poor prognosis in many types of cancers, making it an attractive target for therapeutic intervention. TEAD4 promotes EMT by interacting with coactivators and activating the transcription of genes involved in mesenchymal cell characteristics and extracellular matrix remodeling. Additionally, TEAD4 enhances the stemness of cancer stem cells (CSCs) by regulating the expression of genes associated with CSC maintenance. TEAD4 contributes to metastasis by modulating the secretion of paracrine factors and promoting heterotypic cellular communication. In this paper, we highlight the central role of TEAD4 in cancer metastasis and chemoresistance and its impact on various aspects of tumor biology. Understanding the mechanistic basis of TEAD4-mediated processes can facilitate the development of targeted therapies and combination approaches to combat cancer metastasis and improve treatment outcomes.
Assuntos
Resistencia a Medicamentos Antineoplásicos , Neoplasias , Humanos , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/patologia , Transição Epitelial-Mesenquimal/fisiologia , Microambiente Tumoral , Fatores de Transcrição de Domínio TEARESUMO
The digital economy is playing a crucial effect in the field of environmental governance. Digital and intelligent management is an essential means to fully realize the "zero-waste city" construction. The present paper investigates the impact of digital economy on China's provincial "zero-waste city" construction. The results indicate that digital economy can contribute to "zero-waste city" construction. The digital economy has a positive nonlinear effect on the construction of "zero-waste city," but the marginal effect is diminishing. The digital economy can facilitate "zero-waste city" construction by improving industrial structure upgrading and green technology innovation. Heterogeneity analysis reveals that digital economy contributes to the construction of "zero-waste city" in the eastern and western regions and high-level environmental regulation regions, while this impact is insignificant in the central region and low-level environmental regulation regions. The digital economy exerts the most significant positive influence on waste resource recycling followed by waste final disposal and then waste reduction at the source. These findings underscore the effect of digital economy in fostering "zero-waste city" construction and promoting sustainable waste management. The present study provides new ideas for the "zero-waste city" construction in emerging developing countries such as China.
Assuntos
Conservação dos Recursos Naturais , Política Ambiental , China , Indústrias , Reciclagem , Desenvolvimento Econômico , CidadesRESUMO
To promote residents' waste separation behavior, waste separation supervision has been a crucial need. This paper aims to explore the supervision mechanism of residents' waste separation behavior using a tripartite evolutionary game model. The evolutionary stability conditions of resident, property service enterprise, and the government were analyzed. The influences of the main parameters on the strategy of three stakeholders were explored through numerical simulation. The results show that the regulatory mechanism of waste separation will reach the optimal stable strategy when the following conditions are satisfied: (1) the penalty for nonclassification is higher than the difference between classification cost and the total benefit of classification; (2) the subsidy to property services enterprise is greater than the total cost of positive participation management. Residents' behaviors are mainly influenced by rewards and punishments. The behavioral strategies of property service companies are more sensitive to subsidies than penalties. In the early stage of mandatory waste separation, it is important to reduce the cost of residents' separation, develop the publics' environmental awareness, and increase the willingness of properties to participate in management. This paper presents a new perspective and theoretical guidelines for the local government and communities to supervise residents' waste separation behaviors in China and other developing countries and offers useful insights into waste separation management for other countries.
Assuntos
Gerenciamento de Resíduos , Gerenciamento de Resíduos/métodos , ChinaRESUMO
OBJECTIVE: To study the changes to surfactant proteins in the serum and bronchoalveolar lavage fluids (BALF) of children with Mycoplasma pneumoniae pneumonia (MPP) and their significance. METHODS: Self-control method was used in the study. Forty-seven MPP children were divided into single lung infected (n=32) and bilateral lung infected groups (n=15) according to lung CT results. Surfactant proteins SP-A, B, C and D were measured using ELISA in the serum and BALF in the two groups. The correlations between SP-A, B, C and D content in the serum and BALF were evaluated by Spearman correlation analysis. RESULTS: SP-A, B, C and D content in BALF from the majorly infected or infected lung were significantly higher than from the opposite lung and serum (P<0.01). SP-A, B and C content in serum was significantly lower than in BALF from the non-infected lung in the single-side infected lung group (P<0.01 or 0.05), but there was no significant difference between serum SP-D content and BALF SP-D content from the non-infected lung. There were no significant differences in SP-A, B, C and D content in serum and BALF from the minorly infected lung in the bilateral lung infected group. Serum SP-D content was positively correlated with BALF SP-D content from the majorly infected lung in the bilateral lung infected group (P<0.01). CONCLUSIONS: Serum SP-D content may serve as a biomarker for evaluating the severity of pulmonary infection in children with community-acquired pneumonia.
Assuntos
Líquido da Lavagem Broncoalveolar/química , Pneumonia por Mycoplasma/metabolismo , Surfactantes Pulmonares/análise , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Surfactantes Pulmonares/sangueRESUMO
The collaborative agglomeration of manufacturing and producer services is an essential tool for the green transformation of China's economic model. This paper explores the impact of industrial collaborative agglomeration on carbon intensity, using the spatial Durbin model (SDM) based on China's provincial panel data from 2012 to 2019. The empirical results indicate that there is an inverted N-shaped relationship between industrial collaborative agglomeration and carbon intensity, with the turning points of 2.5255 and 2.8575. Regional industrial collaborative agglomeration tends to initially reduce carbon intensity, then aggravates to carbon emission, then finally inhibits carbon intensity. There is an obvious heterogeneity in the impact of producer-service subsectors and manufacturing collaborative agglomeration on carbon intensity. When the industrial collaborative agglomeration level exceeds a certain threshold, the clustering of information transmission, software and information technology service, and financial intermediation service have the greatest emission reduction potential. Industrial collaborative agglomeration has obvious spatial spillover effect, and carbon intensity has obvious spatial convergence effect. This paper provides some novelties for research perspectives on carbon intensity reduction and theoretical references for the development and implementation of differentiated industrial collaborative agglomeration policies.
Assuntos
Carbono , Indústrias , Dióxido de Carbono/análise , China , Desenvolvimento Econômico , TecnologiaRESUMO
Facing increasingly serious environmental problems, technological innovation has become the key for industrial enterprises to coordinate energy conservation and emission reduction constraints and achieve steady growth of the industrial economy. Considering the impact of energy consumption and environmental pollution on the technological innovation efficiency of industrial enterprises, this paper incorporates industrial energy consumption, pollution control, and wastewater and exhaust emissions into the technical inefficiency equation. Based on the panel data of industrial enterprises in 30 provinces and autonomous regions in China from 2009 to 2016, the stochastic frontier analysis (SFA) model is used to study the effect of energy consumption and environmental pollution on technological innovation efficiency of industrial enterprises. The research results show that reducing energy consumption and increasing pollution treatment investment both have a significant driving effect on the improvement of industrial enterprises' technological innovation efficiency. Industrial wastewater and exhaust emissions have the opposite effect; unreasonable input mode of pollution control and personnel allocation have hindered the improvement of industrial enterprises' technological innovation efficiency. The average annual trend of technological innovation efficiency in industrial enterprises shows a curve of first rising, then falling, and rising again. The average values of Chongqing, Zhejiang, and Hunan rank in the top three, and the average values of Qinghai, Heilongjiang, and Inner Mongolia rank the bottom three. The average values of other provinces are higher than 0.9, and the difference is small. A suitable incentive mechanism should be established for industrial enterprises to save energy and reduce emissions and strengthen pollution control, improve the training program for environmental protection technical personnel, and provide important support for improving the green competitiveness of industrial enterprises.
Assuntos
Indústrias , Invenções , China , Eficiência , Poluição AmbientalRESUMO
TRIM family proteins are defined as E3 ubiquitin ligases because of their RING-finger domains. The ubiquitin-like protein interferon-stimulated gene 15 (ISG15) encodes a 15-kDa protein, that is implicated in the posttranslational modification of diverse proteins. Both TRIM29 and ISG15 play both pro-tumoral and anti-tumoral functions in cancer cells derived from different histology. In the current study, we demonstrated that correlation expression of TRIM29 and ISG15 in pancreatic ductal adenocarcinomas (PDACs). The current study demonstrated that TRIM29 knockdown destabilized ISG15 protein via promoting its processing by calpain 3 (CAPN3). Importantly, the current study found that TRIM29 knockdown suppressed cancer stem cell-like features of PDACs, which can be rescued by ISG15 independent of its conjugation function. In addition, the current study demonstrated that extracellular free ISG15 played an important role in maintenance of cancer stem cell-like features of PDACs. Thereby, the current study displayed a novel mechanism by which TRIM29 modulates ISG15 stability via CAPN3-mediated processing, and subsequently extracellular ISG15 maintains the cancer stem cell-like features of PDAC via autocrine mode of action.
Assuntos
Carcinoma Ductal Pancreático/patologia , Citocinas/metabolismo , Proteínas de Ligação a DNA/metabolismo , Células-Tronco Neoplásicas/patologia , Neoplasias Pancreáticas/patologia , Fatores de Transcrição/metabolismo , Ubiquitinas/metabolismo , Animais , Comunicação Autócrina , Calpaína/metabolismo , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Feminino , Técnicas de Silenciamento de Genes , Humanos , Camundongos , Proteínas Musculares/metabolismo , Proteólise , Fatores de Transcrição/genética , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVES: Osteosarcoma is one of common malignant tumors worldwide in the metaphysis of teenagers. The role of lncRNAs in Osteosarcoma has become an emerging area of research. MATERIALS AND METHODS: Cell migration and invasion were analyzed in Osteosarcoma cell following knockdown or overexpression by transfection with small interfering RNA (siRNA) or treated with LPS. Western blotting and Real-time RT-PCR methods were used to analyze the effects of LPS on EMT. RESULTS: We discovered that LPS could regulate cell migration and invasion and promote EMT. At the same time, LPS could regulate the expression of TLR4 and HOTAIR. In addition, knockdown of the expression of TLR4 partially reverses the promotion of cell invasion induced by LPS. CONCLUSIONS: Our results indicated that LPS coordinate the Osteosarcoma through TLR4/HOTAIR.
Assuntos
Neoplasias Ósseas/genética , Lipopolissacarídeos/farmacologia , Osteossarcoma/genética , RNA Longo não Codificante/genética , Receptor 4 Toll-Like/genética , Neoplasias Ósseas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Invasividade Neoplásica , Osteossarcoma/metabolismo , Receptor 4 Toll-Like/metabolismo , Regulação para CimaRESUMO
Bcl-2 associated athanogene 3 (BAG3) is an important molecule that maintains oncogenic features of cancer cells via diverse mechanisms. One of the important functions assigned to BAG3 is implicated in selective macroautophagy/autophagy, which attracts much attention recently. However, the mechanism underlying regulation of autophagy by BAG3 has not been well defined. Here, we describe that BAG3 enhances autophagy via promotion of glutamine consumption and glutaminolysis. Glutaminolysis initiates with deamination of glutamine by glutaminase (GLS), by which yields glutamate and ammonia in mitochondria. The current study demonstrates that BAG3 stabilizes GLS via prohibition its interaction with SIRT5, thereby hindering its desuccinylation at Lys158 and Lys164 sites. As an underlying molecular mechanism, we demonstrate that BAG3 interacts with GLS and decreases SIRT5 expression. The current study also demonstrates that occupation by succinyl at Lys158 and Lys164 sites prohibits its Lys48-linked ubiquitination, thereby preventing its subsequent proteasomal degradation. Collectively, the current study demonstrates that BAG3 enhances autophagy via stabilizing GLS and promoting glutaminolysis. For the first time, this study reports that succinylation competes with ubiquitination to regulate proteasomal GLS degradation.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Proteínas Reguladoras de Apoptose/metabolismo , Autofagia/genética , Estabilidade Enzimática/genética , Glutaminase/metabolismo , Glutamina/metabolismo , Neoplasias/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Amônia/metabolismo , Proteínas Reguladoras de Apoptose/genética , Glutaminase/genética , Células Hep G2 , Humanos , Células MCF-7 , Mitocôndrias/metabolismo , Neoplasias/patologia , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Sirtuínas/metabolismo , Transfecção , UbiquitinaçãoRESUMO
BAG3 is a member of the cochaperone BAG family and often highly expressed in various cancers. Recently, evidences show that BAG3 promotes stemness of human cancer cells. IFN-stimulated genes 15 (ISG15) is an ubiquitin-like molecule, which is covalently conjugated with substrates to form ISGylated proteins. Global screening BAG3 interacting partners demonstrated that ISG15 might be a potential binding partner. The current study revealed that BAG3 did not interact with ISG15, but positively regulated ISG15 expression in pancreatic ductal adenocarcinoma cancer (PDAC). It was further found that BAG3 deletion stabilized ISG15 mRNAs, while suppressed its translation via increasing Serine phosphorylation of Ago2 at position 387 (S387). Both BAG3 deletion and ISG15 knockdown suppressed stem cell-like phenotypes of PDAC cells, including clonogenicity, invasiveness and spheroid formation. In addition, ectopic ISG15 expression rescued the suppressive role of BAG3 deletion in cancer stem cell (CSC)-like phenotypes of PDAC cells, and this effect of ISG15 was independent of its ISGylation function. The current study implies that BAG3 and ISG15 may provide a therapeutic advantage for PDAC.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Proteínas Reguladoras de Apoptose , Carcinoma Ductal Pancreático , Citocinas , Deleção de Genes , Proteínas de Neoplasias , Neoplasias Pancreáticas , Biossíntese de Proteínas , Ubiquitinas , Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Idoso , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Carcinoma Ductal Pancreático/patologia , Linhagem Celular Tumoral , Citocinas/biossíntese , Citocinas/genética , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Células-Tronco Neoplásicas , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Ubiquitinas/biossíntese , Ubiquitinas/genéticaRESUMO
Aerobic glycolysis, a phenomenon known historically as the Warburg effect, is one of the hallmarks of cancer cells. In this study, we characterized the role of BAG3 in aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) and its molecular mechanisms. Our data show that aberrant expression of BAG3 significantly contributes to the reprogramming of glucose metabolism in PDAC cells. Mechanistically, BAG3 increased Hexokinase 2 (HK2) expression, the first key enzyme involved in glycolysis, at the posttranscriptional level. BAG3 interacted with HK2 mRNA, and the degree of BAG3 expression altered recruitment of the RNA-binding proteins Roquin and IMP3 to the HK2 mRNA. BAG3 knockdown destabilized HK2 mRNA via promotion of Roquin recruitment, whereas BAG3 overexpression stabilized HK2 mRNA via promotion of IMP3 recruitment. Collectively, our results show that BAG3 promotes reprogramming of glucose metabolism via interaction with HK2 mRNA in PDAC cells, suggesting that BAG3 may be a potential target in the aerobic glycolysis pathway for developing novel anticancer agents.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Adenocarcinoma/genética , Proteínas Reguladoras de Apoptose/genética , Regulação Neoplásica da Expressão Gênica , Hexoquinase/genética , Neoplasias Pancreáticas/genética , Proteínas de Ligação a RNA/genética , Ubiquitina-Proteína Ligases/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Animais , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Proteína 9 Associada à CRISPR , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Proliferação de Células , Repetições Palindrômicas Curtas Agrupadas e Regularmente Espaçadas , Endonucleases/genética , Endonucleases/metabolismo , Fibroblastos/citologia , Fibroblastos/metabolismo , Edição de Genes , Glucose/metabolismo , Glicólise/genética , Hexoquinase/metabolismo , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Transplante de Neoplasias , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Cultura Primária de Células , RNA Guia de Cinetoplastídeos/genética , RNA Guia de Cinetoplastídeos/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Proteínas de Ligação a RNA/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
BACKGROUND: It has been proposed that cyclin G1 (CCNG1) participates in p53-dependent G1-S and G2 checkpoints and might function as an oncogenic protein in the initiation and metastasis of ovarian carcinoma. MicroRNA 23b (miR-23b) is a critical regulatory factor in the progression of many cancer cell types that targets the relevant genes. METHODS: MiR-23b expression in ovarian tissues was quantified by quantitative reverse transcription-PCR. The ovarian cancer cell lines OVCAR3, HO8910-PM, and SKOV3/DDP were transfected with miR-23b, after we assayed the cell phenotype and expression of the relevant molecules. Dual-luciferase reporter assay and a xenograft mouse model were used to examine the expression of miR-23b and its target gene CCNG1. RESULTS: MIR23B mRNA expression was significantly lower in epithelial ovarian carcinoma and borderline tumors than in normal ovarian tissues and benign tumors, and miR-23b expression among ages and pathological subtypes was significantly different. CCNG1 mRNA expression was significantly lower in normal ovarian tissues than in benign tumors, borderline tumors, and ovarian carcinomas, and expression among pathological subtypes was significantly different. MiR-23b overexpression inhibited ovarian cancer cell proliferation, invasion, and migration, and induced apoptosis. Dual-luciferase reporter assay showed that miR-23b bound with the 3' untranslated region of CCNG1. MiR-23b overexpression significantly downregulated CCNG1, urokinase, survivin, Bcl-xL, P70S6K, and matrix metallopeptidase-9 (MMP9) mRNA and protein expression. Furthermore, miR-23b inhibited tumor growth and suppressed CCNG1 expression in vitro. CONCLUSIONS: Our findings show that miR-23b may inhibit ovarian cancer tumorigenesis and progression by downregulating CCNG1 and the expression of the relevant genes. MiR-23b is a potentially novel application for regulating ovarian carcinoma progression.
Assuntos
Ciclina G1/genética , MicroRNAs/genética , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Regiões 3' não Traduzidas , Animais , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação para Baixo , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Transplante de Neoplasias , PrognósticoRESUMO
OBJECTIVE: To study the alterations and relationship of surfactant protein (SP)-A, SP-D and KL-6 in serum and bronchoalveolar lavage fluids (BALF) in children with Mycoplasma pneumoniae pneumonia (MPP). METHOD: Self-control method was used for the study on SP-A, SP-D and KL-6 in serum, infected and non-infected BALFs in 32 MMP children with only one side of MPP. RESULT: The contents of SP-A, SP-D and KL-6 in infected BALF were [mg/L;M (IQR) ]: 243 (90-468) , 187 (43-333) , 148 (47-426) ;104 (37-257) , 56 (25-131) , 35 (12-147) in non-infected BALF; 35 (25-69) , 33 (9-149) and 24 (15-62) in serum. The correlation coefficient of KL-6 between serum and infected BALF were -0.534 and -0.378 (P < 0.05). CONCLUSION: There were significant correlation between the alterations of SP-A, SP-D and KL-6 in serum and lung infection in children with CAP. KL-6 in serum may be more sensitive than SP-A and SP-D.