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The connection between head and neck squamous cell carcinoma (HNSC) and M2 tumour-associated macrophages is not yet fully understood. We gathered gene expression profiles and clinical data from HNSC patients in the TCGA database. Using Consensus Clustering, we categorized these patients into M2 macrophage-related clusters. We developed a M2 macrophage-related signature (MRS) through statistical analyses. Additionally, we assessed gene expression in HNSC cells using single-cell sequencing data (GSE139324). We identified three distinct M2 macrophage-related clusters in HNSC, each with different prognostic outcomes and immune characteristics. Patients with different MRS profiles exhibited variations in immune infiltration, genetic mutations and prognosis. FCGR2A may play a role in creating an immunosuppressive tumour microenvironment and could potentially serve as a therapeutic target for HNSC. Our study demonstrated that M2 macrophage-related genes significantly impact the development and progression of HNSC. The M2 macrophage-related model offered a more comprehensive assessment of HNSC patient prognosis, genetic mutations and immune features. FCGR2A was implicated in immunosuppressive microenvironments and may hold promise for the development of novel immunotherapeutic strategies for HNSC.
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Regulação Neoplásica da Expressão Gênica , Macrófagos , RNA-Seq , Análise de Célula Única , Carcinoma de Células Escamosas de Cabeça e Pescoço , Microambiente Tumoral , Humanos , Análise de Célula Única/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologia , Macrófagos/metabolismo , Macrófagos/imunologia , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Prognóstico , RNA-Seq/métodos , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/imunologia , Neoplasias de Cabeça e Pescoço/patologia , Receptores de IgG/genética , Receptores de IgG/metabolismo , Perfilação da Expressão Gênica , Mutação , Transcriptoma/genética , Masculino , Feminino , Análise da Expressão Gênica de Célula ÚnicaRESUMO
Periodontitis (PD) is a multifactorial inflammatory disease associated with periodontopathic bacteria. Lysine-specific demethylase 1 (LSD1), a type of histone demethylase, has been implicated in the modulation of the inflammatory response process in oral diseases by binding to miRNA targets. This study investigates the molecular mechanisms by which miRNA binds to LSD1 and its subsequent effect on osteogenic differentiation. First, human periodontal ligament stem cells (hPDLSCs) were isolated, cultured, and characterized. These cells were then subjected to lipopolysaccharide (LPS) treatment to induce inflammation, after which osteogenic differentiation was initiated. qPCR and western blot were employed to monitor changes in LSD1 expression. Subsequently, LSD1 was silenced in hPDLSCs to evaluate its impact on osteogenic differentiation. Through bioinformatics and dual luciferase reporter assay, miR-708-3p was predicted and confirmed as a target miRNA of LSD1. Subsequently, miR-708-3p expression was assessed, and its role in hPDLSCs in PD was evaluated through overexpression. Using chromatin immunoprecipitation (ChIP) and western blot assay, we explored the potential regulation of osterix (OSX) transcription by miR-708-3p and LSD1 via di-methylated H3K4 (H3K4me2). Finally, we investigated the role of OSX in hPDLSCs. Following LPS treatment of hPDLSCs, the expression of LSD1 increased, but this trend was reversed upon the induction of osteogenic differentiation. Silencing LSD1 strengthened the osteogenic differentiation of hPDLSCs. miR-708-3p was found to directly bind to and negatively regulate LSD1, leading to the repression of OSX transcription through demethylation of H3K4me2. Moreover, overexpression of miR-708-3p was found to promote hPDLSCs osteogenic differentiation in inflammatory microenvironment. However, the protective effect was partially attenuated by reduced expression of OSX. Our findings indicate that miR-708-3p targetedly regulates LSD1 to enhance OSX transcription via H3K4me2 methylation, ultimately promoting hPDLSCs osteogenic differentiation.
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Cisplatin (CDDP) chemoresistance is one of the predominant factors in oral squamous cell carcinoma (OSCC) treatment failure. Uncovering the mechanisms underlying CDDP resistance is of great importance in OSCC therapy. Circular RNAs (circRNAs) are a newly discovered class of noncoding RNAs, which are reported to participate in the progression of various diseases, including cancer. However, the function of circRNAs in CDDP resistance in OSCC remains unclear. Quantitative reverse transcription PCR was used to search for different circRNAs between OSCC cell lines and CDDP-resistant cell lines. The results showed that circ-ILF2 expression was higher in CDDP-resistant OSCC cell lines. The stability of circ-ILF2 was also confirmed using RNase R and actinomycin D assays. Functional experiments, including cytotoxicity, apoptosis and growth rate assays, showed that upregulation of circ-ILF2 contributes to CDDP resistance. Luciferase reporter-gene, RNA pull-down and quantitative real-time PCR (RT-qPCR) assays showed that circ-ILF2 functions as a microRNA sponge for miR-1252. Luciferase reporter assays, RNA pull-down, RT-qPCR and Western blotting showed that miR-1252 directly targeted and regulated the expression of KLF8. Circ-ILF2 plays an important role in CDDP resistance in OSCC. Circ-ILF2 exerts its function through the miR-1252/KLF8 pathway. In addition, tumour-associated macrophages (TAM) play important roles in cancer progressions, our results showed that circ-ILF2 in OSCC cells induced the M2 polarization of macrophages which provided new thoughts on immunotherapy. Our results suggest that circ-ILF2 may represent a potential therapeutic target in CDDP-resistant OSCC.
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Cisplatino , Resistencia a Medicamentos Antineoplásicos , RNA Circular , Carcinoma de Células Escamosas de Cabeça e Pescoço , RNA Circular/genética , RNA Circular/metabolismo , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Fatores de Transcrição Kruppel-Like/genética , Fatores de Transcrição Kruppel-Like/metabolismo , Macrófagos/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/fisiopatologia , Polaridade Celular/genética , HumanosRESUMO
Oral squamous cell carcinoma (OSCC) is a type of tumour found in the cavity that is characterized by differentiation and metastasis to the lymph nodes. Although diagnosis strategy and clinical treatment have recently improved, the outcomes for OSCC patients remain unsatisfactory. This study verified the characteristics of circPUM1 in OSCC cells, subsequently generating dysregulated circPUM1 cell models, showing that circPUM1 promoted chemoresistance and natural killer (NK) cell toxicity. Furthermore, the transcription factor SP2 regulated the expression of circPUM1 in OSCC cells, circPUM1 acted as a molecular sponge for miR-770-5p. Moreover, Nucleosome Assembly Protein 1 Like 1 (NAP1L1) is a downstream target for miR-770-5p and essential for circPUM1-mediated cisplatin resistance and NK cell cytotoxicity in OSCC cells. The network composed of SP2, circPUM1, miR-770-5p and NAP1L1 in OSCC appears to be a promising avenue for the development of novel targets for diagnosing or treating OSCC.
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BACKGROUND: Lung cancer is a highly prevalent malignancy and has the highest mortality rate among all tumors due to lymph node metastasis. Bone marrow and umbilical cord-derived mesenchymal stem cells (MSCs) have demonstrated tumor-suppressive effects on lung cancer. This study investigated the effects of DPSC lysate on proliferation, apoptosis, migration and invasion of cancer cells were studied in vivo and in vitro. METHODS: The proliferation, apoptosis, and migration/metastasis were evaluated by cell counting kit-8 assay, Annexin-V and propidium iodide staining, and the transwell assay, respectively. The expression levels of apoptosis-, cell cycle-, migration-, and adhesion-related mRNA and proteins were measured by qRT-PCR and western blot. The level and mRNA expression of tumor markers carcino embryonic antigen (CEA), neuron-specific enolase (NSE), and squamous cell carcinoma (SCC) were measured by Enzyme-linked immunosorbent assay (ELISA) and qRT-PCR. Finally, a tumor-bearing mouse model was constructed to observe the tumor-suppressive effect of DPSC lysate after intraperitoneal injection. RESULTS: DPSC lysate decreased the viability of A549 cells and induced apoptosis in lung cancer cells. Western blot confirmed that levels of Caspase-3, Bax, and Bad were increased, and Bcl-2 protein levels were decreased in A549 cells treated with DPSC lysate. In addition, DPSC lysate inhibited the migration and invasion of A549 cells; downregulated key genes of the cell cycle, migration, and adhesion; and significantly suppressed tumor markers. Xenograft results showed that DPSC lysate inhibited tumor growth and reduced tumor weight. CONCLUSIONS: DPSC lysate inhibited proliferation, invasion, and metastasis; promoted apoptosis in lung cancer cells; and suppressed tumor growth- potentially providing a cell-based alternative therapy for lung cancer treatment.
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Neoplasias Pulmonares , Células-Tronco Mesenquimais , Humanos , Camundongos , Animais , Neoplasias Pulmonares/patologia , Polpa Dentária/metabolismo , Polpa Dentária/patologia , Proliferação de Células , Células-Tronco Mesenquimais/metabolismo , RNA Mensageiro/farmacologia , Biomarcadores Tumorais , Apoptose , Movimento Celular , Linhagem Celular TumoralRESUMO
OBJECTIVE: Periodontitis is a chronic inflammation of periodontal tissues. This study is expected to assess the effect of LSD1 on the osteogenic differentiation of hPDLSCs in periodontitis. METHODS: hPDLSCs were separated, cultivated, and identified, and then treated by LPS to induce inflammatory microenvironment and subjected to osteogenic differentiation. Subsequently, LSD1 expression was determined, and then silenced to assess its effect on hPDLSCs. Next, the binding relation between LSD1 and miR-590-3p was analyzed. miR-590-3p expression was detected and then overexpressed to evaluate its role in hPDLSCs in periodontitis. Afterward, the relation between LSD1 and OSX was analyzed. H3K4me2 level and OSX transcription were measured, and the role of H3K4me2 was determined. Additionally, the role of OSX in hPDLSCs was verified. RESULTS: LSD1 was poorly expressed after osteogenic differentiation of hPDLSCs while it was rescued upon LPS induction. The osteogenic differentiation of hPDLSC in periodontitis was strengthened upon LSD1 downregulation. Besides, miR-590-3p targeted LSD1 transcription, and LSD1 inhibited OSX transcription via H3K4me2 demethylation. miR-590-3p overexpression improved osteogenic differentiation of hPDLSCs in periodontitis. But this improvement was annulled by OSX inhibition. CONCLUSION: miR-590-3p targeted LSD1 transcription and upregulated H3K4me2 methylation to promote OSX transcription, thereby encouraging osteogenic differentiation of hPDLSCs in periodontitis.
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MicroRNAs , Periodontite , Humanos , Diferenciação Celular , Células Cultivadas , Histona Desmetilases/genética , Histona Desmetilases/metabolismo , Lipopolissacarídeos/farmacologia , MicroRNAs/genética , MicroRNAs/metabolismo , Osteogênese/genética , Ligamento Periodontal , Periodontite/genética , Periodontite/metabolismo , Células-TroncoRESUMO
Oral squamous cell carcinoma (OSCC) is a pathological type of oral cancer, which accounts for over 90% of oral cancers. It has been widely shown that circRNA is involved in the regulation of multiple malignant oral diseases including OSCC. However, the mechanism underlying how circRNA regulates OSCC is still not clearly elucidated. In this article, we report circFOXO3 promotes tumor growth and invasion of OSCC by targeting miR-214 which specifically degrades the lysine demethylase 2A (KDM2A). CircRNA sequencing was conducted in OSCC tumor and tumor-side tissues, and the expression of circFOXO3 is found to be markedly increased in tumor tissues. CircFOXO3 is also highly expressed in several OSCC cell lines compared with human oral keratinocytes. Transwell assay and colony formation showed that knockdown of circFOXO3 prevents the invasion and proliferation of oral cancer cells. Via bioinformatic research, miR-214 was found to be the target of circFOXO3 and correlate well with circFOXO3 both in vitro and in vivo. KDM2A was then validated by database analysis and luciferase assay to be the direct target of miR-214. KDM2A helps to promote tumor invasiveness and proliferation of OSCC. Collectively, our results proved that circFOXO3 sponges miR-214 to up-regulate the expression of KDM2A, thus promotes tumor progression in OSCC.
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Carcinoma de Células Escamosas , Proteínas F-Box , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Proteínas F-Box/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Humanos , Histona Desmetilases com o Domínio Jumonji/genética , Histona Desmetilases com o Domínio Jumonji/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Bucais/patologia , RNA Circular/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genéticaRESUMO
The high prevalence of oral squamous cell carcinoma (OSCC) in South Asia is associated with habitual areca nut chewing. Arecoline, a primary active carcinogen within areca nut extract, is known to promote OSCC pathological development. Dysregulation of N6-methyladenosine (m6A) modification has begun to emerge as a significant contributor to cancer development and progression. However, the biological effects and molecular mechanisms of m6A modification in arecoline-promoted OSCC malignance remain elusive. We reveal that chronic arecoline exposure substantially induces upregulation of fat mass and obesity-associated protein (FTO), MYC, and programmed cell death-ligand 1 (PD-L1) in OSCC cells. Moreover, upregulation of PD-L1 is observed in OSCC cell lines and tissues and is associated with areca nut chewing in OSCC patients. We also demonstrate that arecoline-induced FTO promotes the stability and expression levels of PD-L1 transcripts through mediating m6A modification and MYC activity, respectively. PD-L1 upregulation confers superior cell proliferation, migration, and resistance to T-cell killing to OSCC cells. Blockage of PD-L1 by administration of anti-PD-L1 antibody shrinks tumor size and improves mouse survival by elevating T-cell-mediated tumor cell killing. Therefore, targeting PD-L1 might be a potential therapeutic strategy for treating PD-L1-positive OSCC patients, especially those with habitual areca nut chewing.
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Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Animais , Apoptose , Areca/efeitos adversos , Areca/metabolismo , Arecolina/farmacologia , Carcinoma de Células Escamosas/patologia , Imunidade , Ligantes , Camundongos , Neoplasias Bucais/patologia , Obesidade/complicações , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
BACKGROUND: Oral submucosal fibrosis (OSF) is a precancerous condition that closely related to the habit of chewing betel nut. The OSF patients of 3%-19% may develop cancer, and this probability is increasing year by year. Epigenetics modifications have been reported as part of the pathogenesis of OSF. However, in OSF field, the role and mechanism of arecoline-induced activation of transforming growth factor ß (TGF-ß) signaling on N6-methyladenosine (m6A) modification remain unclear. In this study, we investigated the effect and mechanism of arecoline on m6A modification. METHODS: MeRIP-Seq and RNA-seq were performed in arecoline-stimulated cells. Quantitative polymerase chain reaction and western blot were performed to detect the expression of m6A writers and erasers. CCK-8 and flow cytometry analyses were performed to measure the cell viability and apoptosis. RESULTS: m6A level was increased in OSF tissues compared to normal tissues; arecoline promoted the m6A methyltransferase Mettl3 and Mettl14 through TGF-ß. MeRIP-seq and RNA-seq analyses found that MYC was the target gene of Mettl14. In addition, Mettl14 silence reversed the effects of arecoline on cell proliferation and apoptosis in Hacat cells. CONCLUSION: TGF-ß-METTL14-m6A-MYC axis was crucially implicated in arecoline-mediated OSF and may be an effective therapeutic strategy for OSF treatment.
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Arecolina , Fibrose Oral Submucosa , Adenosina/análogos & derivados , Adenosina/metabolismo , Arecolina/farmacologia , Humanos , Metiltransferases/genética , Fibrose Oral Submucosa/induzido quimicamente , Fibrose Oral Submucosa/genética , Fator de Crescimento Transformador betaRESUMO
OBJECTIVE: Periodontitis is characterized by alveolar bone injury and absorption, with high incidence and poor treatment effect. Proliferation, migration, differentiation and apoptosis of osteoblasts are identified as key factors during the regeneration of alveolar bone tissue processes. Periodontal ligament stem cells (PDLSCs) have been proved to be a possible candidate for the treatment of periodontitis due to its multiple advantages, such as increasing the regenerative capacity of bone tissue. However, the effect of exosomes derived from PDLSCs (PDLSC-Exo) on osteoblasts remains to be further studied. METHODS AND MATERIALS: In this work, cell proliferation, migration, osteogenic differentiation, and H2 O2 -induced apoptosis were detected after cells were exposed to PDLSC-Exo by CCK-8, scratch wound assay, alizarin red S and alkaline phosphatase staining, real-time PCR, flow cytometry, tunel assay, and so on. Moreover, the activation of PI3K/AKT and MEK/ERK signaling pathways was evaluated by western blotting. RESULTS: We found that PDLSC-Exo are capable of promoting hFOB1.19 cell proliferation, migration and osteogenic differentiation, inhibiting H2 O2 -induced apoptosis, and activating the PI3K/AKT and MEK/ERK signaling pathways. CONCLUSION: These results suggest that PDLSC-Exo may be a promising therapeutic for osteoblastic damage.
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Immunotherapy has been identified a promising treatment of cancers, including Oral squamous cell carcinoma (OSCC). CRNDE is highly overexpressed in various cancers. Many lncRNAs have been reported in CD8 T lymphocytes. Little is investigated about their effects in the functions of CD8 + T cells in OSCC. Currently, the influence of lncRNA CRNDE on the function of CD8 + T cells in OSCC progression was investigated. Here, CRNDE was obviously elevated and negatively correlated with IFN-γ production in tumour-infiltrating CD8 + T cells isolated from OSCC patients. CRNDE can exhibit a crucial role in activating CD8 + T-cell exhaustion. Mechanistically, CRNDE specifically sponged miR-545-5p to induce T-cell immunoglobulin and mucin domain-3 (TIM-3), thus contributing to CD8 + T-cell exhaustion. The function of miR-545-5p on T-cell function remains poorly known. TIM-3 is a significant immune checkpoint, and it inhibits cancer immunity. TIM-3 can demonstrate an important role in CD8 + T-cell exhaustion. In summary, loss of CRNDE could induce miR-545-5p and inhibit TIM3 expression, thus significantly activated the anti-tumour effect of CD8 + T cells.
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Linfócitos T CD8-Positivos/imunologia , MicroRNAs/imunologia , Neoplasias Bucais/imunologia , RNA Longo não Codificante/imunologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/imunologia , Apoptose/imunologia , Carcinoma Hepatocelular/imunologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Regulação Neoplásica da Expressão Gênica/imunologia , Receptor Celular 2 do Vírus da Hepatite A , Humanos , Neoplasias Hepáticas/imunologiaRESUMO
Circular RNAs (circRNAs) have been widely reported to participate in progression of various cancers, including oral cancer. Previous study showed circ_0001461 was aberrantly expressed in oral squamous cell carcinoma (OSCC), while its role in tumorigenesis of OSCC remains largely unclear. In this study, we confirmed that circ_0001461 was highly expressed in OSCC cell lines and tumor tissues. Knocking down of circ_0001461 suppressed cell proliferation, migration and invasion in vitro, and repress xenograft tumor growth in vivo. Mechanistically, we found circ_0001461 regulates OSCC cell proliferation, migration and invasion through sponging miR-145. Furthermore, circ_0001461 promotes the resistance of TNF-α-induced apoptosis of OSCC cells by modulating miR-145/TLR4/NF-κB pathway. In general, our study demonstrated a novel regulatory mechanism that circ_0001461/miR-145/TLR4/NF-κB axis modulates oral squamous cell carcinoma progression.
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Carcinoma de Células Escamosas/genética , MicroRNAs/genética , Neoplasias Bucais/genética , NF-kappa B/genética , RNA Circular/genética , Receptor 4 Toll-Like/genética , Carcinoma de Células Escamosas/patologia , Proliferação de Células , Progressão da Doença , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/patologiaRESUMO
Dysregulation of long non-coding RNAs (lncRNAs) has been implicated in many cancer developments. Previous studies showed that lncRNA LINC00941 was aberrantly expressed in oral squamous cell carcinoma (OSCC). However, its role in OSCC development remains elusive. In this study, we demonstrated that in OSCC cells, EP300 activates LINC00941 transcription through up-regulating its promoter H3K27ac modification. Up-regulated LINC00941 in turn activates CAPRIN2 expression by looping to CAPRIN2 promoter. Functional assays suggest that both LINC00941 and CAPRIN2 play pivotal roles in promoting OSCC cell proliferation and colony formation. In vivo assay further confirmed the role of LINC00941 in promoting OSCC cell tumour formation. Lastly, we showed that the role of LINC00941 and CAPRIN2 in OSCC progression was mediated through activating the canonical WNT/ß-catenin signaling pathway. Thus, LINC00941/CAPRIN2/ WNT/ß-catenin signaling pathway provides new therapeutic targets for OSCC treatment.
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Carcinoma de Células Escamosas/patologia , Neoplasias Bucais/patologia , Proteínas de Neoplasias/fisiologia , RNA Longo não Codificante/metabolismo , RNA Neoplásico/fisiologia , Proteínas de Ligação a RNA/fisiologia , Via de Sinalização Wnt/fisiologia , Animais , Sistemas CRISPR-Cas , Carcinoma de Células Escamosas/genética , Divisão Celular , Células Cultivadas , DNA de Neoplasias/genética , DNA de Neoplasias/ultraestrutura , Progressão da Doença , Proteína p300 Associada a E1A/fisiologia , Regulação Neoplásica da Expressão Gênica , Genes Reporter , Código das Histonas , Queratinócitos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Bucais/genética , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Transplante de Neoplasias , Regiões Promotoras Genéticas/genética , RNA Guia de Cinetoplastídeos/administração & dosagem , RNA Guia de Cinetoplastídeos/genética , RNA Longo não Codificante/genética , RNA Neoplásico/biossíntese , RNA Neoplásico/genética , Proteínas de Ligação a RNA/biossíntese , Proteínas de Ligação a RNA/genética , Proteínas Recombinantes/metabolismo , Ensaio Tumoral de Célula-Tronco , Regulação para Cima , Via de Sinalização Wnt/genéticaRESUMO
Circular RNAs (circRNAs) represent a newly discovered class of endogenous non-coding RNAs which are widely expressed and play important roles in disease progression. However, the function of circRNAs in oral squamous cell carcinoma (OSCC) still remains largely unknown. In this research, we found that circ_SEPT9 was highly expressed in OSCC cell lines and tumour tissues. Results showed that circ_SEPT9 promoted OSCC proliferation and tumour growth. And, circ_SEPT9 also enhanced the migration and invasion of OSCC cells. Mechanically, we found that circ_SEPT9 acted as a sponge for miR-1225 to rescue PKN2 expression in OSCC cells. Inhibition of circ_SEPT9/miR-1225/PKN2 pathway could effectively block the proliferation and metastasis of OSCC cells. Our study provides strong evidence that circ_SEPT9/miR-1225/PKN2 axis is a promising target for OSCC treatment.
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Carcinoma de Células Escamosas/metabolismo , MicroRNAs/metabolismo , Neoplasias Bucais/metabolismo , Proteína Quinase C/metabolismo , RNA Circular/metabolismo , Septinas/metabolismo , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Proteínas do Citoesqueleto/metabolismo , Progressão da Doença , Humanos , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Metástase Neoplásica , Transdução de Sinais , Carcinoma de Células Escamosas de Cabeça e PescoçoRESUMO
OBJECTIVE: This study aimed to develop a pro-angiogenic hydrogel with in situ gelation ability for alveolar bone defects repair. METHODOLOGY: Silk fibroin was chemically modified by Glycidyl Methacrylate (GMA), which was evaluated by proton nuclear magnetic resonance (1H-NMR). Then, the photo-crosslinking ability of the modified silk fibroin was assessed. Scratch and transwell-based migration assays were conducted to investigate the effect of the photo-crosslinked silk fibroin hydrogel on the migration of human umbilical vein endothelial cells (HUVECs). In vitro angiogenesis was conducted to examine whether the photo-crosslinked silk fibroin hydrogel would affect the tube formation ability of HUVECs. Finally, subcutaneous implantation experiments were conducted to further examine the pro-angiogenic ability of the photo-crosslinked silk fibroin hydrogel, in which the CD31 and α-smooth muscle actin (α-SMA) were stained to assess neovascularization. The tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) were also stained to evaluate inflammatory responses after implantation. RESULTS: GMA successfully modified the silk fibroin, which we verified by our 1H-NMR and in vitro photo-crosslinking experiment. Scratch and transwell-based migration assays proved that the photo-crosslinked silk fibroin hydrogel promoted HUVEC migration. The hydrogel also enhanced the tube formation of HUVECs in similar rates to Matrigel®. After subcutaneous implantation in rats for one week, the hydrogel enhanced neovascularization without triggering inflammatory responses. CONCLUSION: This study found that photo-crosslinked silk fibroin hydrogel showed pro-angiogenic and inflammation inhibitory abilities. Its photo-crosslinking ability makes it suitable for matching irregular alveolar bone defects. Thus, the photo-crosslinkable silk fibroin-derived hydrogel is a potential candidate for constructing scaffolds for alveolar bone regeneration.
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Fibroínas , Hidrogéis , Humanos , Animais , Ratos , Regeneração Óssea , Células Endoteliais da Veia Umbilical HumanaRESUMO
Introduction: Curcumin has broad application prospects in the prevention and treatment of periodontal diseases. Periodontal ligament stem cell-derived extracellular vesicles (PDLSC-EV) can effectively promote periodontal tissue regeneration and possess good drug delivery capability. Superior pharmacological effects can be exerted using PDLSC-EV as a curcumin carrier. Methods: In the present study, we constructed curcumin-primed PDLSCs-derived extracellular vesicles (Cur-PDLSC-EV) from cell culture supernatants of curcumin-pretreated PDLSCs by ultracentrifugation and investigated their effects on the proliferation, migration, and osteogenic ability of PDLSCs and the corresponding downstream molecular pathways. Results: Both Cur-PDLSC-EV and PDLSC-EV promoted osteoblast proliferation and migration. Compared with PDLSC-EV, Cur-PDLSC-EV possessed a more potent pro-osteogenic ability. Moreover, the improved osteogenesis of Cur-PDLSC-EV was related to the activation of the Wnt/ß-catenin signaling pathway. Conclusion: This study suggests that Cur-PDLSC-EV can promote osteogenic differentiation by activating Wnt/ß-catenin, providing reference bases for the treatment of periodontal diseases.
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The Epstein-Barr virus (EBV) is involved in the carcinogenesis of gastric cancer (GC) upon infection of normal cell and induces a highly variable composition of the tumour microenvironment (TME). However, systematic bioinformatics analysis of key genes associated with EBV regulation of immune infiltration is still lacking. In the present study, the TCGA and GEO databases were recruited to analyse the association between EBV infection and the profile of immune infiltration in GC. The weighted gene co-expression analysis (WGCNA) was applied to shed light on the key gene modules associated with EBV-associated immune infiltration in GC. 204 GC tissues were used to analysed the expression of key hub genes by using the immunohistochemical method. Real-time PCR was used to evaluate the association between the expression of EBV latent/lytic genes and key immune infiltration genes. Our results suggested that EBV infection changed the TME of GC mainly regulates the TIICs. The top three hub genes of blue (GBP1, IRF1, and LAP3) and brown (BIN2, ITGAL, and LILRB1) modules as representative genes were associated with EBV infection and GC immune infiltration. Furthermore, EBV-encoded LMP1 expression is account for the overexpression of GBP1 and IRF1. EBV infection significantly changes the TME of GC, and the activation of key immune genes was more dependent on the invasiveness of the whole EBV virion instead of single EBV latent/lytic gene expression.
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Carcinoma , Infecções por Vírus Epstein-Barr , Neoplasias Gástricas , Humanos , Herpesvirus Humano 4/genética , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/genética , Neoplasias Gástricas/patologia , Microambiente TumoralRESUMO
Oral squamous cell carcinoma (OSCC) is one of the most lethal cancers worldwide. The high morbidity and mortality of OSCC are a great burden to global health-care systems. Therefore it is important to understand the underlying molecular mechanisms of OSCC initiation and progression. This study aimed to investigate the role of circMAT2B in OSCC progression and its molecular mechanisms. First, the expression and circularization of circMAT2B in OSCC cells were verified. Subsequently, knockdown of circMAT2B was shown to inhibit OSCC cell proliferation, migration, invasion, and the Warburg effect. Bioinformatics prediction, RNA-pull down, and luciferase reporter gene assays led to the identification of a novel TEAD1/circMAT2B/miR-942-5p/HSPD1 axis in OSCC progression. In conclusion, the novel TEAD1/circMAT2B/miR-942-5p/HSPD1 axis is a potential target for OSCC.
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Objectives: Many studies have shown that dysregulation of metabolism contributes to oncogenesis. However, the exact roles of metabolism-related genes (MRGs) in oral squamous cell carcinoma (OSCC) remain unclear. Thus, we aimed to identify a prognostic signature related to MRGs in OSCC. Methods: The gene sequencing data of OSCC samples and the MRG set were downloaded from The Cancer Genome Atlas (TCGA) and the Molecular Signatures Database (MSigDB). The Wilcoxon rank-sum test was used to identify differentially expressed MRGs. Then, a prognostic signature was established by multivariate Cox regression analysis. Finally, prognosis-related MRGs were selected and further validated in OSCC tissues and cell lines. Results: A prognostic signature that included 8 MRGs was constructed. Multiple survival analysis revealed that only HPRT1 might be an independent biomarker and indicator of poor overall survival in OSCC patients. The expression of HPRT1 was then found to be upregulated in OSCC tissues and cell lines, and suppression of HPRT1 gene expression by siRNA inhibited the proliferation, migration, and invasion of OSCC cells in vitro. Conclusions: MRGs play an important role in the development of OSCC. Furthermore, HPRT1 might be an independent biomarker of OSCC and enhance OSCC proliferation, migration, and invasion in vitro; these results emphasize the potential utility of HPRT1 in OSCC therapy.