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1.
Cell Prolif ; : e13373, 2022 Dec 14.
Artigo em Inglês | MEDLINE | ID: mdl-36519208

RESUMO

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.

2.
Front Bioeng Biotechnol ; 10: 1025155, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36440435

RESUMO

Orally administered colon-targeted delivery vehicles are of major importance in the treatment of inflammatory bowel disease (IBD). However, it remains a challenge to maintain the integrity of such delivery vehicles during treatment, particularly in the gastric environment, which may cause untimely drug release before reaching the targeted colon. Herein, an oral colon-targeted drug delivery system (OCDDS) based on acetylated konjac glucomannan (AceKGM) has been developed in this work, which accomplishes colonic localization release and targets local inflammatory macrophages. The AceKGM nanoparticle-loading curcumin (Cur) was successfully fabricated by emulsion solvent evaporation techniques. DLS, AFM, and SEM were used in order to evaluate the nanoparticles' diameter as well as their in vitro drug release profile, and reactive oxygen species (ROS) scavenging results showed that the OCDDS considerably retained the activity of Cur treated with simulated gastric fluid (SGF) and controllably released in simulated intestinal fluid (SIF). In addition, the adhesion experiment results indicated that the nanoparticle could accumulate on the colonic macrophages. Evaluations in colitis mice showed that the treatment significantly alleviated the symptoms of colitis by decreasing the local level of myeloperoxidase (MPO) and the disease activity index (DAI) score in mice. In summary, the results of our research demonstrate that Cur-AceKGM nanoparticles exhibit significantly improved therapeutic efficacy compared to orally administered free Cur and can be developed as an effective drug delivery vehicle for IBD treatment.

3.
Oral Dis ; 2022 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-36076350

RESUMO

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.

4.
J Oncol ; 2022: 7574458, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36016581

RESUMO

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.

5.
Int J Biol Macromol ; 218: 335-345, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35870629

RESUMO

Chitosan-based nanogels are effective carriers for drug delivery due to their biocompatibility and biodegradability. However, the chemically cross-linked nanogels usually require complicated procedures or tough conditions. Herein, we report a simple approach to generate chitosan-based nanogels by photo-crosslinking of poor solvent-induced nanoaggregates without requiring any emulsifying agent, catalyst, or external crosslinker. O-nitrobenzyl alcohol-modified carboxymethyl chitosan was synthesized and self-crosslinked into the nanogels in a mixed solution of ethanol and water under 365 nm light irradiation due to UV-induced primary amine and o-nitrobenzyl alcohol cyclization. The nanogels (CMC-NBA NPs) and lactobionic acid-decorated nanogels (LACMC-NBA NPs) displayed a uniform diameter (~200 nm) and excellent stability under physiological conditions. Notably, the nanogels exhibited a high loading content (~28 %) due to π-π stacking and electrostatic interactions between doxorubicin (DOX) and the carriers. These DOX-loaded nanogels showed rapid drug release under slightly acidic conditions. The cell and animal experiments confirmed that LACMC-NBA NPs increased cellular uptake, improved cytotoxicity in tumor cells, and enhanced growth inhibition in vivo than CMC-NBA NPs. Thus, these photo-crosslinked nanogels possess great potential for DOX delivery.


Assuntos
Quitosana , Animais , Quitosana/química , Doxorrubicina/química , Doxorrubicina/farmacologia , Portadores de Fármacos/química , Géis , Concentração de Íons de Hidrogênio , Nanogéis
6.
Cell Prolif ; 55(10): e13293, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35822247

RESUMO

OBJECTIVES: As a result of the current limitation of therapeutic strategies, the repair and regeneration of oviduct injuries required an alternative treatment. We present a novel approach to treat oviduct injuries through a dental pulp stem cells (DPSCs)-based therapy. MATERIALS AND METHODS: In vitro and in vivo models have been established. Immunofluorescence staining, flow cytometry and enzyme-linked immunosorbent assay (ELISA) analysis were used to investigate the features and angiogenic properties of DPSCs, as well as their impact on macrophages, in vitro. For the in vivo experiment with female SD rat model, immunohistochemical staining and ELISA analysis were used to assess the effects of DPSCs on the repair and regeneration of damaged oviducts. RESULTS: The present data showed that intraperitoneal injection of DPSCs reduced the expression of IL-6 and TNF-α to inhibit the immunoreaction in injured sites, as well as increased the expression of VEGF to promote the in situ formation of vessel-like structures, thus the repair and recovery process could be initiated. CONCLUSIONS: We concluded that DPSCs-based therapy could be a novel potential technique for restoring the structure and function of damaged oviduct by enhancing immuno-regulated effect and promoting angiogenic property.


Assuntos
Células-Tronco , Fator A de Crescimento do Endotélio Vascular , Animais , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Polpa Dentária/metabolismo , Feminino , Humanos , Imunomodulação , Interleucina-6/metabolismo , Oviductos/metabolismo , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismo
7.
Front Cell Dev Biol ; 10: 888598, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35663398

RESUMO

Objective: To explore the repair effect of the prepared drug-loaded AM1241 poly(ethylene glycol)-dithiothreitol (PEG-DTT) hydrogel on cranial bone defects in SD rats. Methods: The PEG-DTT hydrogel under borax catalysis was quickly prepared, and the characterization of the material was observed by a scanning electron microscope. The effect of AM1241 on cell activity and bone tissue differentiation was tested. The SD rat model of cranial bone defect was established, and the defect was repaired by injecting the prepared hydrogel into the defect. The defect was divided into four groups, namely, sham group, blank group, PEG-DTT group, and PEG-DTT + AM1241 group. The rats were euthanized, and whole cranial bone was taken out for micro-CT and histological observation. Results: The prepared hydrogel is porous; it is liquid when heated to 80°C and a hydrogel when cooled to 25°C. 5-10 µM AM1241 increased osteoblast activity. A moderate amount of AM1241 can promote osteogenic differentiation. Both the PEG-DTT group and PEG-DTT + AM1241 group showed obvious new bone tissue formation, but the PEG-DTT + AM1241 group had a better effect. In addition, the new bone tissue in the PEG-DTT + AM1241 group was significantly more than that in the other groups. Conclusion: The prepared AM1241-loaded PEG-DTT hydrogel showed a good repair effect on SD rats with cranial bone defects. It can be used as materials for cranial bone repair in SD rats with cranial bone defects, but the repair effect is weaker than that of normal bone. These results provide a theoretical and practical basis for its further clinical application.

8.
J Oncol ; 2022: 7453185, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35586208

RESUMO

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.

9.
Bioengineered ; 13(4): 11012-11025, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35481460

RESUMO

Circular RNAs, which are a novel subclass of noncoding RNAs, are reported to be involved in various biological processes. Aberrant expression of circular RNAs may promote cancer progression. The function of circular GOLPH3 RNA (circGOLPH3) in oral squamous cell carcinoma (OSCC) is unclear. In this study, the circGOLPH3 levels in OSCC cell lines were determined using quantitative real-time polymerase chain reaction (qRT-PCR). Gain-of-function and loss-of-function experiments were performed to evaluate the roles of circGOLPH3 in OSCC. Cell counting kit 8, migration, and invasion assays were performed to determine the functions of circGOLPH3. The mechanism of circGOLPH3 in OSCC was investigated using qRT-PCR, western blotting, luciferase activity, and RNA pull-down analyses. Furthermore, the function of circGOLPH3 in vivo was evaluated. circGOLPH3 derived from GOLPH3 was mainly localized to the cytoplasm and exhibited high stability. The expression of circGOLPH3 was upregulated in OSCC cells. circGOLPH3 promoted the growth of OSCC in vitro and in vivo. Additionally, circGOLPH3 upregulated OSCC cell migration and invasion. Mechanistically, circGOLPH3 functioned as a microRNA sponge and downregulated miR-1299 expression. miR-1299 downregulated the expression of LIF by targeting its 3'-untranslated region. Inhibition of the circGOLPH3/miR-1299/LIF axis suppressed the growth, migration, and invasion of OSCC cells. These findings indicate that the circGOLPH3/miR-1299/LIF axis promotes OSCC cell growth, migration, and invasion and that this axis is a potential therapeutic target for OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , Regiões 3' não Traduzidas , Carcinogênese/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias de Cabeça e Pescoço/genética , Humanos , Proteínas de Membrana/genética , Proteínas de Membrana/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Bucais/metabolismo , RNA Circular/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
10.
J Oral Pathol Med ; 51(5): 474-482, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35377493

RESUMO

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.


Assuntos
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 beta
11.
J Biophotonics ; 15(7): e202200014, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-35324088

RESUMO

Stroke usually causes multiple functional disability. To develop novel rehabilitation strategies, it is quite necessary to improve the understanding of post-stroke brain plasticity. Here, we use functional near-infrared spectroscopy to investigate the prefrontal cortex (PFC) network reorganization in stroke patients with dyskinesias. The PFC hemodynamic signals in the resting state from 16 stroke patients and 10 healthy subjects are collected and analyzed with the graph theory. The PFC networks for both groups show small-world attributes. The stroke patients have larger clustering coefficient and transitivity and smaller global efficiency and small-worldness than healthy subjects. Based on the selected network features, the established support vector machine model classifies the two groups of subjects with an accuracy rate of 88.5%. Besides, the clustering coefficient and local efficiency negatively correlate with patients' motor function. This study suggests that the PFC of stroke patients with dyskinesias undergoes specific network reorganization.


Assuntos
Discinesias , Acidente Vascular Cerebral , Análise por Conglomerados , Humanos , Córtex Pré-Frontal/diagnóstico por imagem , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem
12.
Cancer Sci ; 113(9): 2962-2973, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35289035

RESUMO

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.


Assuntos
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 Pescoço
13.
Bioengineered ; 13(3): 6371-6382, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-35240924

RESUMO

Emerging studies indicate that long non-coding RNAs play important roles in oral squamous cell carcinoma (OSCC). However, the function of the majority of long non-coding RNAs is still unclear. Recently, LINC00472 has been reported to play crucial roles in multiple cancers. However, the role of LINC00472 in oral squamous cell carcinoma (OSCC) is still not clear. This study found that LncRNA LINC00472 was significantly down-regulated in several squamous cell carcinoma cancer tissues and OSCC cell lines. Over-expression of LINC00472 in OSCC cells inhibited OSCC progression and alleviated OSCC immune responses. Additionally, we confirmed that LINC00472 functioned as an hsa-miR-4311 sponge and regulated the expression of GNG7 (guanine nucleotide-binding protein, gamma 7). Also, we found that LINC00472 over-expression could suppress xenograft tumor growth in vivo. Our study provides evidence that LINC00472 plays an essential role in inhibiting oral squamous cell carcinoma progression and affecting immune responses by directly binding to hsa-miR-4311 to regulate the expression of GNG7 positively.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias Bucais , RNA Longo não Codificante , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Subunidades gama da Proteína de Ligação ao GTP , Regulação Neoplásica da Expressão Gênica , Neoplasias de Cabeça e Pescoço/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Bucais/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
14.
J Cell Mol Med ; 26(6): 1842-1852, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34117688

RESUMO

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.


Assuntos
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/genética
15.
J Immunol Res ; 2021: 9250207, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34950739

RESUMO

Increasing evidence indicated that the tumor microenvironment (TME) played a crucial role in cancer initiation and progression. Ubiquitin-conjugating enzyme E2C (UBE2C) was differentially expressed in many cancer types. However, the immunological and prognostic roles of UBE2C were unclear. Differentially expressed genes (DEGs) of 29 cancer types were downloaded from GEPIA2 and 4 cancer types failed to download owing to no DEGs. Furthermore, the gene expression profiles, mutation data, and survival data of 33 cancer types were obtained from UCSC Xena. Clinical stage relevance, tumor mutational burden (TMB), TME relevance analysis, and gene set enrichment analysis (GSEA) of DEGs in 33 cancer types were performed. And DEGs were identified in oral squamous cell carcinoma (OSCC) by biological experiments. Previous studies indicated that UBE2C was related to the prognosis of many cancers. In our study, the higher UBE2C expression level meant a terminal clinical stage in 8 cancer types and the expression level of UBE2C was related to TMB in 20 cancer types. In addition, both immune relevance analysis and GSEA showed that UBE2C might participate in immune response in many cancers. Furthermore, the UBE2C mRNA level and protein level were all identified as upregulated in OSCC cell lines and tissues. UBE2C was differentially expressed in many cancer types and related to the pathogenesis and TME of many cancers, which might be a potential diagnostic and therapeutic biomarker.


Assuntos
Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Neoplasias/etiologia , Microambiente Tumoral , Enzimas de Conjugação de Ubiquitina/genética , Adulto , Idoso , Biologia Computacional/métodos , Gerenciamento Clínico , Suscetibilidade a Doenças , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estadiamento de Neoplasias , Neoplasias/diagnóstico , Neoplasias/mortalidade , Neoplasias/terapia , Prognóstico , Modelos de Riscos Proporcionais , Mapeamento de Interação de Proteínas , Transcriptoma , Microambiente Tumoral/genética , Microambiente Tumoral/imunologia , Enzimas de Conjugação de Ubiquitina/metabolismo
16.
Bioengineered ; 12(2): 9585-9597, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34738503

RESUMO

Oral squamous cell carcinoma (OSCC) is one of the most common cancer types of head and neck cancer, accounting for 95% of all cases. However, the mechanisms underlying the pathogenesis of OSCC remain unclear. Circular RNA (CircRNA) has been extensively studied in the past decades and is a promising direction for the development of OSCC therapeutic targets. In this study, we aimed to investigate the role of circMTO1 in OSCC progression. First, we validated the characterization and expression of circMTO1 in OSCC. It was found that circMTO1 was upregulated in OSCC tumor tissues and cells. Subsequently, we conducted biological experiments. It was found that circMTO1 knockdown inhibited OSCC cell proliferation, migration, and invasion. Furthermore, we conducted a series of experiments to elucidate the underlying mechanisms. A novel circMTO1/miR-320a/ATRX axis was identified. Our results suggest that circMTO1 modulates ATRX expression to accelerate OSCC progression by sponging miR-320a. Moreover, we found that circMTO1 expression in OSCC was transcriptionally regulated by Zinc Finger Protein 460 (ZNF460). Our study showed a novel ZNF460/circMTO1/miR-320a/ATRX signaling in OSCC development.


Assuntos
Proteínas de Ligação a DNA/biossíntese , Neoplasias de Cabeça e Pescoço/metabolismo , MicroRNAs/metabolismo , Proteínas de Neoplasias/metabolismo , RNA Circular/metabolismo , RNA Mitocondrial/metabolismo , RNA Neoplásico/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Fatores de Transcrição/biossíntese , Proteína Nuclear Ligada ao X/metabolismo , Linhagem Celular Tumoral , Proteínas de Ligação a DNA/genética , Neoplasias de Cabeça e Pescoço/genética , Humanos , MicroRNAs/genética , Proteínas de Neoplasias/genética , RNA Circular/genética , RNA Mitocondrial/genética , RNA Neoplásico/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Fatores de Transcrição/genética , Proteína Nuclear Ligada ao X/genética
17.
Oral Dis ; 2021 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-34739163

RESUMO

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.

18.
J Cell Mol Med ; 25(23): 10857-10868, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34729919

RESUMO

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.


Assuntos
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/imunologia
19.
J Immunol Res ; 2021: 5524231, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34414241

RESUMO

lncRNAs are related to the progression of various diseases, including oral squamous cell carcinoma (OSCC), which is a common squamous cell carcinoma of the head and neck. Tumor-associated macrophages and tumor cells are significant components of tumor microenvironment. M2 polarization of tumor-associated macrophages is a crucial actor in tumor malignancy and metastasis. In this study, we studied the molecular mechanism of lncRNA DCST1-AS1 in OSCC. Here, we reported that DCST1-AS1 was significantly increased in OSCC cells. We found that loss of DCST1-AS1 obviously inhibited the proliferation, migration, and invasion of OSCC cells and xenograft tumor growth. Meanwhile, silencing of DCST1-AS1 also repressed the percentage of macrophages expressing M2 markers CD206 and CD11b. DCST1-AS1 shRNA enhanced the percentage of macrophages expressing M1 markers CD80 and CD11c. Then, we observed that loss of DCST1-AS1 suppressed OSCC progression via inactivating NF-κB signaling. As well established, NF-κB signaling exerts critical roles in tumor progression, and our study proved that DCST1-AS1 could regulate NF-κB signaling. We proved that blocking the NF-κB pathway using antagonists greatly downregulated OSCC progression and M2 macrophage polarization induced by the overexpression of DCST1-AS1. To sum up, we reported that DCST1-AS1 plays an important role in modulating OSCC tumorigenicity and M2 macrophage polarization through regulating the NF-κB pathway.


Assuntos
Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/metabolismo , Neoplasias Bucais/etiologia , Neoplasias Bucais/metabolismo , NF-kappa B/metabolismo , RNA Longo não Codificante/genética , Transdução de Sinais , Macrófagos Associados a Tumor/metabolismo , Animais , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Modelos Animais de Doenças , Inativação Gênica , Humanos , Ativação de Macrófagos/genética , Ativação de Macrófagos/imunologia , Camundongos , Neoplasias Bucais/patologia , Macrófagos Associados a Tumor/imunologia
20.
J Immunol Res ; 2021: 1830790, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34355042

RESUMO

LINC01355 has been demonstrated to be dysregulated in several cancers. However, the exact molecular function of LINC01355 in the pathogenesis of OSCC remains unstudied. Here, we reported the effect of LINC01355 in OSCC and investigated the mechanisms. Firstly, we found that the results indicated LINC01355 was increased in OSCC cells. Knockdown of LINC01355 repressed OSCC cell proliferation, migration, and invasion. Recently, immunotherapy is a significant method for the treatment of cancers, in which CD8+ T cells exhibit a significant role. The influence of LINC01355 on the antitumor activity of CD8+ T cells was also focused in this study. As shown, the silence of LINC01355 could repress OSCC tumor growth via inducing CD8+ T cell immune responses. In addition, we found that downregulation of LINC01355 significantly restrained CD8+ T cell apoptosis, induced CD8+ T cell percentage, and enhanced the cytolysis activity when cocultured with OSCC cells. It has been reported that the Notch pathway represses CD8+ T cell activity in cancer patients. In our present study, we displayed that lack of LINC01355 suppressed OSCC malignant behaviors and enhanced the antitumor activity of CD8+ T cells via inactivating Notch signaling. We showed that decreased LINC01355 significantly restrained the Notch signal via a decrease of Notch-1, JAG-1, and HES-1. Repression of Notch1 reversed the effect of LINC01355 in OSCC cells. In conclusion, it was implied that LINC01355 might induce the development of OSCC via modulating the Notch signal pathway, which could provide a candidate therapeutic target for OSCC.


Assuntos
Carcinoma de Células Escamosas/etiologia , Carcinoma de Células Escamosas/metabolismo , Linfócitos do Interstício Tumoral/metabolismo , Neoplasias Bucais/etiologia , Neoplasias Bucais/metabolismo , RNA Longo não Codificante/genética , Receptores Notch/metabolismo , Linfócitos T Citotóxicos/metabolismo , Animais , Apoptose/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Regulação Neoplásica da Expressão Gênica , Inativação Gênica , Humanos , Ativação Linfocitária/imunologia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/patologia , Camundongos , Neoplasias Bucais/patologia , Interferência de RNA , Transdução de Sinais , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
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