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1.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 55(10): 789-793, 2020 Oct 09.
Artigo em Chinês | MEDLINE | ID: mdl-33045793

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is one of the most common malignant tumors, which is prone to tumor recurrence and metastasis. At present, surgery combined with radiotherapy and chemotherapy is the conventional modality for HNSCC patients, but for patients who have tumor relapse or metastasis, the treatment outcome is not ideal and the prognosis is pretty poor. Thus, to deepen the understanding of tumor mechanism will be very crucial. Post-translational modification (PTM) refer to covalent binding of small chemical molecular groups on the amino acid side chain of proteins, which is an important way of protein function regulation as well as a research hotspot of epigenetics. In recent years, it has been found that the occurrence of tumor is often accompanied by the abnormality of PTM. The abnormality plays an important role in the development of tumor and can be used as a target of tumor diagnosis and treatment. Many types of protein PTM involve in the development of HNSCC. This paper reviews the relationship between HNSCC and several major protein PTM types, including acetylation, methylation, glycosylation, in order to provide clues for the clinicians in diagnosis and treatment of HNSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Carcinoma de Células Escamosas de Cabeça e Pescoço , Carcinoma de Células Escamosas/genética , Neoplasias de Cabeça e Pescoço/genética , Humanos , Recidiva Local de Neoplasia , Processamento de Proteína Pós-Traducional
2.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 38(5): 550-557, 2020 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-33085241

RESUMO

OBJECTIVE: To investigate the mechanism underlying the regulation of the invasion and metastasis of oral squamous cell carcinoma (OSCC) by long-chain noncoding RNA (lncRNA) PCGEM1 through the transforming growth factor (TGF) ß2/Smad2 signaling pathways. METHODS: A total of 60 OSCC cases were collected. Cancer tissues and normal tissues more than 2 cm away from cancer tissues were also collected. Real-time quantitative polymerase chain reaction (qRT-PCR) was used to detect the expression of miR-148a and lncRNA PCGEM1 in OSCC, adjacent normal tissues, oral mucosa epithelial cells, KB, BcaCD885, SCC-4, CAL27, and SCC-15. The relationship between the expression of lncRNA PCGEM1 and miR-148a and the clinicopathological information of patients was analyzed. The lncRNA PCGEM1-silenced cell line KB-siPCGEM1 and negative control (KB-NC) group were constructed, and KB was used as the blank control group. The effects of lncRNA PCGEM1 on the proliferation, invasion, and migration of KB cells were determined via MTT, Transwell, and scratch assays. The bioinformatics website starBase was used to predict the complementary binding microRNA (miRNA) of lncRNA PCGEM1. Furthermore, the genes that the miRNA could target and bind were predicted in accordance with the website www.microRNA.org. Western blotting analysis was used to detect the expression of TGF ß2/Smad2 signaling pathway proteins. RESULTS: qRT-PCR results showed that the expression level of lncRNA PCGEM1 and miR-148a in OSCC tissues was higher than that in normal tissues (P<0.05). The expression of lncRNA PCGEM1 and miR-148a in the cancer tissues of patients with different TNM grades, lymph node metastasis, and tissue differentiation was statistically significant (P<0.05). Compared with those in the blank control group and the KB-NC group, OD492 nm value was significantly decreased and cell mobility was significantly reduced in the KB-siPCGEM1 group (P<0.05). Bioinformatics predictions showed that lncRNA PCGEM1 could bind to miR-148a in a complementary manner and that miR-148a had a targeted binding site with TGF ß2. qRT-PCR and Western blotting analysis results showed that the expression levels of miR-148a, TGF ß2, and p-Smad2 in the KB-siPCGEM1 group were significantly lower than those in the blank control and KB-NC groups (P<0.05), and no statistically significant difference between the blank control group and the KB-NC group was observed (P>0.05). CONCLUSIONS: LncRNA PCGEM1 is highly expressed in OSCC. The high expression of lncRNA PCGEM1 may enhance the TGF ß2/Smad2 signaling pathway by upregulating miR-148a, thus promoting the development of OSCC.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , RNA Longo não Codificante , Carcinoma de Células Escamosas/genética , Proliferação de Células , Células Epiteliais , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Bucais/genética , RNA Longo não Codificante/genética , Transdução de Sinais , Proteína Smad2 , Fator de Crescimento Transformador beta2
3.
Shanghai Kou Qiang Yi Xue ; 29(3): 267-274, 2020 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-33043343

RESUMO

PURPOSE: To investigate the molecular mechanism of LncRNA NEAT1 regulating proliferation, migration and invasion of tongue squamous cell carcinoma cells by regulating miR-339-5p/ITGA3 axis. METHODS: qRT-PCR and Western blot were used to detect the expression of NEAT1, miR-339-5p, ITGA3 mRNA and ITGA3 protein in 25 cases of human tongue squamous cell carcinoma, its corresponding adjacent tissues, human normal oral mucosal cell line HOK and human tongue squamous cell carcinoma cell lines TSCCA, CAL27, SCC15 and HN13. CAL27 cell lines that inhibited NEAT1 and overexpressed miR-339-5p were constructed, respectively. Cell viability was detected by MTT assay, cell numbers of migration and invasion were detected by Transwell assay, and the expression of Cyclin D1 and MMP-9 proteins were detected by Western blotting. The dual luciferase reporter gene was used to verify the targeting relationship of NEAT1, miR-339-5p and ITGA3, and the regulatory relationship was detected by Western blotting and qRT-PCR. SPSS 17.0 software package was used for statistical analysis of the data. RESULTS: Compared with normal human oral mucosal cell line HOK, the expression of NEAT1 and ITGA3 was up-regulated, while the expression of miR-339-5p was down-regulated in human tongue squamous cell carcinoma cell lines. Inhibition of NEAT1 or over-expression of miR-339-5p significantly inhibited proliferation, migration and invasion of CAL27 cells, and significantly inhibited expression of Cyclin D1 and MMP-9 proteins. Dual luciferase reporter gene assay confirmed that NEAT1 directly interacted with miR-339-5p and suppressed its expression. miR-339-5p negatively regulated ITGA3 expression. Inhibition of NEAT1 reversed the inhibitory effect of the inhibition of miR-339-5p on proliferation, migration and invasion of CAL27 cells. CONCLUSIONS: LncRNA NEAT1 promotes proliferation, migration and invasion of tongue squamous cell carcinoma cells by down-regulating miR-339-5p/ITGA3 axis.


Assuntos
Carcinoma de Células Escamosas , MicroRNAs , RNA Longo não Codificante/fisiologia , Carcinoma de Células Escamosas/genética , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Humanos , Integrina alfa3 , MicroRNAs/genética , RNA Longo não Codificante/genética
4.
Medicine (Baltimore) ; 99(39): e22257, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991423

RESUMO

Cutaneous squamous cell carcinoma (cSCC) is a common skin cancer with an increasing incidence. As a pre-cancerous condition, actinic keratosis (AK) has an up to 20% risk of progression to cSCC. This study aims to define the potential genes that associated with genesis and progression of cSCC, thereby further identify critical biomarkers for the prevention, early diagnosis, and effective treatment of cSCC.Two datasets GSE42677 and GSE45216 were downloaded from the GEO. Microarray data analysis was applied to explore the differentially expressed genes (DEGs) between cSCC samples and AK samples. Then functional enrichment analysis, protein-protein interaction (PPI) network, and drug-gene interaction analysis were performed to screen key genes.A total of 711 DEGs, including 238 upregulated genes and 473 downregulated genes, were screened out. DEGs mainly involved in pathways as extracellular matrix (ECM)-receptor interaction, hematopoietic cell lineage, phosphatidylinositol 3-kinase (PI3K-Akt) signaling pathway, and focal adhesion. Candidate genes, including upregulated genes as JUN, filamin A (FLNA), casein kinase 1 delta (CSNK1D), and histone cluster 1 H3 family member f (HIST1H3F), and downregulated genes as androgen receptor (AR), heat shock protein family H member 1 (HSPH1), tropomyosin 1 (TPM1), pyruvate kinase, muscle (PKM), LIM domain and actin binding 1 (LIMA1), and synaptopodin (SYNPO) were screened out. In drug-gene interaction analysis, 13 genes and 44 drugs were identified.This study demonstrates that genes JUN, FLNA, AR, HSPH1, and CSNK1D have the potential to function as targets for diagnosis and treatment of cSCC.


Assuntos
Carcinoma de Células Escamosas/genética , Análise em Microsséries/normas , Neoplasias Cutâneas/genética , Biomarcadores Tumorais/genética , Bases de Dados Genéticas , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Ceratose Actínica/genética , Mapas de Interação de Proteínas , Melhoria de Qualidade
5.
Zhonghua Kou Qiang Yi Xue Za Zhi ; 55(8): 578-585, 2020 Aug 09.
Artigo em Chinês | MEDLINE | ID: mdl-32842350

RESUMO

Objective: To investigate the effect and molecular mechanism of hsa_circ_0008898 on the cell proliferation, migration, invasion and tumor formation of oral squamous cell carcinoma (OSCC). Methods: Quantitative real-time PCR (qPCR) and Western blotting were used to detect the expression of hsa_circ_0008898, miR-197-5p and ras homolog gene family member A (RHOA) in OSCC tissues, adjacent tissues, OSCC cells and human normal oral keratinocytes (NOK). CAL27 and SCC-25 cells were transfected with si-hsa_circ_0008898#1 (knockdown group 1), si-hsa_circ_0008898#2 (knockdown group 2), hsa_circ_0008898 (circ overexpression group) and blank plasmid (circ blank group), respectively. Then miR-197-5p inhibitor (inhibition group) and blank plasmid (inhibition control group) were transfected into hsa_circ_0008898 knockdown cells (knockdown group 1). CAL27 and SCC-25 cells were transfected with miR-197-5p mimics (miR overexpression group) and blank plasmid (miR blank group), and then transfected hsa_circ_0008898 vector (co-transfection group 1), RHOA vector (co-transfection group 2) and blank plasmid (co-transfection control group) in cells overexpressing miR-197-5p. Cell counting kit 8 (CCK-8), colony formation, Transwell and scratch test were used to detect cell proliferation, cloning ability, cell cycle distribution, cell invasion and migration ability. Ten nude mice were equally divided into two groups, with 5 mice in each group. SCC-25 cells transfected with blank plasmid (control group) and SCC-25 cells transfected with sh-hsa_circ_0008898 (knockout group) were subcutaneously injected into the armpit. The volume and mass of the tumor were measured. Results: The expressions of hsa_circ_0008898 (2.89±0.72) and RHOA (2.62±0.21) in OSCC tissues were significantly higher than those in para-carcinoma tissues (1.00±0.48, 1.00±0.11, respectively), while the expression of miR-197-5p in OSCC tissues (0.46±0.24) was significantly lower than that in para-carcinoma tissues (1.00±0.42) (P<0.05). Compared with NOK, the expression of hsa_circ_0008898 and RHOA in CAL27 and SCC-25 cells increased significantly, while the expression of miR-197-5p decreased (P<0.05). Compared with circ blank group, the cell viability, colony formation, scratch healing rate and invasive cell number of CAL27 and SCC-25 cells in knockdown group 1 and group 2 were significantly decreased, while the proportion of cells in G1 phase was significantly increased (P<0.05). Compared with inhibition control group, the cell viability, colony formation, scratch healing rate and invasive cell number of CAL27 and SCC-25 in inhibition group were significantly increased, while the proportion of cells in G1 phase was significantly decreased in inhibition group (P<0.05). Compared with miR blank group, the cell viability, colony formation, scratch healing rate and invasive cell number of CAL27 and SCC-25 in miR overexpression group were significantly decreased, while the proportion of cells in G1 phase was significantly increased in miR overexpression group (P<0.05). Compared with co-transfection control group, the cell viability, colony formation, migration area and invasive cell number of CAL27 and SCC-25 in co-transfection group2 were significantly increased, while the proportion of cells in G1 phase was significantly decreased in co-transfection group 2 (P<0.05). The volume and mass of transplanted tumor in knockout group ï¼»(660.4±67.8) mm(3 )and (0.60±0.06) g, respectivelyï¼½ were significantly lower than those in control group ï¼»(1 210.4±198.9) mm(3) and (1.00±0.12) g, respectivelyï¼½. Conclusions: Knockdown of hsa_circ_0008898 inhibited OSCC cells proliferation, cloning, migration and invasion and induced cell cycle arrest in vitro by regulating the miR-197-5p/RHOA. Additionally, Knockdown of hsa_circ_0008898 also inhibited tumor formation of OSCC cells in vivo.


Assuntos
Carcinoma de Células Escamosas/genética , MicroRNAs , Neoplasias Bucais/genética , Animais , Linhagem Celular Tumoral , Humanos , Camundongos , Camundongos Nus , RNA Circular
6.
PLoS One ; 15(8): e0238120, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833992

RESUMO

PURPOSE: Conjunctival squamous cell carcinoma (SCC) is primarily treated with surgical resection. SCC has various stages, and local recurrence is common. The purpose of this study was to determine molecular localization of epidermal growth factor receptor (EGFR) and the possibility of EGFR as a biomarker for the management of conjunctival SCC. METHODS: In this retrospective study, we performed immunohistochemistry to evaluate EGFR expression and localization in tumor cells, EGFR mutation-specific expression (E746-A750del and L858R), and human papillomavirus expression in a series of 29 conjunctival SCCs. RESULTS: All 29 tumors in our cohort were EGFR positive (100%). Twenty-one of 29 tumors (72%) showed focal EGFR staining, and seven (28%) showed diffuse EGFR staining. In addition, we calculated the percentages of the two most important mutations in EGFR (exon 19 746-A750del (8/29, 27.5%), exon 21 (L858R mutant (2/29, 6.8%)) in conjunctival SCCs. We observed that the translocation of EGFR from the membrane into the cytoplasm was related to clinical prognosis, as we detected correlations between EGFR cytoplasmic staining and final orbital exenteration and between decreased EGFR membrane staining and progression-free survival. CONCLUSIONS: EGFR is important in the pathology of ocular surface squamous neoplasia including SCC and is a prognostic factor. Increased understanding of EGFR mutations may have important implications for future treatment options.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias da Túnica Conjuntiva/genética , Adenocarcinoma/patologia , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/metabolismo , Estudos de Coortes , Neoplasias da Túnica Conjuntiva/metabolismo , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Neoplasias de Cabeça e Pescoço/genética , Humanos , Imuno-Histoquímica/métodos , Neoplasias Pulmonares/genética , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/genética , Prognóstico , Estudos Retrospectivos
7.
Anticancer Res ; 40(7): 3759-3764, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32620615

RESUMO

BACKGROUND/AIM: Oral squamous cell carcinoma (OSCC) is an aggressive malignancy due to its increased ability for local metastases and distant lymph node metastases. Extensive cytogenetic analyses have detected chromosome instability (CI) patterns in OSCC including gross chromosome numerical alterations, such as polysomy and sporadically monosomy that negatively affect the biological behaviour of the malignancy. Our aim was to investigate the frequency and impact of chromosome 17 (Chr 17) numerical imbalances in OSCC. MATERIALS AND METHODS: Fifty (n=50) formalin-fixed, paraffin-embedded primary OSCCs tissue sections were used. Chromogenic in situ hybridization (CISH) was implemented for detecting Chr 17 centromeric numerical imbalances. Concerning the screening process in CISH slides, a novel real-time reference and calibration grid platform was implemented. RESULTS: Chr 17 multiple copies were observed in 12/50 (24%) of the examined cases. Polysomy was observed in 10/50 (20%) tissue sections, monosomy in 2/50 (4%), whereas the rest of them demonstrated a normal, diploid pattern (38/50-76%). Chr 17 numerical differences were associated with the grade of differentiation of the examined tumors (p=0.001). CONCLUSION: Chr 17 numerical imbalances (polysomy predominantly and monosomy) are observed in sub-groups of OSCCs correlating with a progressive dedifferentiation of malignant tissues. The proposed grid-based platform on CISH slides provides a novel, fast and accurate screening-mapping mechanism for detecting chromosome numerical aberrations.


Assuntos
Carcinoma de Células Escamosas/genética , Cromossomos Humanos Par 17/genética , Neoplasias Bucais/genética , Instabilidade Cromossômica/genética , Aberrações Cromossômicas , Feminino , Humanos , Hibridização in Situ Fluorescente/métodos , Masculino
8.
Gene ; 757: 144936, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-32640301

RESUMO

Oral squamous cell carcinoma (OSCC) accounts for nearly 90 percent of oral cavity malignancies and is one of the most widespread oral cancers in the world. The microRNAs (miRNAs or miRs) have an important role in cellular processes comprising cell cycle, differentiation, and also apoptosis. MiRNAs are also implicated in the progression of cancers, including OSCC, through a variety of signaling pathways. One of the most significant signaling pathways in OSCC is the PI3K / Akt pathway that has been illustrated to be under the tight regulation of miRNAs. Deregulation or activation of the PI3K / Akt pathway due to mutations has been revealed to be implicated in the development of oral cancer. According to studies, more than 47% of HNSCC and around 38% of OSCC samples indicate at least one molecular alteration in this signaling pathway. The potential of miRNAs for their use as therapeutic tools in the diagnosis as well as treatment of numerous diseases have been confirmed. In the current review, we summarize miRNAs and their possible mechanisms as well as their functions in OSCC advancement and progression.


Assuntos
Carcinoma de Células Escamosas/genética , MicroRNAs/genética , Neoplasias Bucais/genética , Animais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/metabolismo , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo
9.
DNA Cell Biol ; 39(10): 1789-1798, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32716650

RESUMO

Head and neck squamous cell carcinoma (HNSCC) is a malignancy with relatively high incidence and poor prognosis. RNA-binding proteins (RBPs) were reported to be dysregulated in multiple cancers and were closely associated with tumor initiation and progression. However, an integrated analysis of the roles of RBPs in HNSCC has not been conducted. In the present study, we obtained transcriptome data and corresponding clinical information of HNSCC patients from The Cancer Genome Atlas database and screened out differentially expressed RBPs between tumor and normal tissues. Subsequently, we utilized a series of bioinformatics analyses to elucidate the potential functions and prognostic value of these RBPs in HNSCC. As a result, a total of 88 aberrantly expressed RBPs were identified, including 63 downregulated and 25 upregulated RBPs. Functional enrichment analysis suggested that the differentially expressed RBPs mainly participated in mRNA metabolic processes, RNA processing, RNA transport, regulation of RNA stability, RNA degradation, and mRNA surveillance pathway. Three RBP genes (NOVA1, EZH2, and RBM24) were determined as prognosis-related hub genes from which EZH2 and NOVA1 were selected to construct a prognostic signature based on LASSO Cox regression algorithm. Further analysis demonstrated that the high-risk patient group stratified by the risk signature has advanced tumor grade and poorer overall survival when compared with low-risk group. Moreover, univariate analysis showed that the risk score, tumor stage, T stage, and N stage were significantly associated with patient overall survival and the multivariate analysis results indicated that the risk score and age were greatly correlated with patient prognosis. Overall, this study provided a comprehensive landscape of RBPs in HNSCC and identified an effective gene signature for predicting the clinical outcomes of HNSCC patient, which may contribute to clinical decision making and individualized cancer treatment.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Neoplasias de Cabeça e Pescoço/genética , Proteínas de Ligação a RNA/genética , Idoso , Biomarcadores Tumorais/metabolismo , Carcinoma de Células Escamosas/patologia , Feminino , Neoplasias de Cabeça e Pescoço/metabolismo , Neoplasias de Cabeça e Pescoço/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas de Ligação a RNA/metabolismo , Análise de Sobrevida
10.
Life Sci ; 256: 118026, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32615187

RESUMO

AIM: We aimed to determine the biological processes and pathways involved in cervical carcinogenesis associated with high-risk human papillomavirus (HPV) infection. MATERIALS AND METHODS: Total RNA was extracted from three formalin-fixed paraffin-embedded (FFPE) samples each of normal cervix, HPV-infected low-grade squamous intraepithelial lesion (LSIL), high-grade SIL (HSIL) and squamous cell carcinoma (SCC). Transcriptomic profiling by microarrays was conducted followed by downstream Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. RESULTS: We examined the difference in GOs enriched for each transition stage from normal cervix to LSIL, HSIL, and SCC, and found 307 genes to be differentially expressed. In the transition from normal cervix to LSIL, the extracellular matrix (ECM) genes were significantly downregulated. The MHC class II genes were significantly upregulated in the LSIL to HSIL transition. In the final transition from HSIL to SCC, the immunoglobulin heavy locus genes were significantly upregulated and the ECM pathway was implicated. CONCLUSION: Deregulation of the immune-related genes including MHC II and immunoglobulin heavy chain genes were involved in the transitions from LSIL to HSIL and SCC, suggesting immune escape from host anti-tumour response. The extracellular matrix plays an important role during the early and late stages of cervical carcinogenesis.


Assuntos
Genes de Cadeia Pesada de Imunoglobulina/genética , Genes MHC da Classe II/genética , Infecções por Papillomavirus/complicações , Lesões Intraepiteliais Escamosas Cervicais/patologia , Neoplasias do Colo do Útero/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/virologia , Regulação para Baixo , Matriz Extracelular/genética , Feminino , Perfilação da Expressão Gênica , Humanos , Estadiamento de Neoplasias , Infecções por Papillomavirus/genética , Lesões Intraepiteliais Escamosas Cervicais/genética , Lesões Intraepiteliais Escamosas Cervicais/virologia , Transcriptoma , Regulação para Cima , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/virologia
11.
DNA Cell Biol ; 39(9): 1583-1594, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32635759

RESUMO

MicroRNAs (miRNAs)-related single-nucleotide polymorphisms (SNPs) have been shown to be implicated in the susceptibility to different types of cancer, including esophageal squamous cell carcinoma (ESCC). Identification of miRNA-related SNPs may provide candidate biomarkers for early diagnosis of ESCC. We performed a genome-wide microarray assay to identify differentially expressed miRNAs, which indicated that the miR-15 family may play an important role in ESCC biology. We then investigated the association of miR-15 family-related SNPs with ESCC. Five miR-15 family-related SNPs were genotyped in 300 patients and 418 controls. Unconditional logistic regression was used to evaluate the relationships of these SNPs with ESCC. Generalized multifactor dimensionality reduction was employed to analyze the SNP-SNP and SNP-smoking interactions. The expression quantitative trait loci (eQTL) databases were queried for in silico functional validation. We found that miR-15b SNP rs1451761T>G was associated with a significantly decreased risk of ESCC and there was a significant SNP-SNP interaction between rs1451761 and rs2740545. SNP-smoking interaction analysis also indicated that the association between rs1451761 and ESCC risk could be changed by smoking status. Additionally, the eQTL analysis revealed that rs1451761 was significantly correlated with structural maintenance of chromosomes 4 and karyopherin subunit alpha 4 mRNA expression. Our results suggest that miR-15b SNP rs1451761 may affect an individual's susceptibility to ESCC, alone and in SNP-SNP and SNP-smoking interaction manners.


Assuntos
Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Carcinoma de Células Escamosas/epidemiologia , Cromossomos Humanos Par 4/genética , Feminino , Humanos , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Locos de Características Quantitativas , Fumar/epidemiologia , alfa Carioferinas/genética , alfa Carioferinas/metabolismo
12.
DNA Cell Biol ; 39(9): 1521-1531, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32721231

RESUMO

Previous studies suggested that alterations in the energy metabolism might be underlying cancer initiation and progression. Polymorphisms of genes involved in energy metabolism regulation, such as peroxisome proliferator-activated receptor gamma coactivator 1α (PPARGC1A), -ß (PPARGC1B), and paraoxonase 1 (PON1), might confer susceptibility to esophageal squamous cell carcinoma (ESCC) and partially explain its pathogenesis. We investigated the effects of several single nucleotide polymorphisms (SNPs) in three metabolic-related genes (e.g., PPARGC1A, PPARGC1B, and PON1) on ESCC susceptibility. In total, 829 patients with sporadic ESCC and 1522 nontumor controls were enrolled in the study. SNPs were genotyped using PCR-ligase detection reaction. Our study revealed that the PPARGC1A rs3736265 G/A SNP significantly increased the risk for ESCC (GA vs. GG: adjusted odds ratio [OR] = 1.25, 95% confidence interval [95% CI] = 1.02-1.54, p = 0.034; GA+AA vs. GG: adjusted OR = 1.25, 95% CI = 1.03-1.52, p = 0.027]. In addition, a stratified analysis revealed that the PPARGC1A rs3736265 SNP was correlated with the development of ESCC in male and nondrinking subgroups. We also confirmed that the PPARGC1B rs17572019 G/A SNP promoted the risk of ESCC in subgroup with high alcohol intake. The PPARGC1A rs8192678 C/T polymorphism decreased the susceptibility of ESCC in men. These findings highlight that polymorphisms in PPARGC1A and PPARGC1B may contribute to ESCC susceptibility. In the future, further well-designed epidemiological studies are needed to confirm our findings.


Assuntos
Arildialquilfosfatase/genética , Carcinoma de Células Escamosas/genética , Neoplasias Esofágicas/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Polimorfismo de Nucleotídeo Único , Proteínas de Ligação a RNA/genética , Idoso , China , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Am J Chin Med ; 48(5): 1203-1220, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32668971

RESUMO

Lymph node migration results in poor prognoses for nasopharyngeal carcinoma (NPC) patients. Tricetin, a flavonoid derivative, regulates tumorigenesis activity through its antiproliferative and antimetastatic properties. However, the molecular mechanism of tricetin affecting the migration and invasion of NPC cells remains poorly understood. In this paper, we examined the antimetastatic properties of tricetin in human NPC cells. Our results demonstrated that tricetin at noncytotoxic concentrations (0-80 3M) noticeably reduced the migration and invasion of NPC cells (HONE-1, NPC-39, and NPC-BM). Moreover, tricetin suppressed the indicative protease, presenilin-1 (PS-1), as indicated by protease array. PS-1 was transcriptionally inhibited via the Akt signaling pathway but not mitogen-activated protein kinase pathways, such as the JNK, p38, and ERK1/2 pathways. In addition to upregulating GSK-3[Formula: see text] phosphorylation through Akt suppression, tricetin may downregulate the activity of PS-1. Overall, our study provides new insight into the role of tricetin-induced molecular regulation in the suppression of NPC metastasis and suggests that tricetin has prospective therapeutic applications for patients with NPC.


Assuntos
Movimento Celular/efeitos dos fármacos , Cromonas/farmacologia , Neoplasias Nasofaríngeas/genética , Presenilina-1/genética , Presenilina-1/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos , Antineoplásicos Fitogênicos/farmacologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Expressão Gênica , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Neoplasias Nasofaríngeas/patologia , Invasividade Neoplásica/genética
14.
J Cancer Res Ther ; 16(3): 517-520, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32719260

RESUMO

Aim of the Study: Both matrix metalloproteinase-2 (MMP-2) and matrix metalloproteinase-9 (MMP-9) is involved in degradation of extracellular matrix and found to stimulate invasion and metastasis in cancer patients. However, studies on the stage-specific expression of MMPs at different stages of larynx carcinoma are still lacking. In the present study, we compare the expression level of MMP-2 and MMP-9 at different stages of laryngeal carcinoma. Material and Methods: Tumor tissues samples were taken from larynx cancer patients by deep biopsy during direct laryngoscopy. Gene expression for MMP-2 and MMP-9 was analyzed using RT-PCR. Results: Significantly high expression of MMP-2 was observed compared to the MMP-9 at stage IV compared to the less advanced stages of the disease. Conclusion: Present study concluded that the MMP-2 expressed with a greater magnitude as compared to the MMP-9 in advance stages of laryngeal carcinoma.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Escamosas/patologia , Regulação Neoplásica da Expressão Gênica , Neoplasias Laríngeas/patologia , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 9 da Matriz/genética , Adulto , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/cirurgia , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/cirurgia , Pessoa de Meia-Idade , Estadiamento de Neoplasias , RNA Mensageiro/genética , Adulto Jovem
15.
Cell Prolif ; 53(8): e12859, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32588946

RESUMO

OBJECTIVES: Bone mesenchymal stem cells (BMSCs) play critical roles in tumour microenvironment. However, molecular mechanisms of how BMSCs to be recruited and effect subsequent tumour progression are poorly understood in oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: The distribution of CXCL8 was detected by immunohistochemical staining in OSCC tissues. The chemotaxis of conditioned media from different epithelial cells to BMSCs was examined by trans-well assay. Real-time quantitative PCR (qPCR) and ELISA were used to detect the expression of related cytokines and chemokine receptors. The migration of BMSCs was observed in BALB/c nude mice. The roles of BMSCs in proliferation, migration and invasion of OSCC were detected by CCK-8, flow cytometry and trans-well assay. Epithelial-mesenchymal transition (EMT)-related markers were analysed by qPCR and Western blot in vitro, and growth was evaluated in BALB/c nude mice using subcutaneously implanted OSCC in nude mouse model in vivo. RESULTS: Using OSCC, we show CXCL8, secreted by OSCC, binds to exclusively CXCR2 in BMSCs to facilitate migration of BMSCs to OSCC. TGF-ß secreted by BMSCs subsequently induces EMT of OSCC to promote their proliferation, migration and infiltration. We also showed that the Ras/Raf/Erk axis plays a critical role in tumour progression. CONCLUSIONS: Our results provide the molecular basis for BMSC recruitment into tumours, and how this process leads to tumour progression and leads us to develop a novel OSCC treatment target.


Assuntos
Carcinoma de Células Escamosas/patologia , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica/genética , Células-Tronco Mesenquimais/citologia , Neoplasias Bucais/genética , Transdução de Sinais , Fator de Crescimento Transformador beta/metabolismo , Animais , Caderinas/metabolismo , Carcinoma de Células Escamosas/genética , Movimento Celular/fisiologia , Proliferação de Células/fisiologia , Interleucina-8/metabolismo , Masculino , Camundongos Nus , Neoplasias Bucais/imunologia , Receptores de Interleucina-8B/metabolismo , Microambiente Tumoral/fisiologia
16.
Life Sci ; 256: 117955, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32534038

RESUMO

AIMS: Cancer associated fibroblasts (CAFs) play a crucial role in lung tumor development, but the underlying mechanism is still not fully understood. MAIN METHODS: SCRIB expression in the CAFs of human lung cancer tissues was examined by immunohistochemistry (IHC). A coculture of mouse Lewis lung cancer cells (LLC) and fibroblasts was used to investigate SCRIB expression in cocultured fibroblasts. Proliferation, scratch wound, and transwell assays were used to examine the proliferation, migration and invasion ability of SCRIB knockdown fibroblasts and their effects on LLC. A 3D-coculture system and co-injection xenograft model were used to examine LLC invasion. RNA sequencing and transwell experiments were used to explore the molecules that may participate in LLC invasion. KEY FINDINGS: Herein, we found that the low expression of SCRIB in CAFs is correlated with advanced tumor stages and poor survival for human lung squamous cell carcinoma. SCRIB expression in fibroblasts is drastically downregulated by LLC cells. SCRIB knockdown fibroblasts not only enhance invasion but also facilitate LLC invasion in a 3D-coculture system and in an in vivo subcutaneous transplantation model. The upregulation of asporin in SCRIB knockdown fibroblasts is involved in LLC invasion in vitro. SIGNIFICANCE: Collectively, the results indicate that fibroblasts with low SCRIB expression promote lung cancer cell invasion, which suggests that the downregulated expression of SCRIB may represent one of the important characteristics of tumor-promoting CAFs in lung squamous cell cancer.


Assuntos
Fibroblastos Associados a Câncer/metabolismo , Regulação Neoplásica da Expressão Gênica , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Proteínas de Membrana/genética , Proteínas Supressoras de Tumor/genética , Animais , Fibroblastos Associados a Câncer/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Regulação para Baixo/genética , Proteínas da Matriz Extracelular/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Masculino , Proteínas de Membrana/metabolismo , Camundongos Endogâmicos C57BL , Modelos Biológicos , Invasividade Neoplásica , Fosfatidilinositol 3-Quinases/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Supressoras de Tumor/metabolismo
17.
Immunol Med ; 43(3): 121-129, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32546118

RESUMO

The roles of interleukin-22 (IL-22) in carcinogenesis have been proposed in various neoplasms. Increased expression of IL-22 has been observed in oral squamous cell carcinoma (OSCC) lesions as well as in other cancers. OSCC is still associated with poor prognosis and a high mortality rate because of its invasiveness and frequent lymph node metastasis. In the present study, we investigated the effects of IL-22 on OSCC cells. The human OSCC cell lines Ca9-22 and SAS were stimulated with IL-22 (1-10 ng/mL), and their migration abilities were examined using a cell scratch assay. A Matrigel invasion assay was performed to evaluate the invasion abilities of OSCC cells. Signal transducer and activator of transcription 3 (STAT3) phosphorylation, matrix metalloproteinase (MMP) and epithelial-mesenchymal transition (EMT)-related genes and proteins were also examined. IL-22 treatment promoted the migration and invasion abilities of OSCC cells without increasing their viability. IL-22 stimulation also induced STAT3 phosphorylation, MMP-9 activity and EMT-related genes and proteins. Our findings suggest that IL-22 has possible roles in the development of OSCC.


Assuntos
Carcinoma de Células Escamosas/patologia , Movimento Celular/efeitos dos fármacos , Interleucinas/efeitos adversos , Interleucinas/fisiologia , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Expressão Gênica/efeitos dos fármacos , Expressão Gênica/genética , Humanos , Metástase Linfática/genética , Metaloproteinase 9 da Matriz/genética , Metaloproteinase 9 da Matriz/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Invasividade Neoplásica/genética , Fosforilação/genética , Fator de Transcrição STAT3/genética , Fator de Transcrição STAT3/metabolismo
18.
Nat Cell Biol ; 22(7): 758-766, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32483388

RESUMO

Cancer-associated fibroblasts (CAFs) perform diverse roles and can modulate therapy responses1. The inflammatory environment within tumours also influences responses to many therapies, including the efficacy of oncolytic viruses2; however, the role of CAFs in this context remains unclear. Furthermore, little is known about the cell signalling triggered by heterotypic cancer cell-fibroblast contacts and about what activates fibroblasts to express inflammatory mediators1,3. Here, we show that direct contact between cancer cells and CAFs triggers the expression of a wide range of inflammatory modulators by fibroblasts. This is initiated following transcytosis of cytoplasm from cancer cells into fibroblasts, leading to the activation of STING and IRF3-mediated expression of interferon-ß1 and other cytokines. Interferon-ß1 then drives interferon-stimulated transcriptional programs in both cancer cells and stromal fibroblasts and ultimately undermines the efficacy of oncolytic viruses, both in vitro and in vivo. Further, targeting IRF3 solely in stromal fibroblasts restores oncolytic herpes simplex virus function.


Assuntos
Fibroblastos Associados a Câncer/imunologia , Instabilidade Genômica , Fator Regulador 3 de Interferon/metabolismo , Proteínas de Membrana/metabolismo , Terapia Viral Oncolítica , Neoplasias Cutâneas/imunologia , Células Estromais/imunologia , Adulto , Animais , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/terapia , Células Cultivadas , Citocinas , Interações Hospedeiro-Patógeno , Humanos , Fator Regulador 3 de Interferon/genética , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Vírus Oncolíticos/genética , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Células Estromais/metabolismo , Células Estromais/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
19.
J Cancer Res Clin Oncol ; 146(7): 1711-1723, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32356177

RESUMO

PURPOSE: As a type of cancer with the highest morbidity and mortality, lung squamous cell carcinoma (LUSC) has a very poor prognosis. Long-non-coding RNA (lncRNA) has recently attracted attentions because it can play the role of competing endogenous RNA (ceRNA) to inhibit microRNA (miRNA) functions. In this study, we aimed to find prognosis-related lncRNAs, miRNAs and mRNAs and construct a prognosis-related ceRNA network. METHODS: The original LUSC RNA-sequencing data and miRNA profiles data were downloaded from the cancer genome atlas (TCGA) database. Differentially expressed lncRNAs, miRNAs and mRNAs were then identified between patients with lymph node metastasis and no lymph node metastasis. Univariate Cox regression analysis was performed to find the survival-associated lncRNAs, miRNAs and mRNAs. Subsequently, prognostic-related ceRNA network was established. By multivariate Cox regression analysis, three lncRNA signatures and three mRNA signatures were developed and used for predicting LUSC patients' survival. RESULTS: A total of 224 lncRNAs, 160 miRNAs, 913 mRNAs were identified between samples with lymph node metastasis and no lymph node metastasis. Univariate Cox regression analysis showed that, among them, 28 lncRNAs, 8 miRNAs, 105 mRNAs were significantly associated with patients' overall survival time. Further pathway and enrichment analysis suggested that these mRNAs were associated with the regulation of transmembrane transport, regulation of blood circulation, plasma lipoprotein particle organization. Then we constructed a survival-related ceRNA network including 9 lncRNAs, 8 miRNAs and 23 mRNAs. Additionally, a multivariate Cox regression analysis demonstrated that three lncRNAs (AL161431.1, LINC02389, APCDD1L.DT) and three mRNAs (KLK6, SLITRK5, CCDC177) had a significant prognostic value. Risk score indicated that lncRNA signature and mRNA signature could independently predict overall survival in LUSC patients. CONCLUSION: The current study provided a better understanding of the ceRNA network in the progression of LUSC and laid a theoretical foundation for LUSC prognosis.


Assuntos
Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/mortalidade , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , MicroRNAs , Interferência de RNA , RNA Longo não Codificante , RNA Mensageiro , Biomarcadores Tumorais , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/patologia , Metástase Linfática , Prognóstico , Curva ROC
20.
J Cancer Res Clin Oncol ; 146(8): 1971-1978, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32447484

RESUMO

PURPOSE: Interleukin-10 (IL-10) is an immunoregulatory cytokine and its cervical and serum concentrations have been associated with a poor prognosis of cervical cancer. The rs1800872 polymorphism (c.-592C>A) in the promotor region of the IL-10 gene affects the production and expression of IL-10 and thus is able to determine the immune response profile in the cervix. Therefore, the aim of this work is to state the association between IL-10 c.-592C>A polymorphism and cervical cancer. METHODS: Genomic DNA was extracted from patient's peripheral blood and tumor biopsy. Socio-demographic, sexual behavior and reproductive characteristics data were collected using a questionnaire. RESULTS: Co-dominant model in logistic binary regression adjusted for confounders, showed that patients presenting with C/A genotype had 2.15 times more chances for developing cervical cancer (OR 2.15; CI95% 1.02-4.56). The dominant model, C/A + A/A, was also independently associated with 2.71 times more chances for cervical cancer development when compared to control patients (OR 2.71; CI95% 1.05-4.47). CONCLUSION: Our study analyses show the association between cervical cancer and IL-10 c.-592C>A polymorphism, demonstrating that the allele A presence was independently associated with higher risks of cervical cancer development.


Assuntos
Interleucina-10/genética , Neoplasias do Colo do Útero/genética , Adenocarcinoma/sangue , Adenocarcinoma/genética , Adenocarcinoma/imunologia , Adulto , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Estudos de Casos e Controles , DNA/sangue , DNA/genética , Feminino , Genótipo , Humanos , Interleucina-10/biossíntese , Interleucina-10/imunologia , Polimorfismo de Nucleotídeo Único , Regiões Promotoras Genéticas , Neoplasias do Colo do Útero/sangue , Neoplasias do Colo do Útero/imunologia
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