RESUMO
Thyroid cancer (TC) is a highly heterogeneous endocrine malignancy with an increased incidence in women than in men. Previous studies regarding the pathogenesis of TC focused on the pathological changes of the tumor cells while ignoring the importance of the mesenchymal cells in tumor microenvironment. However, more recently, the stable environment provided by the interaction of thyroid cancer cells with the peri-tumoral stroma has been widely studied. Studies have shown that components of an individual's immune system are closely related to the occurrence, invasion, and metastasis of TC, which may affect response to treatment and prognosis of the patients. This article presents a comprehensive review of the immune cells, secreted soluble mediators and immune checkpoints in the immune microenvironment, mechanisms that promoting TC cells immune evasion and existing immunotherapy strategies. Besides it provides new strategies for TC prognosis prediction and immunotherapy.
RESUMO
Laryngeal cancer has the second highest incidence of head and neck malignant tumors worldwide. In recent years, studies have shown that human papillomavirus (HPV) infection may be a high-risk factor for laryngeal cancer and closely related to the development and prognosis of laryngeal cancer. The mechanism of the occurrence and development of laryngeal cancer caused by HPV infection needs investigation, as does a rapid and effective HPV detection method for effectively preventing the occurrence of laryngeal cancer and controlling its development. Many studies have explored the relation between HPV infection and laryngeal cancer. Here we review the research progress in investigating HPV infection in terms of DNA, mRNA and protein levels in the occurrence and development of laryngeal cancer and routine HPV detection methods.
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Fascin actin-bundling protein 1 (FSCN1) is an evolutionarily conserved actin-bundling protein that plays a critical role in cell migration, motility, adhesion, and cellular interactions. Although multiple clinical studies have implicated the expression of FSCN1 in laryngeal squamous cell carcinoma (LSCC) progression, the precise mechanism of FSCN1 in the process has not been clearly elucidated. To define FSCN1 function, we characterized FSCN1interacting proteins in two cell lines by immunoprecipitation followed by mass spectrometry (MS). After data filtering, 119 proteins with expression in both the Hep-2 and TU-177 cell samples were identified as FSCN1-interacting partners. With in-depth bioinformatics analysis, we linked FSCN1 to critical cellular processes including cell adhesion, glycolysis/gluconeogenesis, regulation of protein ubiquitination, ribosomal RNA processing, and small molecule metabolism. We discuss the interactions between FSCN1 and some of the newly validated partners. The identification of these potential partners of FSCN1 expands our knowledge of the FSCN1 interactome and provides a valuable resource for understanding the functions of this protein in LSCC progression.
Assuntos
Carcinoma de Células Escamosas/metabolismo , Proteínas de Transporte/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Laríngeas/metabolismo , Espectrometria de Massas/métodos , Proteínas dos Microfilamentos/metabolismo , Proteoma/análise , Carcinoma de Células Escamosas/patologia , Humanos , Neoplasias Laríngeas/patologia , Mapas de Interação de Proteínas , Células Tumorais CultivadasRESUMO
This study intends to investigate the transcriptional regulatory role of miR-145-5p in laryngeal squamous cell carcinoma (LSCC). LSCC cell line TU-177 is transfected with miR-145-5p mimics, generating miR-145-5p-overexpression LSCC cells. Whole transcriptome microarrays are used to investigate the differentially expressed lncRNAs, circRNAs, mRNAs, and miRNAs. The target genes of miRNAs are predicted and performed functional annotation. Additionally, the circRNAs, lncRNAs, and mRNAs that interact with miRNAs are predicted, and then the competing endogenous RNAs (ceRNAs) are predicted. Microarray analysis identifies 26 miRNAs, 248 mRNAs, 1118 lncRNAs, and 382 circRNAs differentially expressed in miR-145-5p overexpressed LSCC cells. Overall, 675 target genes are identified for the differentially expressed miRNAs, which involved in cell adhesion associated gene ontology (GO) terms, and MAPK and FoxO signaling pathways. The up-regulated mRNAs involved in the pathway of ABC transporters, while the down-regulated mRNAs involved in pathway of olfactory transduction. Moreover, 149 ceRNAs are predicted, which are associated with apoptosis, Wnt pathway, and metabolic pathway. Furthermore, qPCR results confirm that miR-145-5p affects expression of lncRNAs, miRNAs, mRNAs, and circRNAs in LSCC cells. Collectively, miR-145-5p may be inhibits LSCC progression via ceRNA-mediated pathways, such as WNT2B-miR-145-5p-NONHSAT127539.2, CASP10-miR-145-5p-NONHSAT127539.2, CASP10-miR-145-5p-circ_0003519, and TPO-miR-145-5p-circ_0003519.
Assuntos
Carcinoma de Células Escamosas/genética , Redes Reguladoras de Genes , Neoplasias Laríngeas/genética , MicroRNAs/metabolismo , Linhagem Celular Tumoral , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , MicroRNAs/genética , Anotação de Sequência Molecular , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
Laryngeal squamous cell carcinoma (LSCC) is the most common head and neck cancer. Astragali radix extracts play crucial roles in the regulation of cancer progression. However, the role of Astragali radix extracts in LSCC and the related mechanisms remains unclear. Here, we evaluated the inhibitory effects of the combined use of Astragali radix total flavonoid (TFA) and cisplatin (CDDP) on an LSCC mouse model by pharmacodynamics. Ultra-high-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) was employed to define the prototype of TFA in vivo. The potential drug targets were identified through the integrative analysis of LSCC microarrays, RNA sequencing data and the main bioactive component of TFA. Furthermore, a protein-protein interaction network, compound-target network and target-pathway network were constructed based on the prototype and potential drug targets to identify the main targets and pathways. Animal experiments showed that TFA has significant synergistic antitumor activity with cisplatin and attenuates the nephrotoxicity caused by CDDP chemotherapy, improving the survival of LSCC-bearing mice. Using UPLC-MS/MS, we identified 8 constituents of TFA in experimental mice serum: formononetin, ononin, calycosin, calycosin-7-O-ß-D-glucoside, 7,2'-dihydroxy-3',4'-dimethoxyisoflavan, 7,2'-dihydroxy-3',4'-dimethoxyisoflavaneglucoside, 3-hydroxy-9,10-dimethoxypterocarpan and 9,10-dimethoxyptercarpan-3-O-ß-d-glucoside. Integrative analysis predicted 19 target genes for TFA constituents, and the target genes were mainly involved in the EGFR-related cancer signaling, metabolism and oxidative stress. Collectively, these findings highlight the role of TFA in the regulation of LSCC and provide potential targets for a high-efficiency and low-toxicity therapeutic strategy of LSCC.