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BACKGROUND: RING Finger Protein 115 (RNF115), a notable E3 ligase, is known to modulate tumorigenesis and metastasis. In our investigation, we endeavor to unravel the putative function and inherent mechanism through which RNF115 influences the evolution of thyroid carcinoma (THCA). METHODS: We analyzed RNF115 expression in THCA using the Cancer Genome Atlas (TCGA) database. The influence of RNF115 on the progression of THCA was evaluated using both in vitro and in vivo experimental approaches. The protein regulated by RNF115 was identified through bioinformatics analysis, and its biological significance was further explored. RESULTS: In both THCA tissues and cells, RNF115 showed elevated expression levels. Enhanced expression of RNF115 fostered cell proliferation, tumor growth, and the exacerbation of epithelial-mesenchymal transition (EMT) in THCA, while also promoting tumor lung metastasis. Bioinformatics analysis identified cyclin-dependent kinase 10 (CDK10) as a downstream target of RNF115, which was found to be ubiquitinated and degraded by RNF115 in THCA cells. Functionally, overexpression of CDK10 was found to counteract the promotion of malignant phenotype in THCA induced by RNF115. From a mechanistic perspective, RNF115 activated the Raf-1 pathway and enhanced cancer cell cycle progression by degrading CDK10 in THCA cells. CONCLUSION: RNF115 triggers cell proliferation, EMT, and tumor metastasis by ubiquitinating and degrading CDK10. The regulation of the Raf-1 pathway and cell cycle progression in THCA may be profoundly influenced by this process.
Assuntos
Neoplasias Pulmonares , Neoplasias da Glândula Tireoide , Ubiquitina-Proteína Ligases , Humanos , Carcinogênese/genética , Transformação Celular Neoplásica , Quinases Ciclina-Dependentes , Neoplasias da Glândula Tireoide/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
Structural health and construction security are important problems in civil engineering. Regular infrastructure inspection and monitoring methods are mostly performed manually. Early automatic structural health monitoring techniques were mostly based on contact sensors, which usually are difficult to maintain in complex infrastructure environments. Therefore, non-contact infrastructure inspection and monitoring techniques received increasing interest in recent years, and they are widely used in all aspects of infrastructure life, owing to their convenience and non-destructive properties. This paper provides an overview of vision-based inspection and vision-laser-based monitoring techniques and applications. The inspection part includes image-processing algorithms, object detection, and semantic segmentation. In particular, infrastructure monitoring involves not only visual technologies but also different fusion methods of vision and lasers. Furthermore, the most important challenges for future automatic non-contact inspections and monitoring are discussed and the paper correspondingly concludes with state-of-the-art algorithms and applications to resolve these challenges.
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Algoritmos , Lasers , Processamento de Imagem Assistida por ComputadorRESUMO
Kallikrein-associated peptidase 11 (KLK11) has emerged as a key tumor-associated protein that is implicated in a wide spectrum of tumor types. However, the detailed involvement of KLK11 in laryngeal squamous cell carcinoma (LSCC) has not been well studied. The aims of our work were to evaluate whether KLK11 plays a role in LSCC. We found that both the mRNA and protein expression of KLK11 were significantly lower in LSCC tissues than in normal tissues. Low expression of KLK11 was also observed in LSCC cell lines, and the up-regulation of KLK11 caused a significant inhibitory effect on the proliferation, colony formation and invasion of LSCC cells. On the contrary, the knockdown of KLK11 markedly accelerated the proliferative and invasive abilities of LSCC cells. Molecular mechanism research revealed that KLK11 overexpression decreased the phosphorylation of glycogen synthase kinase-3ß (GSK-3ß) and down-regulated the expression of active ß-catenin, leading to the inactivation of Wnt/ß-catenin signaling in LSCC cells. Furthermore, GSK-3ß inhibition markedly abrogated the KLK11-mediated suppressive effect on Wnt/ß-catenin signaling. Notably, the reactivation of Wnt/ß-catenin partially reversed KLK11-mediated tumor-inhibition effect in LSCC. In addition, the xenograft tumor assay demonstrated that the up-regulation of KLK11 retarded tumor formation and the growth of LSCC cells in vivo. Taken together, the findings of our work demonstrate that KLK11 exerts a tumor-inhibition role in LSCC by down-regulating Wnt/ß-catenin signaling. Our work highlights a pivotal role of KLK11 in LSCC progression and suggests it as an attractive anticancer target for LSCC treatment.
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Neoplasias de Cabeça e Pescoço/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina Endopeptidases/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Via de Sinalização Wnt , beta Catenina/metabolismo , Animais , Neoplasias de Cabeça e Pescoço/genética , Neoplasias de Cabeça e Pescoço/patologia , Xenoenxertos , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/patologiaRESUMO
Long non-coding RNA (lncRNA) AGAP2-AS1 acts as an oncogene in several types of cancers. However, the role and mechanism of AGAP2-AS1 in papillary thyroid carcinoma (PTC) remain unclear. Thus, in this study, we aimed to explore the role of AGAP2-AS1 in PTC. Our results showed that AGAP2-AS1 was significantly upregulated in PTC tissues. Knockdown of AGAP2-AS1 inhibited the proliferation, migration and invasion of PTC cells. In vivo experiment showed that AGAP2-AS1 knockdown inhibited the tumorigenesis of PTC. MiR-628-5p was found to act as a target miRNA of AGAP2-AS1 in PTC. The expression level of miR-628-5p in PTC tissues was negatively associated with that of AGAP2-AS1. Inhibition of miR-628-5p attenuated the effects of AGAP2-AS1 knockdown on PTC. Moreover, miR-628-5p directly bound to the 3'UTR of KLF12 and inhibited the expression of KLF12. Knockdown of KLF12 enhanced the inhibitory effects of miR-628-5p on PTC cell proliferation and metastasis. In conclusion, these findings indicated that AGAP2-AS1 exerted an oncogenic role in PTC progression and metastasis. The effects of AGAP2-AS1 might be mediated by the regulation of miR-628-5p/KLF12 axis.
Assuntos
MicroRNAs/metabolismo , RNA Longo não Codificante/genética , Câncer Papilífero da Tireoide/genética , Neoplasias da Glândula Tireoide/genética , Animais , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Fatores de Transcrição Kruppel-Like/metabolismo , Camundongos , Transdução de Sinais , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologiaRESUMO
Background: Thyroid cancer is the most common endocrine malignancy and the fastest growing cancer worldwide. Thyroid cancer has the largest genetic component of all cancers. Previous genome-wide association studies indicated that genetic polymorphism in PCNXL2 is related to thyroid cancer susceptibility in European populations. This study aims to determine the influence of PCNXL2 polymorphisms on thyroid cancer risk in Chinese individuals. Methods: This case-control study identified four polymorphisms in PCNXL2 among 510 thyroid cancer cases and 509 healthy controls. The associations of PCNXL2 polymorphisms with thyroid cancer susceptibility were detected by calculating odds ratios. Multifactor dimensionality reduction was performed to detect the impact of SNP (single nucleotide polymorphism)-SNP interactions on the risk of thyroid cancer. Results: The study showed that rs10910660 in PCNXL2 was related to thyroid cancer susceptibility. Rs12129938 played a protective role in thyroid cancer susceptibility. Stratification analysis indicated that rs10910660 increased thyroid cancer risk at age >45 years. Rs12129938 enhanced susceptibility to thyroid cancer at age >45 years, while this SNP decreased thyroid cancer risk at age ≤45 years. Rs4649295 was associated with lower susceptibility to thyroid cancer at age ≤45 years. An association was observed between rs6424270 and rs12129938 with decreased susceptibility to thyroid cancer in women. Rs10910660 was related to thyroid cancer risk in men. The combination of rs6424270, rs10910660, rs12129938 and rs4649295 was the best model to predict thyroid cancer. Conclusion: This study suggests that PCNXL2 polymorphisms are risk factors for thyroid cancer in the Chinese population.
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Predisposição Genética para Doença , Neoplasias da Glândula Tireoide/genética , Adulto , Alelos , Povo Asiático/genética , Estudos de Casos e Controles , China/epidemiologia , Feminino , Estudo de Associação Genômica Ampla , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Fatores de Proteção , Fatores de Risco , Glândula Tireoide/patologia , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologiaRESUMO
Matrine, a natural product extracted from the root of Sophora flavescens Ait, was the main chemical ingredient of compounds of Kushen injection, which has been widely used for its remarkable anticancer effects for years. The underlying mechanisms for Matrine regulations of human breast cancer stem cells (BrCSCs) are barely known. LIN28, a well-characterized suppressor of Let-7 microRNA biogenesis, playing vital roles in regulations of stem cells' renewal and tumorigenesis. Here we show that the compounds of Kushen injection derived Matrine could suppress the BrCSCs differentiation and self-renewal through downregulating the expression of Lin28A, resulting in the inactivation of Wnt pathway through a Let-7b-dependent way. In opposite to Matrine, Cisplatin treatment increases the ability of tumorsphere formation and the expression of BrCSCs markers, which was partially blocked by either Let-7b overexpression or CCND1 inhibition. Furthermore, Matrine sensitized BrCSCs to cisplatin's suppression of cancer expansion in vitro and in vivo. Our study uncovers the role of the LIN28A/Let-7 in BrCSCs renewal, and more importantly, elucidated a novel mechanism by which Matrine induces breast cancer involution.
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Alcaloides/farmacologia , Neoplasias da Mama/tratamento farmacológico , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Pulmonares/tratamento farmacológico , MicroRNAs/genética , Células-Tronco Neoplásicas/efeitos dos fármacos , Quinolizinas/farmacologia , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Proliferação de Células , Autorrenovação Celular , Feminino , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/secundário , Camundongos , Camundongos SCID , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto , MatrinasRESUMO
BACKGROUND: Parathyroid protection and central neck dissection (CND) are basic points of thyroid cancer surgery and draw persistent concern. We aimed to evaluate the value of carbon nanoparticles (CNs) for parathyroid gland protection and CND in thyroid surgery for thyroid cancer patients. METHODS: A total of 386 consecutive thyroid cancer patients were enrolled in the retrospective study. Three hundred thirty-four patients using CNs intraoperatively were included in the CN group, and 52 patients without using CNs or any other helping agent were included in the control group. Intact parathyroid hormone (iPTH) was examined. Medical records and histopathologic reports were reviewed. Histopathologic examination was performed. RESULTS: There were no statistical significances in demographic and basic surgical information, preoperative iPTH, and serum calcium between the two groups (P > 0.05). In the CN group, the thyroid tissue and central neck lymph nodes were stained black by CNs, while the parathyroid glands were not. Histopathological examination showed that the carbon nanoparticles might accumulated in the subcapsular sinus of lymph nodes compared with the none-stained samples. The staining with CNs did not impact the histopathological examination. There were no significant differences in postoperative hypocalcemia and hypoPT at day 1, 1 month, and half year after surgery between the two groups, respectively. There was a big decline of iPTH level after surgery, whereas the perioperative decreasing amplitude of PTH was not statistically different between the CNs and control group (57.2 ± 28.6 vs 55.7 ± 27.8, P = 0.710). There were 43 patients occurring incidental parathyroidectomy in the CN group (43/334, 12.9%) and 7 patients in the control group (7/52, 13.5%), without significant difference (P = 0.907). There was no significant difference in the number of lymph nodes identified by pathology per patient between the CNs and control group regardless of unilateral and bilateral CND. CONCLUSIONS: Carbon nanoparticles help highlight parathyroid glands and lymph nodes in thyroidectomy, but generate no significant benefit for parathyroid glands protection and lymph node dissection. The value of carbon nanoparticles in thyroid cancer surgery should not be exaggerated and needs further evaluation.
Assuntos
Cuidados Intraoperatórios/métodos , Esvaziamento Cervical/efeitos adversos , Coloração e Rotulagem/métodos , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adulto , Carbono/administração & dosagem , Corantes/administração & dosagem , Estudos de Viabilidade , Feminino , Humanos , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/prevenção & controle , Linfonodos/cirurgia , Masculino , Pessoa de Meia-Idade , Nanopartículas/administração & dosagem , Esvaziamento Cervical/métodos , Glândulas Paratireoides/lesões , Prognóstico , Estudos Retrospectivos , Tireoidectomia/efeitos adversosRESUMO
BACKGROUND: To evaluate the efficacy of a sensitive, real-time tool for identification and protection for parathyroid glands during thyroidectomy. METHODS: Near-infrared (NIR) auto-fluorescence was measured intraoperatively from 20 patients undergoing thyroidectomy. Spectra were measured from suspicious parathyroid glands and surrounding neck tissues during the operation with a NIR fluorescence system. Fast frozen sections were performed on the suspicious parathyroid glands. Accuracy was evaluated by comparison with histology and NIR identification. Data were attracted for Fisher's linear discriminant analysis. RESULTS: The auto-fluorescence intensity of parathyroid was significantly higher than that of thyroid, fat and lymph node. The peak intensity of auto-fluorescence from parathyroid was 5.55 times of that from thyroid at the corresponding wave number. Of the 20 patients, the parathyroid was accurately detected and identified in 19 patients by NIR system, compared with their histologic results. One suspicious parathyroid did not exhibit typical spectra, and was proved to be fat tissue by histology. The NIR auto-fluorescence method had a 100% sensitivity of parathyroid glands identification and a high accuracy of 95%. The positive predictive value was 95%. The parathyroid gland have specific auto-fluorescence spectrum and can be separated from the other three samples through the Fisher's linear discriminant analysis. CONCLUSIONS: NIR auto-fluorescence spectroscopy can accurately identify normal parathyroid gland during thyroidectomy. The Fisher's linear discriminant analysis demonstrated the specificity of the NIR auto-fluorescence of parathyroid tissue and its efficacy in parathyroid discrimination.
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Glândulas Paratireoides/diagnóstico por imagem , Espectrometria de Fluorescência/métodos , Espectroscopia de Luz Próxima ao Infravermelho/métodos , Cirurgia Assistida por Computador/métodos , Glândula Tireoide/cirurgia , Neoplasias da Glândula Tireoide/cirurgia , Tireoidectomia/métodos , Adulto , Idoso , Análise Discriminante , Feminino , Humanos , Período Intraoperatório , Masculino , Pessoa de Meia-Idade , Curva ROC , Neoplasias da Glândula Tireoide/diagnósticoRESUMO
To determine the most suitable strategy in treating patients with invasive breast cancer from Northwest China. Lower recurrence score (RS) correlated with lower recurrence ratio. Patients having a medium-high 21-gene RS who received adjuvant therapy presented lower recurrence risk. Younger patients having RS results (⩾31) tended to accept adjuvant therapy more often, however, those having intermediate RS results were inclined to wait and did not receive chemotherapy. These results suggested that RS-based precision medicine will allow individualized diagnosis and treatment, resulting in better outcomes and preserved medical resources.
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Biomarcadores Tumorais/genética , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Perfilação da Expressão Gênica/métodos , Quimioterapia Adjuvante , China , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Medicina de Precisão , Prognóstico , Análise de Sobrevida , Resultado do TratamentoRESUMO
The ability of the classic tumour-suppressive let-7 family to inhibit carcinogenesis, tumour progression, recurrence and pluripotency of cancer stem cells has generated significant interest in the field of cancer research. Through suppressing and degrading downstream-targeted mRNAs, let-7 affected most aspects of cell biology. It is perplexing how let-7 affects oncogenesis, as the large influx of new miRNAs and other kinds of non-coding RNAs are continuously defined. In this review, we delineate the complex functions of let-7 and discuss the future direction of let-7 research.
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Carcinogênese/genética , MicroRNAs/metabolismo , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Carcinogênese/patologia , Exossomos/metabolismo , Humanos , MicroRNAs/genética , Modelos Biológicos , Neoplasias/genética , Neoplasias/patologia , Neoplasias/terapiaRESUMO
Let-7 miRNAs act as tumour suppressors by directly binding to the 3'UTRs of downstream gene products. The regulatory role of let-7 in downstream gene expression has gained much interest in the cancer research community, as it controls multiple biological functions and determines cell fates. For example, one target of the let-7 family is cyclin D1, which promotes G0/S cell cycle progression and oncogenesis, was correlated with endoribonuclease DICER1, another target of let-7. Down-regulated let-7 has been identified in many types of tumours, suggesting a feedback loop may exist between let-7 and cyclin D1. A potential player in the proposed feedback relationship is Dicer, a central regulator of miRNA expression through sequence-specific silencing. We first identified that DICER1 is the key downstream gene for cyclin D1-induced let-7 expression. In addition, we found that let-7 miRNAs expression decreased because of the p53-induced cell death response, with deregulated cyclin D1. Our results also showed that cyclin D1 is required for Nutlin-3 and TAX-induced let-7 expression in cancer repression and the cell death response. For the first time, we provide evidence that let-7 and cyclin D1 form a feedback loop in regulating therapy response of cancer cells and cancer stem cells, and importantly, that alteration of let-7 expression, mainly caused by cyclin D1, is a sensitive indicator for better chemotherapies response.
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Ciclina D1/genética , RNA Helicases DEAD-box/genética , MicroRNAs/genética , Ribonuclease III/genética , Proteína Supressora de Tumor p53/genética , Regiões 3' não Traduzidas/genética , Apoptose/genética , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Ciclo Celular/genética , Linhagem Celular Tumoral , Sobrevivência Celular/genética , Ciclina D1/metabolismo , RNA Helicases DEAD-box/metabolismo , Feminino , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Imidazóis/farmacologia , Células MCF-7 , Microscopia de Fluorescência , Piperazinas/farmacologia , Interferência de RNA , Ribonuclease III/metabolismo , Transdução de Sinais/genética , Esferoides Celulares/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
Background: The prognostic value of an effective biomarker, pan-immune-inflammation value (PIV), for head and neck squamous cell carcinoma (HNSCC) patients after radical surgery or chemoradiotherapy has not been well explored. This study aimed to construct and validate nomograms based on PIV to predict survival outcomes of HNSCC patients. Methods: A total of 161 HNSCC patients who underwent radical surgery were enrolled retrospectively for development cohort. The cutoff of PIV was determined using the maximally selected rank statistics method. Multivariable Cox regression and least absolute shrinkage and selection operator (LASSO) regression analyses were performed to develop two nomograms (Model A and Model B) that predict disease-free survival (DFS). The concordance index, receiver operating characteristic curves, calibration curves, and decision curve analysis were used to evaluate the nomograms. A cohort composed of 50 patients who received radiotherapy or chemoradiotherapy (RT/CRT) alone was applied for generality testing of PIV and nomograms. Results: Patients with higher PIV (≥123.3) experienced a worse DFS (HR, 5.01; 95% CI, 3.25-7.72; p<0.0001) and overall survival (OS) (HR, 5.23; 95% CI, 3.34-8.18; p<0.0001) compared to patients with lower PIV (<123.3) in the development cohort. Predictors of Model A included age, TNM stage, neutrophil-to-lymphocyte ratio (NLR), and PIV, and that of Model B included TNM stage, lymphocyte-to-monocyte ratio (LMR), and PIV. In comparison with TNM stage alone, the two nomograms demonstrated good calibration and discrimination and showed satisfactory clinical utility in internal validation. The generality testing results showed that higher PIV was also associated with worse survival outcomes in the RT/CRT cohort and the possibility that the two nomograms may have a universal applicability for patients with different treatments. Conclusions: The nomograms based on PIV, a simple but useful indicator, can provide prognosis prediction of individual HNSCC patients after radical surgery and may be broadly applicated for patients after RT/CRT alone.
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The incidence of papillary thyroid microcarcinoma ï¼PTMCï¼ increases rapidly. However, epidemiological and autopsy studies show that the prevalence of low-risk papillary thyroid microcarcinoma ï¼LR-PTMCï¼ is very high, but the mortality is very low. There is over-diagnosis and over-treatment for LR-PTMC. Active surveillance ï¼ASï¼ was adopted for LR-PTMCs instead of immediate surgery, and more than 70% of the lesions remained stable or shrank in clinical observation. Therefore, AS is recommended for LR-PTMCs in clinical guidelines of several academic organizations around the world. However, PTMC is not equal to low-risk cancer. The implementation of AS strategy requires a strict grasp of indications and full consideration of population characteristics to ensure the maximum benefit of patients. This paper summarizes the present clinical progress of active surveillance for adult LR-PTMC.
Assuntos
Carcinoma Papilar , Neoplasias da Glândula Tireoide , Humanos , Adulto , Conduta Expectante , Neoplasias da Glândula Tireoide/patologia , Carcinoma Papilar/patologia , Incidência , Tireoidectomia/efeitos adversos , Estudos RetrospectivosRESUMO
Background: Metastatic colorectal cancer (mCRC) is a heterogeneous disease, often associated with poor outcomes and resistance to therapies. The racial variations in the molecular and microbiological profiles of mCRC patients, however, remain under-explored. Methods: Using RNA-SEQ data, we extracted and analyzed actively transcribing microbiota within the tumor milieu, ensuring that the identified bacteria were not merely transient inhabitants but engaged in the tumor ecosystem. Also, we independently acquired samples from 12 mCRC patients, specifically, 6 White individuals and 6 of Black or African American descent. These samples underwent 16S rRNA sequencing. Results: Our study revealed notable racial disparities in the molecular signatures and microbiota profiles of mCRC patients. The intersection of these data showcased the potential modulating effects of specific bacteria on gene expression. Particularly, the bacteria Helicobacter cinaedi and Sphingobium herbicidovorans emerged as significant influencers, with strong correlations to the genes SELENBP1 and SNORA38, respectively. Discussion: These findings underscore the intricate interplay between host genomics and actively transcribing tumor microbiota in mCRC's pathogenesis. The identified correlations between specific bacteria and genes highlight potential avenues for targeted therapies and a more personalized therapeutic approach.
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TRG-AS1 has been proved to inhibit cancer progression, whereas its effect on bone metastases of breast cancer is unknown. In this study, we determined breast cancer patients with disease free survival is longer in breast cancer patients with high TRG-AS1 expression. Moreover, TRG-AS1 was downregulated in breast cancer tissues and even lower in bone metastatic tumor tissues. Compared with parental breast cancer cell MDA-MB-231, TRG-AS1 expression was downregulated in MDA-MB-231-BO cells with strong bone-metastatic characteristics. Next, the binding sites of miR-877-5p on TRG-AS1 and WISP2 mRNA were predicted and result showed that miR-877-5p could bind to 3'UTR of TRG-AS1 and WISP2. Subsequently, BMMs and MC3T3-E1 cells were cultured in the conditioned media of MDA-MB-231 BO cells transfected with TRG-AS1 overexpression vector, shRNA and/or miR-877-5p mimics or inhibitor and/or overexpression vector and small interfering RNA of WISP2. TRG-AS1 silencing or miR-877-5p overexpression promoted MDA-MB-231 BO cell proliferation and invasion. TRG-AS1 overexpressing reduced TRAP positive cells, decreased TRAP, Cathepsin K, c-Fos, NFATc1 and AREG expression in BMMs, and promoted OPG, Runx2 and Bglap2 expression, and decreased RANKL expression in MC3T3-E1 cells. Silencing WISP2 rescued the effect of TRG-AS1 on BMMs and MC3T3-E1 cells. In vivo results showed that tumor volumes significantly decreased in mice injected with LV-TRG-AS1 transfected MDA-MB-231 cells. TRG-AS1 knockdown markedly reduced the number of TRAP+ cells and the percentage of Ki-67+ cells and decreased E-cadherin expression in xenograft tumor mice. In summary, TRG-AS1 acts an endogenous RNA, inhibited breast cancer bone metastasis by competitively binding with miR-877-5p to upregulate WISP2 expression.
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Neoplasias da Mama , MicroRNAs , RNA Longo não Codificante , Animais , Feminino , Humanos , Camundongos , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica/genética , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genéticaRESUMO
Papillary thyroid carcinoma (PTC) is the most common subtype of thyroid carcinoma. Despite a good prognosis, approximately a quarter of PTC patients are likely to relapse. Previous reports suggest an association between S-phase kinase-associated protein 2 (SKP2) and the prognosis of thyroid cancer. SKP1 is related to apoptosis of PTC cells; however, its role in PTC remains largely elusive. This study aimed to understand the expression and molecular mechanism of SKP2 in PTC. SKP2 expression was upregulated in PTC tissues and closely associated with clinical diagnosis. In vitro and in vivo knockdown of SKP2 expression in PTC cells suppressed cell growth and proliferation and induced apoptosis. SKP2 depletion promoted cell autophagy under glucose deprivation. SKP2 interacted with PH domain leucine-rich repeat protein phosphatase-1 (PHLPP1), triggering its degradation by ubiquitination. Furthermore, SKP2 activates the AKT-related pathways via PHLPP1, which leads to the cytoplasmic translocation of SKP2, indicating a reciprocal regulation between SKP2 and AKT. In conclusion, the upregulation of SKP2 leads to PTC proliferation and survival, and the regulatory network among SKP2, PHLPP1, and AKT provides novel insight into the molecular basis of SKP2 in tumor progression.
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Proteínas Proto-Oncogênicas c-akt , Neoplasias da Glândula Tireoide , Humanos , Apoptose/fisiologia , Autofagia/fisiologia , Linhagem Celular Tumoral , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , Proteínas Nucleares/metabolismo , Fosfoproteínas Fosfatases/genética , Fosfoproteínas Fosfatases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Quinases Associadas a Fase S/genética , Proteínas Quinases Associadas a Fase S/metabolismo , Câncer Papilífero da Tireoide/genética , Câncer Papilífero da Tireoide/patologia , Neoplasias da Glândula Tireoide/patologia , UbiquitinaçãoRESUMO
OBJECTIVE: This study evaluated the feasibility, stability, safety, and economy of cricothyroid membrane (CM)-inserted needle electrodes for recurrent laryngeal nerve monitoring. STUDY DESIGN: Parallel and controlled study. SETTING: Clinical research center for thyroid diseases of Shaanxi province. METHODS: A total of 64 patients in the needle electrodes group (104 recurrent laryngeal nerves [RLNs]) and 44 patients in the endotracheal tube (ETT)-based electrodes group (80 RLNs) underwent monitored thyroidectomy. The evoked electromyography (EMG) signals detected by the 2 electrodes were recorded and analyzed. The changes in EMG during Berry's ligament traction and tracheal displacement were compared. All patients underwent preoperative and postoperative laryngoscopy within 1 week. RESULTS: Both electrodes successfully recorded typical evoked laryngeal EMG waveforms from RLNs. The needle electrodes recorded relatively higher amplitudes and similar latencies compared to ETT-based electrodes. The evoked EMG signals attributed to needle electrodes could accurately predict the function of RLNs with 100% sensitivity and specificity. The reduction in the recorded amplitudes attributed to needle electrodes was higher than that observed with ETT-based electrodes during Berry's ligament traction or trachea displacement, whereas a similar increase in the latencies was recorded in the 2 groups. Particularly, Berry's ligament traction was more likely to lead to EMG amplitude reduction and latency prolongation. The needle electrodes group recorded 2 cases of minor bleeding on the CM. The needle electrodes were more cost-effective than ETT-based electrodes. CONCLUSION: The CM-inserted needle electrodes are feasible, stable, safe, and economical for RLN monitoring, and they provide an alternative novel intraoperative neural monitoring format for thyroid surgeons.
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Glândula Tireoide , Tireoidectomia , Humanos , Glândula Tireoide/cirurgia , Estudos de Viabilidade , Monitorização Intraoperatória , Nervo Laríngeo Recorrente , Eletrodos , EletromiografiaRESUMO
BACKGROUND: The incidence of thyroid cancer is rising rapidly in China, but there are few studies on the risk factors of thyroid cancer in the Chinese Han population. METHODS: We performed this case-control study of 510 patients and 509 controls to for determine the linkage of VAV3 variants (rs17019602, rs7521681, rs4915076, and rs1777451) with thyroid cancer susceptibility by computing the odds ratio (OR) and 95% confidence intervals (CI). Multi-factor dimension reduction (MDR) analysis was conducted to assess interaction of VAV3 genetic variants. RESULTS: We found that rs7521681 was remarkably related to a higher risk of thyroid cancer (OR = 1.74, p = 0.012), whereas rs4915076 (OR = 0.66, p = 0.001) significantly decreased thyroid cancer susceptibility. Stratified analyses showed that rs4915076 had a protective role in thyroid cancer in both ages >45 years (OR = 0.70, p = 0.017) and age ≤45 years (OR = 0.63, p = 0.007). Rs17019602 could increase the susceptibility of thyroid cancer in men (OR = 4.76, p = 0.049). Rs7521681 was related to an increased risk of thyroid cancer in women (OR = 1.97, p = 0.012). Rs4915076 could protect individuals from thyroid cancer both in men (OR = 0.60, p = 0.031) and women (OR = 0.68, p = 0.010). Moreover, rs4915076 was the best single-locus model to predict thyroid cancer. Interestingly, the interaction model of rs17019602, rs7521681, rs4915076, rs1777451, and age was a candidate gene-environment model. CONCLUSION: Our results indicated VAV3 variants were associated with thyroid cancer, which provides a new sight into etiology of thyroid cancer.
Assuntos
Predisposição Genética para Doença , Neoplasias da Glândula Tireoide , Adulto , Alelos , Estudos de Casos e Controles , China/epidemiologia , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-vav/genética , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/genéticaRESUMO
Nasopharyngeal carcinoma occurs in many parts of the pars nasalis pharyngis, and the pathological type is mainly squamous cell carcinoma. Because of the special position of nasopharynx, breathing, pronunciation and daily life will be seriously affected. At present, the research direction of nasopharyngeal carcinoma is mainly to explore the law of tumor cell proliferation and migration, study the molecular mechanism, master its biological behavior and clinical significance, try to find therapeutic targets, and further improve the level of tumor treatment. However, the pathologic structure and molecular mechanism of nasopharyngeal carcinoma have not been fully elucidated. In this study, the Lentivirus-mediated EIF3C shRNA vector (L.V-shEIF3C) was constructed to down-regulate the expression of EIF3C in human pharyngeal squamous carcinoma cell FaDu and the human nasopharyngeal carcinoma cell 5-8F, it was found that down-regulation of EIF3C could significantly inhibit the cell proliferation, promote cell apoptosis, induce cell cycle arrest, and inhibit the formation and growth of tumors in mouse models. This study provides strong evidence that EIF3C is a key gene driving the development and progression of head and neck cancer, which is of great significance for the diagnosis, prognosis or treatment of tumors, suggesting that EIF3C may become a valuable therapeutic development and intervention target.