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BACKGROUND/AIMS: High expression in hepatocellular carcinoma (HEIH) is an long noncoding RNA (lncRNA) which is highly expressed in hepatocellular carcinoma (HCC). Aberrant expression of HEIH is implicated in regulating HCC cells growth and metastasis. This study attempted to illustrate the effects of HEIH on HCC cell lines. METHODS: The expression changes of HEIH in HCC tumor tissues and the paracancerous tissues derived from 20 patients with HCC were tested. Effects of HEIH on Huh7 and Hep3B cells viability, apoptosis, migration, and invasion were assessed by silencing HEIH in vitro. Furthermore, downstream effector and signaling of HEIH were studied. RESULTS: As compared with the paracancerous tissues, the HEIH expression was highly expressed in tumor tissues. Silence of HEIH significantly reduced Huh7 and Hep3B cells viability, migration, and invasion, but induced apoptosis. It was coupled with the downregulated CyclinD1, Bcl-2, MMP-2, MMP-8, Vimentin, the upregulated p53, Bax, as well as the cleaved caspase-3. MicroRNA (miR)-199a-3p was identified as a downstream effector of HEIH, as its expression was upregulated by HEIH silence, and the functional effects of HEIH on Huh7 and Hep3B cells were all attenuated when miR-199a-3p expression was suppressed. Furthermore, HEIH silence suppressed the activation of mTOR signaling via upregulating miR-199a-3p. CONCLUSION: HEIH silence might be a promising target for suppressing HCC cells growth and metastasis. Silence of HEIH exerted its antitumor properties possibly through upregulating miR-199a-3p, and thereby blockage of mTOR signaling.
Assuntos
Inativação Gênica , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/patologia , MicroRNAs/metabolismo , RNA Longo não Codificante/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Adulto , Idoso , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , RNA Longo não Codificante/genéticaRESUMO
Antisense non-coding RNA in the INK4A locus (ANRIL) has been recognized as a cancer-related lncRNA in hepatocellular carcinoma previously. This study aimed to reveal the functional effects and mechanisms of ANRIL on hepatocellular carcinoma cells in vitro. The expression of ANRIL in hepatocellular carcinoma cell lines (MHCC97 and Li-7) and non-tumourigenic liver cell line THLE-3 was detected by qRT-PCR. The expression of ANRIL, miR-144 and PBX3 in hepatocellular carcinoma cells was altered simultaneously or respectively by vector/oligonucleotide transfection. Then, cell viability, migration, invasion, apoptotic cell rate, protein expression of apoptosis-related factors were assessed. The correlation between ANRIL, miR-144 and PBX3 was explored. ANRIL was highly expressed in MHCC97 and Li-7 cells when compared to THLE-3 cells. ANRIL overexpression promoted cell viability, migration, invasion and suppressed apoptosis of MHCC97 and Li-7 cells. ANRIL negatively regulated miR-144, and oncogenic effects of ANRIL were attenuated when miR-144 was overexpressed. PBX3 was a direct target of miR-144. miR-144 overexpression blocked PI3K/AKT and JAK/STAT signalling pathways via targeting PBX3. Our data documented that ANRIL promoted hepatocellular carcinoma cells growth, migration and invasion. One of the possible mechanisms responsible for the tumour-promoting actions is that ANRIL sponging miR-144 to derepress PBX3.
Assuntos
Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Apoptose/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , Sobrevivência Celular/genética , Inibidor p16 de Quinase Dependente de Ciclina/genética , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/genética , Humanos , Janus Quinases/genética , Janus Quinases/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , RNA Antissenso/genética , Fatores de Transcrição STAT/genética , Fatores de Transcrição STAT/metabolismoRESUMO
MicroRNA (miR)-494 has been identified as a predictor and inhibitor in pancreatic cancer. This study aimed to explore the role of miR-494 in pancreatic cancer cells, and the regulation of glioma-associated oncogene 3 (Gli3) by miR-494. The mRNA level of Gli3 in 99 pairs of pancreatic cancer and correspondingly adjacent tissues was monitored by qRT-PCR. Correlation of Gli3 expression with miR-494 level was assessed by Pearson χ2 test. Dual-luciferase reporter assay was used to detect whether Gli3 was a target of miR-494. Following miR-494 mimics and miR-494 inhibitor transfection, the changes in cell viability and migration were detected by using CCK-8 and Transwell chamber. Furthermore, Gli3 siRNA was co-transfected with miR-494 inhibitor, and then cell viability and migration were redetected. Result showed that, the mRNA level of Gli3 in tumor tissues was higher than in the adjacent tissues (P < 0.01). There were 45 in 99 patients with pancreatic cancer expressed Gli3, and significant correlations were observed between the Gli3 level and vascular invasion (P = 0.04), distant metastasis (P = 0.001), and histologic grade (P = 0.03). Gli3 was a direct target of miR-494 (P < 0.01) and it was negatively related by miR-494 (P < 0.01). Overexpression of miR-494 suppressed PANC-1 cells viability (P < 0.05, P < 0.01, or P < 0.001) and migration (P < 0.01). Additionally, Gli3 silence suppresses miR-494 suppression-induced cell viability and migration (P < 0.01). In conclusion, these data demonstrate miR-494 exhibits tumor-suppressive effects on pancreatic cancer, possibly via targeting Gli3.
Assuntos
Biomarcadores Tumorais/metabolismo , Movimento Celular , Proliferação de Células , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Proteínas do Tecido Nervoso/metabolismo , Neoplasias Pancreáticas/patologia , Proteína Gli3 com Dedos de Zinco/metabolismo , Apoptose , Biomarcadores Tumorais/genética , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Metástase Neoplásica , Proteínas do Tecido Nervoso/genética , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Prognóstico , Células Tumorais Cultivadas , Proteína Gli3 com Dedos de Zinco/genéticaRESUMO
Neuroendocrine tumors represent a rare neoplastic entity, with even rarer occurrences within the biliary tract system. The pathogenesis of such conditions remains enigmatic. Clinical manifestations and radiological evaluations exhibit limited specificity, rendering preoperative diagnoses challenging. As of now, definitive therapeutic modalities remain elusive. Surgical excision stands as the paramount approach for managing biliary neuroendocrine tumors. A thorough preoperative assessment should precede the formulation of a judicious surgical strategy. Postoperative targeted adjuvant therapies hold promise in enhancing therapeutic efficacy and retarding tumor recurrence. This article chronicles a case study detailing a neuroendocrine tumor's diagnostic and treatment course within the perihilar bile duct. Integrating pertinent literature, it encapsulates the clinical attributes and diagnostic and therapeutic advancements in biliary neuroendocrine tumors. The aspiration is to augment awareness of this category of ailments, mitigating the occurrence of both missed and erroneous diagnoses, and furnishing a reference for forthcoming clinical endeavors.
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Hepatocellular carcinoma (HCC) ranks as the sixth most common malignancy globally, with the majority of patients presenting at the initial diagnosis with locally advanced or metastatic disease, precluding the opportunity for curative surgical intervention. With the exploration and advancement of locoregional treatments, novel molecular-targeted therapies, anti-angiogenic agents, and immunomodulatory drugs, the management of HCC has seen an increase in objective response rates and prolonged duration of response significantly enhancing the potential for conversion to resectable disease in intermediate and advanced-stage unresectable HCC. Herein, we present a case of Barcelona Clinic Liver Cancer stage B unresectable HCC, where after two courses of treatment with transarterial chemoembolization combined with atezolizumab plus bevacizumab significant tumor reduction was achieved. Per Response Evaluation Criteria in Solid Tumors 1.1, partial response culminated in successful curative surgical resection. No drug-related adverse reactions occurred during hospitalization, and there has been no recurrence during the 11-month postoperative follow-up. For patients with Barcelona Clinic Liver Cancer stage B (intermediate-stage) unresectable HCC, the transarterial chemoembolization combined with atezolizumab plus bevacizumab regimen may offer improved therapeutic outcomes leading to a higher success rate of conversion therapy and, thus, improved survival.
Assuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/tratamento farmacológico , Bevacizumab/administração & dosagem , Bevacizumab/uso terapêutico , Quimioembolização Terapêutica/métodos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Masculino , Estadiamento de Neoplasias , Pessoa de Meia-Idade , Resultado do Tratamento , Terapia CombinadaRESUMO
We aimed to confirm whether transmembrane serine protease 2 (TMPRSS2) regulates nidogen 1 (NID1) expression in extracellular vesicles (EVs) and metastatic hepatocellular carcinoma (HCC) cells. HCC cells, HUVEC cells, MRC-5 cells, HLE cells, MHCCLM3 cells, MHCC97L cells, H2P cells, H2M cells, as well as LO2 cells were cultured according to providers' instruction and EV models were established by using BALB/cAnN-nu mice to facilitate the verifications. We found that TMPRSS2 expression was inversely correlated with the metastatic potential of HCC cell lines. The expression of TMPRSS2 decreased in a time-dependent manner in tumor-bearing model mice implanted with MHCCLM3 cells compared with uninoculated mice. TMPRSS2 overexpression in MHCCLM3 and MHCC97L cells led to the significant downregulation of NID1 expression in total cell lysates and isolated EVs. In contrast, TMPRSS2 silencing resulted in the elevation of NID1 expression in cells and EVs. Administration of EVs from MHCCLM3 and MHCC97L cells with overexpressed or silenced TMPRSS2 inhibited or strengthened, respectively, the invasion, proliferation, and migration of LO2 tumor cells. EVs derived from MHCCLM3 and MHCC97L cells with overexpressed or depleted TMPRSS2 also deactivated or activated fibroblasts, respectively. These EVs secrete inflammatory cytokines and phosphorylated p65, facilitate the colonization of fibroblasts, and augment fibroblast growth and motility. These findings provide evidence for a new candidate drug targeting tumorigenic EV-NID1 to treat HCC.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Animais , Camundongos , Carcinoma Hepatocelular/patologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , Serina Proteases/metabolismo , Serina Proteases/uso terapêuticoRESUMO
Pancreatic cancer (PC) is one of the most common malignant tumors in the world with a poor prognosis. There were limited studies investigating the genetic signatures associated with inflammatory responses, tumor microenvironment (TME), and tumor drug sensitivity prediction. In the Cancer Genome Atlas (TCGA) dataset, we constructed an inflammatory response-related genes prognostic signature for PC, and predictive ability of the model was assessed via the International Cancer Genome Consortium (ICGC) database. Then, we explored the differences of TME, immune checkpoint genes and drug resistance genes, and the cancer cell sensitivity to chemotherapy drugs between different risk score group. Based on the TCGA and ICGC databases, we constructed and validated a prognostic model, which consisted of 5 genes (including AHR, F3, GNA15, IL18, and INHBA). Moreover, the prognostic model was independent prognostic factors affecting overall survival (OS). The low-risk score group had better OS, and lower stromal score, compared with patients in the high-risk score group. The difference of antigen-presenting cells, T cell regulation, and drug resistance genes between different risk score groups was found. In addition, the immune checkpoint genes were positively correlation to risk score. The expression levels of AHR, GNA15, IL18, and INHBA were related to the sensitivity of anti-tumor chemotherapy drugs. Gene set enrichment analysis (GSEA) showed significant pathway such as calcium signaling pathway and p53 signaling pathway. We successfully constructed a 5-inflammatory response-related gene signature to predict survival, TME, and cancer cell sensitivity to chemotherapy drugs in PC patients. Furthermore, substantiation was warranted to verify the role of these genes in tumorigenesis.
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Interleucina-18 , Neoplasias Pancreáticas , Humanos , Carcinogênese , Neoplasias Pancreáticas/genética , Microambiente Tumoral , Neoplasias PancreáticasRESUMO
Primary hepatic adenosquamous carcinoma is considered a rare subtype of intrahepatic cholangiocarcinoma, with fewer than 100 domestic and international cases reported. This malignancy exhibits a high degree of malignancy, strong invasiveness, and an unfavorable prognosis due to its propensity for early lymph node and intrahepatic metastasis. The etiology of this disease remains uncertain, and preoperative diagnosis is exceedingly challenging owing to the nonspecific clinical features and lack of specificity in imaging studies. Radical surgical resection is the most effective treatment for non-metastatic tumors, while targeted adjuvant therapy administered postoperatively can enhance therapeutic efficacy and delay tumor recurrence. This article documents the diagnostic and therapeutic course of a case of primary hepatic adenosquamous carcinoma treated at our medical institution, along with a comprehensive synthesis of the clinical characteristics and advances in the diagnosis and treatment of this disease, aiming to augment understanding and serve as a reference for future clinical endeavors.
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Pancreatic cancer (PC) has a dismal prognosis despite advancing scientific and technological knowledge. The exploration of novel genes is critical to improving current therapeutic measures. This research is aimed at selecting hub genes that can act as candidate therapeutic target genes and as prognostic biomarkers in PC. Gene expression profiles of datasets GSE101448, GSE15471, and GSE62452 were extracted from the GEO database. The "limma" package was performed to select differentially expressed genes (DEGs) between PC and normal tissue samples in each dataset. Robust rank aggregation (RRA) algorithm was conducted to integrate multiple expression profiles and identify robust DEGs. GO analysis and KEGG analysis were conducted to identify the functional correlation of the DEGs. The CIBERSORT algorithm was conducted to estimate the immune cell composition of each tissue sample. STRING and Cytoscape were used to establish the protein-protein interaction (PPI) network. The cytoHubba plugin in Cytoscape was performed to identify hub genes. Survival analysis based on hub gene expression was performed with clinical information from TCGA database. 566 robust DEGs (338 upregulated genes and 226 downregulated genes) were identified. Tumor tissue had a higher infiltration of resting dendritic cells and tumor-associated macrophages (TAM), including M0, M1, and M2 macrophages, while infiltration levels of B memory cells, plasma cells, T cells CD8, T follicular helper cells, and NK cells in normal tissue were relatively higher. GO terms and KEGG pathway analysis results revealed enrichment in tumor-associated pathways, including the extracellular matrix organization, cell-substrate adhesion cytokine-cytokine receptor interaction, calcium signaling pathway, and glycine, serine, and threonine metabolism, to name a few. Finally, FN1, MSLN, PLAU, and VCAN were selected as hub genes. High expression of FN1, MSLN, PLAU, and VCAN in PC significantly correlated with poor prognosis. Integrated transcriptomic analysis was used to provide new insights into PC pathogenesis. FN1, MSLN, PLAU, and VCAN may be considered as novel biomarkers of PC.
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Neoplasias Pancreáticas , Transcriptoma , Biomarcadores Tumorais/genética , Biologia Computacional/métodos , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pancreáticas/genética , Neoplasias PancreáticasRESUMO
Brassica napus (AACC genome) is an important oilseed crop that was formed by the fusion of the diploids B. rapa (AA) and B. oleracea (CC). The complete genomic sequence of the Brassica A genome will be available soon from the B. rapa genome sequencing project, but it is not clear how informative the A genome sequence in B. rapa (A(r)) will be for predicting the structure and function of the A subgenome in the allotetraploid Brassica species B. napus (A(n)). In this paper, we report the results of structural and functional comparative mapping between the A subgenomes of B. napus and B. rapa based on genetic maps that were anchored with bacterial artificial chromosomes (BACs)-sequence of B. rapa. We identified segmental conservation that represented by syntenic blocks in over one third of the A genome; meanwhile, comparative mapping of quantitative trait loci for seed quality traits identified a dozen homologous regions with conserved function in the A genome of the two species. However, several genomic rearrangement events, such as inversions, intra- and inter-chromosomal translocations, were also observed, covering totally at least 5% of the A genome, between allotetraploid B. napus and diploid B. rapa. Based on these results, the A genomes of B. rapa and B. napus are mostly functionally conserved, but caution will be necessary in applying the full sequence data from B. rapa to the B. napus as a result of genomic rearrangements in the A genome between the two species.
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Brassica napus/genética , Brassica rapa/genética , Mapeamento Cromossômico , Cromossomos de Plantas/genética , Sequência de Bases , Cromossomos Artificiais Bacterianos , DNA de Plantas , Evolução Molecular , Ligação Genética , Genoma de Planta , Locos de Características Quantitativas , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be a threat, causing economically significant impacts on the swine industry worldwide. Unfortunately, the traditional control strategies and conventional vaccines fail to provide sustainable disease control, in particular against genetically diverse strains, as they suffer from both antigenic heterogeneity and various immune evasion strategies of PRRSV. In this paper, latest research progress in immunology and immune evasion of PRRSVis summarized to provide a referenc for PRSSV prevention and control as well as the design of new vaccines.