RESUMEN
Anoikis resistance is a fundamental feature of the survival of metastatic cancer cells during cancer progression. However, the mechanisms underlying anoikis resistance in pancreatic cancer (PC) are still unclear. MicroRNA-137 (miR-137) is a tumor suppressor that inhibits the proliferation and invasion of cancer cells through targeting multiple oncogenes. However, the effects and molecular mechanism of miR-137 on anoikis of PC are still unclear. Here we demonstrated that miR-137 was downregulated after the induction of anoikis model in time dependent. Function assays revealed that miR-137 promoted the pancreatic cancer cells anoikis in vitro and vivo. According to bioinformation analysis of clinical databases, we predicted that paxillin (PXN) was a target of miR-137. Further, TCGA analysis revealed that PXN was closely associated with the development of PC. Through loss-of-function studies, we demonstrated that PXN was a functional target of miR-137 on anoikis of PC cells. Moreover, we found that PXN promoted the activation of the AKT signaling pathways which was involving in the cancer cells anoikis. Together, our findings reveal that miR-137 plays a novel role during anoikis and may serve as a potential target for the detection and treatment of PC.
RESUMEN
Alcoholassociated hepatocellular carcinoma (HCC) is a subtype of HCC with poor prognosis. The present study aimed to identify key biomarkers for alcoholassociated HCC. The gene data profiles and corresponding clinical traits of patients with alcoholassociated HCC were downloaded from The Cancer Genome Atlas (TCGA) database. Firstly, good genes and good samples were identified, which were subsequently used to conduct weighted gene coexpression network analysis (WGCNA). Hub genes in the significant modules were selected following Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and from constructing a proteinprotein interaction (PPI) network. Real hub genes among hub genes were determined following progression, survival analysis and gene set enrichment analysis (GSEA), as well as reverse transcriptionquantitative PCR and immunohistochemical staining of nonalcohol and alcoholassociated HCC samples. In total, 64 good samples of alcoholassociated HCC with height score <160 were selected, from which 15,195 good genes were identified and used to conduct WGCNA; 8 gene coexpressed modules were identified using WGCNA, while 3 modules (including pink, magenta and turquoise) were significantly associated with ChildPugh score, Tstage and body weight. Following GO and KEGG analysis and construction of the PPI network, a total of 30 hub genes were identified in the aforementioned 3 gene coexpressed modules, while 16 hub genes (including AURKB, BUB1, BUB1B, CCNB1, CCNB2, CDC20, CDCA8, CDK1, PLK1, RPS5, RPS7, RPS8, RPS14, RPS27, RPSA and TOP2A) were associated with the development of alcoholassociated HCC, and had a significant prognosis value. Among these genes, only RPS8 was highly expressed in alcoholassociated HCC, but not in nonalcoholassociated HCC, while RPS5 was not significantly associated in either alcohol or nonalcoholassociated HCC. GSEA demonstrated that 10 pathways, including RNA polymerase and ribosome pathways were enriched in alcoholassociated HCC samples where RPS8 was highly expressed. Taken together, the results of the present study demonstrate that RPS8 may be a novel biomarker for the diagnosis of patients with alcoholassociated HCC.
Asunto(s)
Consumo de Bebidas Alcohólicas/efectos adversos , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/diagnóstico , Neoplasias Hepáticas/diagnóstico , Proteínas Ribosómicas/genética , Adulto , Anciano , Consumo de Bebidas Alcohólicas/patología , Carcinoma Hepatocelular/etiología , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Estudios de Casos y Controles , Biología Computacional , Conjuntos de Datos como Asunto , Progresión de la Enfermedad , Femenino , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Redes Reguladoras de Genes , Humanos , Hígado/patología , Neoplasias Hepáticas/etiología , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Pronóstico , Mapas de Interacción de Proteínas/genética , Análisis de SupervivenciaRESUMEN
PURPOSE: The objective of this study was to analyze the clinical features and prognosis of gastroenteropancreatic (GEP) neuroendocrine carcinomas (NECs) with liver metastasis and primary hepatic neuroendocrine carcinomas (PHNECs), as these rare hepatic neuroendocrine carcinomas have not been exhaustively studied. METHODS: The clinical data of 47 patients with hepatic NECs were retrospectively reviewed and categorized to analyze features and prognosis. RESULTS: The 47 studied cases comprised 13 cases of primary hepatic NECs (primary group) and 34 cases of metastatic hepatic NECs (metastatic group). Male patients were slightly dominant in both groups, while no age predilection was present. PHNECs were mostly single nodules located in the right lobe of the liver. Metastatic hepatic NECs originated mostly from the pancreas and stomach without distinction of the lobes of the liver. Univariate analysis showed that the treatment protocol (radical operation or others) was correlated with the overall survival (OS; p < 0.05) in the primary group, while treatment protocol and cytokeratin 7 (CK7) were associated with OS (p < 0.05) in the metastatic group. Cox proportional hazard regression showed that radical operation was an independent prognostic factor (p < 0.05) for OS in the metastatic group. CONCLUSIONS: No significant differences in the clinicopathological features between PHNECs and metastatic hepatic GEP NECs were found, but radical operation was significantly correlated with OS for both carcinomas. Radical operation is the first choice for patients who are eligible for operation.
Asunto(s)
Carcinoma Neuroendocrino/patología , Neoplasias Intestinales/patología , Neoplasias Hepáticas/patología , Tumores Neuroendocrinos/patología , Neoplasias Pancreáticas/patología , Nódulo Pulmonar Solitario/patología , Neoplasias Gástricas/patología , Adulto , Anciano , Carcinoma Neuroendocrino/cirugía , Femenino , Humanos , Neoplasias Intestinales/cirugía , Neoplasias Hepáticas/secundario , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Tumores Neuroendocrinos/cirugía , Neoplasias Pancreáticas/cirugía , Pronóstico , Estudios Retrospectivos , Nódulo Pulmonar Solitario/cirugía , Neoplasias Gástricas/cirugía , Análisis de SupervivenciaRESUMEN
BACKGROUND: The molecular mechanisms involved in the development and metastasis of hepatocellular carcinoma (HCC) are complex. Molecule-targeted drugs are characterized by strong specificity and low toxicity, but the clinical research of these drugs still exhibits many difficulties, such as poor target specificity. With the in-depth study of the tumor immunological theory, therapies based on overcoming the tumor immune escape to produce a specific effective tumor immune response has gradually become a hot topic in tumor research. We hope that by studying the effects of liver-targeted drugs on the expression of immune-related proteins in hepatocellular carcinoma cells, we will find a potential link to further guide the clinical drug use. METHODS: Human hepatoma Hep3B cells were used to establish liver cancer xenografts by inoculating 40 BALB/c nude mice. The following five groups of mice (8 mice per group) were randomly set up: lenvatinib group, apatinib group, sorafenib group, regorafenib group, and dimethyl sulfoxide (DMSO) group. After treatment, we analyzed PD-L1 and B7-H3 mRNA using the real-time polymerase chain reaction (PCR) assay and assessed the PD-L1 and B7-H3 protein expression by Western immunoblotting. RESULTS: Real-time PCR results suggested that the mRNA expression of PD-L1 in the lenvatinib group was significantly higher than that in the control group, while its expression in the regorafenib group was significantly lower than that in the control group (both pâ¯<â¯.05). Western immunoblotting results suggested that, compared with the control group, PD-L1 protein was increased in the lenvatinib group, while its expression in the regorafenib group was decreased. CONCLUSION: Lenvatinib and regorafenib affected the expression of PD-L1 in the process of anti-HCC.