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1.
J Cell Mol Med ; 24(7): 4136-4149, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32100443

RESUMO

The aim of this study was to explore the molecular mechanism of lncRNA POU6F2-AS2 in proliferation and drug resistance of colon cancer. Total paired 70 colon cancer and adjacent normal tissues were collected from colon cancer patients. Colon cancer and normal colonic epithelial cells were purchased. POU6F2-AS2 was up- or down-expressed by vectors. LC50 of all cell lines before and after transfection with these plasmids was detected. qRT-PCR was used to detect the expression of POU6F2-AS2, miR-377 and BRD4 before or after transfection. In situ hybridization was also undertaken to detect the level of POU6F2-AS2. Different concentrations of 5-Fu (0, 1, 2.5, 5, 10, 20, 40 and 80 µg/mL) were used for 5-FU insensitivity assay. CCK-8 and crystal violet staining assay were used for detecting cell proliferation, and flow cytometry was used for identifying cell cycle distribution and apoptosis. In order to detect the fragmented DNA in apoptotic cells, TUNEL assay was used. RNA pull-down assay and luciferase reporter assay were used to verify the binding site. Rescue assay confirmed the subtractive effect of miR-377 inhibitors. POU6F2-AS2 was highly expressed in colon cancer, which was associated with clinical pathology. Up-regulated POU6F2-AS2 promoted cell proliferation and cell cycle of colon cancer cells. Overexpression of POU6F2-AS2 inhibited the expression of miR-377 and then up-regulated the expression of BRD4. Up-regulated BRD4 ultimately promoted cell proliferation and cell survival Down-regulated POU6F2-AS2 showed enhanced sensitivity of 5-FU. POU6F2-AS2 promoted cell proliferation and drug resistance in colon cancer by regulating miR-377/BRD4 gene.


Assuntos
Proteínas de Ciclo Celular/genética , Neoplasias do Colo/tratamento farmacológico , Fatores do Domínio POU/genética , RNA Longo não Codificante/genética , Fatores de Transcrição/genética , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Feminino , Fluoruracila/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HCT116 , Células HT29 , Humanos , Masculino
2.
Int J Mol Med ; 41(1): 155-163, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29115379

RESUMO

Gastric cancer (GC) is the third leading cause of cancer-related mortality in China and worlwide; hence, the identification of GC-related genes is necessary for the development of effective treatment strategies. In this study, histone deacetylase 3 (HDAC3) was identified as the most significantly upregulated cancer-related gene in GC tissues by microarray. In accordance with this, HDAC3 expression was found to be upregulated in GC cell lines/tissues. Further experiments indicated that the knockdown of HDAC3 decreased GC cell viability, reduced the colony formation number and decreased tumor weight. To explore the underlying mechanisms, the overexpression of HDAC3 was induced by transfection with an overexpression plasmid, followed by miRNA microarray, and we identified miR-454 as the most markedly upregulated miRNA. Accordingly, miR-454 expression was upregulated in GC cell lines/tissues and a high level of miR-454 indicated a high HDAC3 expression in GC tissues, and miR-454 knockdown reduced cell viability. In addition, a high level of miR-454 was significantly associated with an advanced clinical stage, lymph node metastases and a poor prognosis of patients with GC. Furthermore, CHD5 was identified as a direct target of miR-454. CHD5 was downregulated in GC tissues/cell lines and the expresssion of CHD5 inversely correlated with the level of miR-454 in GC tissues. Taken together, these observations indicate that HDAC3 is associated with GC cell growth via the miR-454-mediated targeting of CHD5.


Assuntos
Carcinogênese/genética , DNA Helicases/genética , Histona Desacetilases/genética , MicroRNAs/genética , Proteínas do Tecido Nervoso/genética , Neoplasias Gástricas/genética , Idoso , Animais , Apoptose/genética , Linhagem Celular Tumoral , Movimento Celular/genética , Proliferação de Células/genética , China , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Masculino , Camundongos , Pessoa de Meia-Idade , Neoplasias Gástricas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
3.
Gene ; 604: 33-40, 2017 Mar 10.
Artigo em Inglês | MEDLINE | ID: mdl-27998790

RESUMO

OBJECTIVE: To screen the gene signature for distinguishing patients with high risks from those with low-risks for colon cancer recurrence and predicting their prognosis. METHODS: Five microarray datasets of colon cancer samples were collected from Gene Expression Omnibus database and one was obtained from The Cancer Genome Atlas (TCGA). After preprocessing, data in GSE17537 were analyzed using the Linear Models for Microarray data (LIMMA) method to identify the differentially expressed genes (DEGs). The DEGs further underwent PPI network-based neighborhood scoring and support vector machine (SVM) analyses to screen the feature genes associated with recurrence and prognosis, which were then validated by four datasets GSE38832, GSE17538, GSE28814 and TCGA using SVM and Cox regression analyses. RESULTS: A total of 1207 genes were identified as DEGs between recurrence and no-recurrence samples, including 726 downregulated and 481 upregulated genes. Using SVM analysis and five gene expression profile data confirmation, a 15-gene signature (HES5, ZNF417, GLRA2, OR8D2, HOXA7, FABP6, MUSK, HTR6, GRIP2, KLRK1, VEGFA, AKAP12, RHEB, NCRNA00152 and PMEPA1) were identified as a predictor of recurrence risk and prognosis for colon cancer patients. CONCLUSION: Our identified 15-gene signature may be useful to classify colon cancer patients with different prognosis and some genes in this signature may represent new therapeutic targets.


Assuntos
Biomarcadores Tumorais/genética , Neoplasias do Colo/diagnóstico , Regulação Neoplásica da Expressão Gênica , Proteínas de Neoplasias/genética , Recidiva Local de Neoplasia/diagnóstico , Transcriptoma , Biomarcadores Tumorais/metabolismo , Neoplasias do Colo/genética , Neoplasias do Colo/mortalidade , Neoplasias do Colo/patologia , Redes Reguladoras de Genes , Humanos , Proteínas de Neoplasias/metabolismo , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/mortalidade , Recidiva Local de Neoplasia/patologia , Prognóstico , Mapeamento de Interação de Proteínas , Curva ROC , Máquina de Vetores de Suporte , Análise de Sobrevida
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