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1.
Mol Med Rep ; 22(4): 2723-2732, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32945458

RESUMO

Thyroid carcinoma (THCA) is a malignant tumor of the endocrine system. Previous studies have revealed the vital roles of microRNAs (miRNAs/miRs) in THCA procession. The present study aimed to explore the effects of miR­15b­5p on the progression of THCA and its targeting mechanism. The data of THCA and healthy samples were firstly collected from starbase2.0 and used to analyze the relationship of miR­15b­5p with THCA. Dual­luciferase assay was performed to detect the direct interaction between miR­15b­5p and the predicted target gene GDP dissociation inhibitor 2 (GDI2). The effects of miR­15b­5p and GDI2 on the overall survival of patients with THCA were analyzed using Kaplan­Meier analysis with log rank test. Cell Counting Kit­8 and Transwell assays were conducted to assess the impacts of miR­15b­5p and GDI2 on the proliferation and invasion of THCA cells. Reverse transcription­quantitative PCR and western blot analyses were performed to analyze the expression levels of the related miRNAs and proteins, respectively. miR­15b­5p was found to be downregulated both in THCA tissues and cells, and the low expression of miR­15b­5p was associated with the short overall survival time of patients. Moreover, the upregulation or downregulation of miR­15b­5p could inhibit or enhance the proliferation and invasion of THCA cells, respectively. miR­15b­5p reduced the protein expression levels of matrix metalloproteinase (MMP)2 and MMP9, which were related to cell invasion. Furthermore, GDI2, which was enhanced in THCA and related to the poor prognosis of patients with THCA, was identified as the target gene of miR­15b­5p and negatively regulated by miR­15b­5p. Additional experiments demonstrated that GDI2 overexpression could significantly reduce the antitumor effect of miR­15b­5p and its inhibitory action on the expression levels of MMP2 and MMP9. Thus, the results indicated a potential tumor suppressive role of miR­15b­5p in THCA, which was mainly exerted by targeting GDI2 and modulating MMP2 and MMP9. These findings will increase the understanding on the pathogenesis of THCA and provide novel candidates for THCA therapy.


Assuntos
Regulação para Baixo , Inibidores de Dissociação do Nucleotídeo Guanina/genética , MicroRNAs/genética , Neoplasias da Glândula Tireoide/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Análise de Sobrevida , Neoplasias da Glândula Tireoide/mortalidade , Adulto Jovem
2.
Naunyn Schmiedebergs Arch Pharmacol ; 393(11): 2177-2184, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32009213

RESUMO

Laryngeal squamous cell carcinoma (LSCC) is the most common type of laryngeal cancer with poor prognosis. In the present study, we aimed to investigate the biological role of long non-coding RNA OIP5-AS1 in LSCC. The results demonstrated that the expression levels of OIP5-AS1 were significantly increased in LSCC tissues and cell lines. High expression of OIP5-AS1 was closely correlated with lymph node metastasis and advanced clinical stage of LSCC patients. Moreover, in vitro assays showed that OIP5-AS1 overexpression promoted the proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT) of LSCC cells, whereas OIP5-AS1 knockdown exerted suppressive effects on LSCC cells. Furthermore, OIP5-AS1 was confirmed to serve as a competing endogenous RNA of miR-204-5p in LSCC cells, and restoration of miR-204-5p counteracted the OIP5-AS1-mediated oncogenic effects. In conclusion, our study provides promising evidence that lncRNA OIP5-AS1 functions as a tumor promoter in LSCC and may be used as a potential target for LSCC therapy.


Assuntos
Neoplasias Laríngeas/metabolismo , MicroRNAs/metabolismo , Oncogenes , RNA Longo não Codificante/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismo , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Transição Epitelial-Mesenquimal , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/patologia , Metástase Linfática , Masculino , MicroRNAs/genética , Pessoa de Meia-Idade , Invasividade Neoplásica , Estadiamento de Neoplasias , RNA Longo não Codificante/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/secundário , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética
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