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1.
Sci Rep ; 10(1): 3256, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32094378

RESUMO

Malignant transformation and progression in cancer is associated with the altered expression of multiple miRNAs, which are considered as post-transcriptional regulators of genes participating in various cellular processes. Although, it has been proposed that miR-23b-3p acts as a tumor suppressor in cervical cancer (CC), not all the pathways through which it alters the cellular processes have been described. The present study examines whether miR-23b-3p directly represses the c-Met expression and that consequently modifies the proliferation, migration and invasion of C33A and CaSki cells. c-Met has five microRNA response elements (MREs) for miR-23b-3p in the 3'-UTR region. The ectopic overexpression of miR-23b-3p significantly reduces c-Met expression in C33A and CaSki cells. The overexpression of miR-23b-3p reduces proliferation, migration and invasion of CaSki cells and the proliferation and invasion in C33A cells. In CaSki cells, the activation of Gab1 and Fak, downstream of c-Met, is reduced in response to the overexpression of miR-23b-3p. Together, the results in the present study indicate that miR-23b-3p is a tumor suppressor that modulates the progression of CC via post-transcriptional regulation of the c-Met oncogene.


Assuntos
Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-met/metabolismo , Neoplasias do Colo do Útero/metabolismo , Regiões 3' não Traduzidas , Algoritmos , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Feminino , Humanos , MicroRNAs/metabolismo , Invasividade Neoplásica , Metástase Neoplásica , Elementos de Resposta , Neoplasias do Colo do Útero/patologia
2.
Parasitol Int ; 65(6 Pt A): 625-631, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27620329

RESUMO

Trichomonas vaginalis eIF-5A-like protein (TveIF-5A) belongs to the highly conserved eIF-5A family of proteins that contains a unique polyamine-derived amino acid, hypusine. Recently, we determined that the polyamine putrescine is required for tveif-5a mRNA stability, and it is necessary for stability and maturation of the TveIF-5A protein. Eukaryotic eIF-5A is known to be involved in mRNA turnover and is capable of sequence-specific RNA binding to eIF-5A response elements (EREs). These ERE sequences are present in diverse mammalian mRNAs, including human cyclooxygenase-2 (cox-2). Here, we cloned the complete coding sequence of TveIF-5A and overexpressed it in a eukaryotic system. The recombinant protein (rTveIF-5A) was purified in soluble form using size-exclusion chromatography. Because of the polyamine-dependent regulation of TvCP39 (a protease of T. vaginalis) at the protein and RNA messenger (mRNA) levels, we looked for an ERE-like structure in the 3' region of tvcp39 mRNA. In RNA gel-shift assays, rTveIF-5A bound to transcripts at the EREs of cox-2 or tvcp39 mRNAs. This work shows the eIF-5A/ERE-like interaction in T. vaginalis.


Assuntos
Fatores de Iniciação de Peptídeos/genética , Fatores de Iniciação de Peptídeos/metabolismo , Proteínas de Ligação a RNA/genética , Proteínas de Ligação a RNA/metabolismo , Proteínas Recombinantes/genética , Elementos de Resposta/genética , Trichomonas vaginalis/genética , Animais , Linhagem Celular , Células HeLa , Humanos , Ligação Proteica/genética , Processamento de Proteína Pós-Traducional/genética , RNA Mensageiro/biossíntese , RNA Mensageiro/metabolismo , Proteínas Recombinantes/metabolismo , Fator de Iniciação de Tradução Eucariótico 5A
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