Análise celular e molecular do miRNA-149-3p no processo de migração e adesão em células de carcinoma hepatocelular e sua correlação com o metabolismo de lipídeos
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2019-02-22
Autores
Morais, Priscila Ferrari de
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Universidade Estadual Paulista (Unesp)
Resumo
O carcinoma hepatocelular (CHC) ocupa o 5º lugar entre os cânceres mais comum no mundo. No geral, cânceres apresentam alto risco de recorrência na forma de doença metastática. A identificação e caracterização funcional de genes associados à invasão e metástase é crucial para o desenvolvimento de novas terapias orientada contra esse processo. A proteína celular associada a migração e angiogênese (AAMP), está amplamente distribuída em muitos tipos de células com potencial migratório. Associado a isso, vários estudos apontam o papel crucial do metabolismo lipídico na iniciação das metástases. Estudos demonstram que os microRNAs (miRNAs) têm um papel central no controle das funções básicas das células. Um miRNA de grande interesse para este trabalho é o miRNA-149-3p. Em trabalhos realizados anteriormente pelo grupo de pesquisa, foi demonstrado que em células tumorais pulmonares (A549) esse miRNA foi apontado como um elemento de destaque no controle dos processos celulares de migração, pelo controle da proteína celular associada a migração e angiogênese (AAMP). Tendo em vista as doenças hepáticas, cabe avaliar os efeitos do miRNA-149-3p, considerando a existência de alvos putativos a esse miRNA, que se correlacionam diretamente com o metabolismo energético, buscando analisar pontos da via onde ocorre modulação ocasionada por este miRNA. Para as análises optou-se por trabalhar com as células SK-HEP-1 (linhagem metastática) e HEP-G2 (linhagem metabolizadora). Segundo as análises, demonstrou-se que tanto para SK-HEP-1 quanto para HEP-G2 a AAMP não é a proteína principal, responsável pelo controle da migração. Ao analisar a expressão dos genes correlatos ao processo de migração e adesão celular (MMP2 e MMP9; TIMP1 e TIMP2; Ocludina, TJP1 entre outros), observa-se que em SK-HEP-1 apresenta, aumento desses genes ao transfectar as células com o miR-149-3p mímico; e também houve aumento na expressão dos fatores de transcrição envolvidos no metabolismo de lipídeos, inferindo que este microRNA potencializa e garante energia para as células desempenharem suas atividades (promove migração). Diferentemente em HEP-G2, onde os genes correlatos ao processo de migração e adesão aumentam ao inibir o miR-149-3p, que também, mostrou-se um modelo interessante no estudo do metabolismo energético. No presente estudo, o miR-149-3p obteve maior relevância no controle do metabolismo de lipídeos. A importância desse trabalho se destaca, uma vez que, o tratamento clínico com microRNAs ainda precisa de muita atenção, dedicação e pesquisa.
Hepatocellular carcinoma (CHC) ranks 5th among the most common cancers in the world. In general, cancers are at high risk of recurrence in the form of metastatic disease. The identification and functional characterization of genes associated with invasion and metastasis is crucial for the development of new therapies targeted against this process. Cellular protein associated with migration and angiogenesis (AAMP), is widely distributed in many cell types with migratory potential. Associated with this, several studies point to the crucial role of lipid metabolism in the initiation of metastases. Studies have shown that microRNAs (miRNAs) play a central role in the control of basic cell functions. A miRNA of great interest for this work is miRNA-149-3p. In previous studies by the research group, it was demonstrated that in lung tumor cells (A549) this miRNA was indicated as a prominent element in the control of cellular migration processes, by the cellular protein control associated with migration and angiogenesis (AAMP). Considering the hepatic diseases, the effects of miRNA-149-3p can be evaluated, considering the existence of putative targets for this miRNA, which correlate directly with the energetic metabolism, seeking to analyze points of the pathway where the miRNA modulation occurs. For the analyzes we opted to work with the SK-HEP-1 (metastatic line) and HEP-G2 (metabolizing line) cells. According to the analyzes, it has been shown that for both SK-HEP-1 and HEP-G2 the AAMP is not the main protein responsible for migration control. In analyzing the expression of the genes correlated to the process of migration and cell adhesion (MMP2 and MMP9, TIMP1 and TIMP2, Occludin, TJP1 among others), it is observed that in SK-HEP-1 it presents, increase of these genes when transfecting cells with or miR-149-3p mimic; and there was also an increase in the expression of the transcription factors involved in lipid metabolism, inferring that this microRNA potentiates and guarantees energy for cells to perform their activities (promotes migration). Differently in HEP-G2, where the genes correlated to the migration and adhesion process increase when inhibiting miR-149-3p, which also proved to be an interesting model in the study of energy metabolism. In the present study, miR-149-3p was more relevant in the control of lipid metabolism. The importance of this work stands out, since, the clinical treatment with microRNAs still needs a lot of attention, dedication and research.
Hepatocellular carcinoma (CHC) ranks 5th among the most common cancers in the world. In general, cancers are at high risk of recurrence in the form of metastatic disease. The identification and functional characterization of genes associated with invasion and metastasis is crucial for the development of new therapies targeted against this process. Cellular protein associated with migration and angiogenesis (AAMP), is widely distributed in many cell types with migratory potential. Associated with this, several studies point to the crucial role of lipid metabolism in the initiation of metastases. Studies have shown that microRNAs (miRNAs) play a central role in the control of basic cell functions. A miRNA of great interest for this work is miRNA-149-3p. In previous studies by the research group, it was demonstrated that in lung tumor cells (A549) this miRNA was indicated as a prominent element in the control of cellular migration processes, by the cellular protein control associated with migration and angiogenesis (AAMP). Considering the hepatic diseases, the effects of miRNA-149-3p can be evaluated, considering the existence of putative targets for this miRNA, which correlate directly with the energetic metabolism, seeking to analyze points of the pathway where the miRNA modulation occurs. For the analyzes we opted to work with the SK-HEP-1 (metastatic line) and HEP-G2 (metabolizing line) cells. According to the analyzes, it has been shown that for both SK-HEP-1 and HEP-G2 the AAMP is not the main protein responsible for migration control. In analyzing the expression of the genes correlated to the process of migration and cell adhesion (MMP2 and MMP9, TIMP1 and TIMP2, Occludin, TJP1 among others), it is observed that in SK-HEP-1 it presents, increase of these genes when transfecting cells with or miR-149-3p mimic; and there was also an increase in the expression of the transcription factors involved in lipid metabolism, inferring that this microRNA potentiates and guarantees energy for cells to perform their activities (promotes migration). Differently in HEP-G2, where the genes correlated to the migration and adhesion process increase when inhibiting miR-149-3p, which also proved to be an interesting model in the study of energy metabolism. In the present study, miR-149-3p was more relevant in the control of lipid metabolism. The importance of this work stands out, since, the clinical treatment with microRNAs still needs a lot of attention, dedication and research.
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Palavras-chave
Câncer de fígado CHC, MicroRNAs, Metabolismo de lipídeos, Migração celular, Cultura de células, Liver cancer HCC, Lipid metabolism, Cell migration, Cell culture