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microRNAs and drug sensitivity in cancer
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Os microRNAs (miRNAs/miRs) são pequenas moléculas de RNA não-codificantes que regulam a expressão génica de uma forma pós-transcricional. Estão envolvidos em diversos processos biológicos como o desenvolvimento, diferenciação, apoptose e proliferação celular. A sua capacidade de interagir com diversos mRNAs dá-lhes um potencial papel terapêutico relevante, extensivamente abordado na actual literatura. Os miRNAs apresentam expressão aberrante no cancro e, recentemente, foram associados também a quimio-resistência em tumores malignos. Esta característica é algo comum, já que a resistência à terapêutica de primeira linha acontece frequentemente. Diversas substâncias activas são utilizadas em quimioterapia e, associadas a elas, podem estar diferentes processos de resistência. Mais recentemente, foram desenvolvidos primórdios de armas terapêuticas com base em miRNAs que conseguem alterar, quer através de mimetização ou de antagonismo, os seus níveis intra-celulares em tecidos-alvo. Estes tornam-se então em potenciais ferramentas para um tratamento conjunto com substâncias quimioterapêuticas alvo de resistências. Para este trabalho, foram selecionados para análise os tumores que maior impacto têm na saúde: mama, próstata, pulmão e colo-rectal. Assim, apresentam-se inúmeros casos em que deficiências ou excessos de miRNAs foram relacionados com resistências específicas e de que forma essas resistências conseguiram ser revertidas com uso a mímicos ou antagonistas de miRNAs.
MicroRNAs (miRNAs/miRs) are short non-coding RNA molecules that regulate gene expression in a post-transcriptional fashion. These are involved in several biological processes such as cellular development, differentiation, apoptosis and proliferation. Their ability to interact with diverse mRNAs confers a potentially relevant therapeutic role, extensively studied in the current literature. miRNAs are aberrantly expressed in cancer, and recently, they were associated to chemoresistance in malignant tumors. This is a common trait since chemoresistance to first line chemotherapy is frequent. Several drugs are used in chemotherapy and diverse resistance processes are associated to them. More recently, primordial therapeutic weapons based on miRNAs have been developed. These tools can alter miRNA intracelular levels in target tissues in vivo, through mimetization or antagonism. These have become potential tools for a combined treatment along with chemotherapeutic drugs subject to resistances. For this work, the most incident and deadly cancer types were selected: breast, prostate, lung and colorectal. Therefore, we present several cases in which downregulation or upregulation of miRNAs were related to specific resistances and in which way they were bypassed or reverted, through the use of miRNA mimics or antagonists.
MicroRNAs (miRNAs/miRs) are short non-coding RNA molecules that regulate gene expression in a post-transcriptional fashion. These are involved in several biological processes such as cellular development, differentiation, apoptosis and proliferation. Their ability to interact with diverse mRNAs confers a potentially relevant therapeutic role, extensively studied in the current literature. miRNAs are aberrantly expressed in cancer, and recently, they were associated to chemoresistance in malignant tumors. This is a common trait since chemoresistance to first line chemotherapy is frequent. Several drugs are used in chemotherapy and diverse resistance processes are associated to them. More recently, primordial therapeutic weapons based on miRNAs have been developed. These tools can alter miRNA intracelular levels in target tissues in vivo, through mimetization or antagonism. These have become potential tools for a combined treatment along with chemotherapeutic drugs subject to resistances. For this work, the most incident and deadly cancer types were selected: breast, prostate, lung and colorectal. Therefore, we present several cases in which downregulation or upregulation of miRNAs were related to specific resistances and in which way they were bypassed or reverted, through the use of miRNA mimics or antagonists.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2014
Palavras-chave
miRNAs Quimioterapia Quimio-resistência anti-Mirs Miméticos Mestrado Integrado - 2014