RESUMO
MicroRNAs (miRNAs) are short endogenously expressed RNAs that have the potential to regulate the expression of any RNA. This potential has led to the publication of several thousand papers each year connecting miRNAs to many different genes and human diseases. By contrast, relatively few papers appear that investigate the molecular mechanism used by miRNAs. There is a disconnect between rigorous understanding of mechanism and the extraordinary diversity of reported roles for miRNAs. Consequences of this disconnect include confusion about the assumptions underlying the basic science of human miRNAs and slow development of therapeutics that target miRNAs. Here, we present an overview of investigations into miRNAs and their impact on gene expression. Progress in our understanding of miRNAs would be aided by a greater focus on the mechanism of miRNAs and a higher burden of evidence on researchers who seek to link expression of a particular miRNA to a biological phenotype.
Assuntos
Inativação Gênica , MicroRNAs/genética , Interferência de RNA , Animais , Antagomirs/síntese química , Antagomirs/genética , Antagomirs/uso terapêutico , Pareamento de Bases , Sequência de Bases , Estudos Clínicos como Assunto , Desenvolvimento de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Variação Genética , Humanos , MicroRNAs/síntese química , MicroRNAs/uso terapêutico , Relação Estrutura-Atividade , Resultado do TratamentoRESUMO
Peptide Nucleic Acids (PNAs) are oligonucleotide mimics that can be used to block the biological action of microRNA, thus affecting gene expression post-transcriptionally. PNAs are obtained with solid-phase peptide synthesis, and can be easily conjugated to other peptides. Conjugation with R8-Peptide or modification of the PNA backbone (at C5 or C2 carbon) with arginine side chains allows efficient cellular uptake. The present protocol describes the synthesis of cationic PNAs that can be used alone as drugs or for efficient co-delivery in suitable inorganic nanocarriers.
Assuntos
Antagomirs/síntese química , Oligopeptídeos/química , Ácidos Nucleicos Peptídicos/síntese química , Antagomirs/química , Desenvolvimento de Medicamentos , Humanos , Estrutura Molecular , Nanomedicina , Ácidos Nucleicos Peptídicos/química , Técnicas de Síntese em Fase SólidaRESUMO
Previous studies have suggested that EZH2 is up-regulated in bladder cancer tissues and identified it as a biomarker for poor prognosis. However, the biological functions of EZH2 in bladder cancer cells remain unknown. In this research, we discovered that EZH2 expression is irrelevant to the TNM stage and poor prognosis of bladder cancer patients. But suppression of EZH2 can slowdown the progression of bladder cancer cells. Moreover, we used the technology of synthetic biology to construct the tetracycline-controllable artificial microRNA-HOTAIR + EZH2, which can decrease the expression of HOTAIR and EZH2 in a doxycycline dosage-dependent manner. And we also found that HOTAIR expression was positively correlated with EZH2 expression. Tetracycline-controllable artificial microRNA-HOTAIR + EZH2 can inhibit the proliferation and migration of bladder cancer cells. Meanwhile, the apoptosis rate of bladder cancer cells was increased. Taken together, our research showed the cancer-promoting effects of EZH2 and created a novel method to rescue the development of bladder cancer cells.
Assuntos
Antagomirs/farmacologia , Apoptose/efeitos dos fármacos , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Tetraciclina/farmacologia , Antagomirs/síntese química , Apoptose/genética , Sequência de Bases , Linhagem Celular Tumoral , Movimento Celular , Proliferação de Células , Bases de Dados Factuais , Progressão da Doença , Proteína Potenciadora do Homólogo 2 de Zeste/antagonistas & inibidores , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Humanos , Gradação de Tumores , RNA Longo não Codificante/antagonistas & inibidores , RNA Longo não Codificante/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/terapiaRESUMO
miRNAs are highly conserved class of small ncRNAs whose involvement in human pathophysiologies is extensively investigated. MiR-21 is a well established oncogenic miRNA whose deregulation plays a significant role in onset and progression of cancer. The need of novel approaches to downregulate miR-21 is rapidly expanding. Potent inhibition of miR-21 is achieved by chemically modified 2'-O-methyl RNA oligonucleotide. The serinol capping at 3' and 5'ends and the interspersed 2'-O-(R-2-amino-3-methoxypropyl) uridine units enhance the nuclease resistance and efficacy of 2'-O-methyl RNA for the inhibition of miR-21. This represents a simple and novel modification for developing oligonucleotide-based therapeutics.
