Unveiling the role of osteoblastic micro RNAs in the skeleton: from biological functions to therapeutic potential / Rol de los micro-ARN osteoblásticos en el esqueleto: desde las funciones biológicas al potencial terapéutico

MicroRNAs (miRNAs) are small non-coding RNA molecules that play critical roles in post-transcriptional gene regulation. They function by binding to target messenger RNA (mRNA) molecules, leading to their degradation or inhibiting their translation into proteins. In the context of skeletal diseases, such as osteoporosis, osteoarthritis, and bone metastasis, there is growing evidence osteoblastic miRNAs, are involved in the regulation of bone formation and maintenance.Osteoblasts are bone-forming cells responsible for synthesizing and depositing the extracellular matrix, which ultimately mineralizes to form bone tissue. Osteoblastic miRNAs modulate various aspects of osteoblast function, including proliferation, differentiation, mineralization, and apoptosis. Dysregulation of these miRNAs can disrupt the balance between bone formation and resorption, leading to skeletal diseases.The therapeutic implications of targeting osteoblastic miRNAs in skeletal diseases are significant. Modulating the expression levels of specific miRNAs holds promise for developing novel therapeutic strategies to enhance bone formation, prevent bone loss, and promote bone regeneration. Potential therapeutic approaches include the use of synthetic miRNA mimics to restore miRNA expression in diseases associated with miRNA downregulation or the use of anti-miRNA oligonucleotides to inhibit miRNA function in diseases associated with miRNA upregulation.miRNA-based therapies are still in the early stages of development, and further research is needed to fully understand the complexity of miRNA networks. Additionally, the delivery of miRNAs to specific target tissues and cells remains a challenge that needs to be addressed for effective clinical translation. Nonetheless, targeting osteoblastic miRNAs represents a promising avenue for future therapeutic interventions in skeletal diseases. (AU)

Los micro-ARNs (miARNss) son pequeños ARN no codificantes que desempeñan un papel fundamental en la regulación génica postranscripcional. Ejercen su función al unir-se a moléculas de ARN mensajero (ARNm), promoviendo su degradación e inhibiendo su traducción en proteínas. En el contexto de las enfermedades esqueléticas, como la osteoporosis, la osteoartritis y la metástasis ósea existe evidencia de que los miARNs osteoblásticos están involucrados en la regulación de la formación y del mantenimiento óseo. Los osteoblastos son células formadoras de hueso responsables de sintetizar y depositar la matriz extracelular, que finalmente se mineraliza para formar el hueso. Los miARNs derivados de osteoblastos modulan varios aspectos de la función de estas células, incluida la proliferación, diferenciación, mineralización y la apoptosis. La desregulación de estos miARNs puede alterar el equilibrio entre la formación y la resorción ósea, lo que lleva a enfermedades óseas. Las implicaciones terapéuticas de los miARNs osteoblásticos en enfermedades esqueléticas son significativas. La modulación de los niveles de expresión de miARNs específicos es prometedora para desarrollar nuevas estrate-gias terapéuticas a fin de mejorar la formación, prevenir la pérdida y promover la regeneración ósea. Los enfoques terapéuticos potenciales incluyen el uso de miméticos de miARNs para restaurar la expresión de miARNs o el uso de oligonucleótidos anti-miARNs para inhibir su función. Las terapias basadas en miARNs aún se encuentran en las primeras etapas de desarrollo. La administración de miARNs a las células y los tejidos específicos sigue siendo un desafío para lograr una aplicación clínica eficaz. (AU)

MicroRNAs, cancer and ionizing radiation: Where are we? / MicroRNAs, câncer e radiação ionizante: em que ponto estamos?

Summary The aim of this study is to describe the biogenesis of microRNA, its relations with carcinogenesis, and the correlation between microRNA and ionizing radiation (IR), focusing on radioresponsiveness. It is known that microRNA biogenesis is well established and involves different enzymatic cleavages, resulting in the production of mature microRNA. MicroRNAs are involved in carcinogenesis. Their interaction is related to the genetic and epigenetic changes associated with activation of proto-oncogenes or inactivation of tumor suppressor genes. Several studies have shown that the levels of expression of some microRNAs vary significantly after irradiation. There are evidences that microRNAs can influence cellular response after IR. In addition, microRNAs are related to modulation of the expression of several post-transcriptional targets in DNA damage response pathways, and to the DNA damage repair regulation mechanism. Future studies can clarify a possible clinical use of microRNAs as a new class of radiosensitive agents.

Resumo O objetivo do presente estudo é descrever a biogênese do microRNA, suas relações na carcinogênese e a correlação do microRNA com a radiação ionizante (RI), com enfoque na radiorresponsividade. Observou-se que a biogênese do microRNA está bem estabelecida e envolve diversas clivagens enzimáticas que resultam na produção do microRNA maduro. Os microRNAs estão envolvidos na carcinogênese. Sua interação está relacionada às alterações genéticas e epigenéticas, associadas à ativação de proto- -oncogenes ou à inativação de genes supressores de tumor. Vários estudos demonstraram que os níveis de expressão de alguns microRNAs variam significativamente após a irradiação. Há evidências de que os microRNAs podem influenciar a resposta celular após a RI. Além disso, os microRNAs estão relacionados à modulação da expressão de vários alvos de pós-transcrição das vias de resposta aos danos no DNA e o do mecanismo de regulação de reparação de danos do DNA. Estudos futuros podem elucidar uma possível utilização clínica dos microRNAs como uma nova classe de agentes radiossensíveis.

Expression and role of miR-34a in bladder cancer.

To investigate the biological function of microRNA-34a (miR-34a) in bladder cancer, the expression of miR-34a was determined using quantitative real-time polymerase chain (qRT-PCR) reaction in 42 cases of bladder cancer. The relationship between the expression of miR-34a and development of bladder cancer was also studied. The mature mimics of miR-34a were chemically synthesized and transiently transfected into human bladder cancer T24 cells. The effects of miR-34a on apoptosis, cell cycle and proliferation in T24 cells were evaluated by flow cytometry and MTT, respectively. The results showed that the low expression rate of miR-34a was correlated with the malignancy and tumor size of bladder cancer. The up-regulation of miR-34a in T24 cells contributed to cell growth and cell cycle arrest, but not caspase-3 pathway. These findings suggest that the relative low expression of miRNA-34a might be involved in the tumorigenesis of bladder cancer.