Molecular techniques for respiratory diseases: MicroRNA and extracellular vesicles

Gon, Yasuhiro, Tetsuo Shimizu, Kenji Mizumura, Shuichiro Maruoka, and Mari Hikichi. "Molecular techniques for respiratory diseases: MicroRNA and extracellular vesicles." Respirology (2019).

ABSTRACT
miRNA are a class of evolutionarily conserved non‐coding 19‐ to 22‐nt regulatory RNA. They affect various cellular functions through modulating the transcriptional and post‐transcriptional levels of their target mRNA by changing the stability of protein‐coding transcripts or attenuating protein translation. miRNA were discovered in the early 1990s, and they have been the focus of new research in both basic and clinical medical sciences. Today, it has become clear that specific miRNA are linked to the pathogenesis of respiratory diseases, as well as cancer and cardiovascular disease. In addition, EV, including exosomes, which are small membrane‐bound vesicles secreted by cells, were found to contain various functional miRNA that can be used for diagnostic and therapeutic purposes. As body fluids, such as blood and respiratory secretions, are major miRNA sources in the body, EV carrying extracellular miRNA are considered potentially useful for the diagnosis and assessment of pathological conditions, as well as the treatment of respiratory or other diseases. Although research in the field of lung cancer is actively progressing, studies in other respiratory fields have emerged recently as well. In this review, we provide an update in the topics of miRNA and EV focused on airway inflammatory diseases, such as asthma and COPD, and explore their potential for clinical applications on respiratory diseases.

INTRODUCTION
MicroRNA (miRNA) are small nucleic acid molecules that are not directly involved in protein synthesis and are recognized as a distinct class of non‐coding RNA (ncRNA). When they were first discovered in 1993, their biological significance was unknown; however, they were soon found to play an important role in the transmission of genetic information and became a major focus of research.1 The Ambros group from Harvard University first discovered miRNA as a microscopic RNA bound to the mRNA of a nematode; it was found to inhibit the transmission of genetic information.2 In 2000, miRNA were found to exist across a wide range of species. Moreover, it has become evident that their role within these organisms is to attach to intracellularly transcribed mRNA and fine tune gene expression.2, 3

Several miRNA subtypes have been discovered, and each miRNA has been found to suppress the expression of a specific gene. miRNA regulate protein synthesis in several ways, the major ways being mRNA destabilization or translational repression. miRNA and mRNA are not simply bound in a ‘one‐to‐one’ correspondence relationship. In other words, one miRNA may regulate the translation of multiple mRNA. Likewise, the translation of one mRNA may be suppressed by multiple miRNA. In this way, miRNA and mRNA share a ‘many‐to‐many’ relationship. The precise mechanisms underlying miRNA function remain a mystery, but it is estimated that one miRNA targets an average of 200 mRNA. At present, 2588 miRNA have been found in humans, and information on these miRNA can be found in a publicly available database (http://mirbase.org).3 In humans, miRNA are thought to suppress over half of the human genome and be involved in various biological functions from ontogenesis to cell differentiation and proliferation.4

There are several studies about the functions and dynamics of miRNA for their use in clinical settings. Abnormal intracellular miRNA function causes a breakdown in the transmission of genetic information of an organism. As a result, it might induce the capability of sustaining proliferation, growth suppression, cell death, activating migration, enhancing immune response and inducing angiogenesis. Abnormal miRNA expression has been reported to be associated with many diseases, including some cancers.5 Therefore, miRNA are known to play pivotal roles in cancer progression and thought to be promising diagnostic and prognostic biomarkers for cancer.5 As in cancer, clinical research on miRNA expression profile is also expected to contribute to the progression of diagnostic and therapeutics for inflammatory respiratory diseases.

In this review, we summarize the structure, biogenesis, functions and basic experimental methods for exosomes of miRNA and extracellular vesicles (EV) as a cargo of miRNA. In addition, we summarize recent studies on roles of miRNA in the pathogenesis of inflammatory respiratory diseases, such as chronic obstructive pulmonary disease (COPD) and asthma, and explore the possibility for their clinical utility in this field.

View full article