Advances in the Regulation of Follicular Development by Extracellular Vesicles and Non-Coding RNAs / 中国医学科学院学报

Extracellular vesicles (EV),nanoscale vesicles encapsulated by phospholipid bilayers,are rich in biological molecules such as nucleic acids,metabolites,proteins,and lipids derived from parental cells.They are mainly involved in intercellular communication,signal transmission,and material transport and affect the functions of target cells.Ovulation disorders account for a higher proportion in the factors causing infertility which demonstrates increasing incidence year by year.Non-coding RNAs participate in a series of physiological and pathological processes of follicular development,playing a key role in female infertility.This review systematically introduces the types and biological roles of EV and elaborates on the regulation of follicular development from the effects of EV and non-coding RNAs on granulosa cell function,oocyte maturation,ovulation,luteal formation,and steroid hormone synthesis,providing a new idea and a breakthrough point for the diagnosis and treatment of infertility.

Non-coding RNAs: a promising target for early metastasis intervention / 中华医学杂志(英文版)

Metastases account for the overwhelming majority of cancer-associated deaths. The dissemination of cancer cells from the primary tumor to distant organs involves a complex process known as the invasion-metastasis cascade. The underlying biological mechanisms of metastasis, however, remain largely elusive. Recently, the discovery and characterization of non-coding RNAs (ncRNAs) have revealed the diversity of their regulatory roles, especially as key contributors throughout the metastatic cascade. Here, we review recent progress in how three major types of ncRNAs (microRNAs, long non-coding RNAs, and circular RNAs) are involved in the multistep procedure of metastasis. We further examine interactions among the three ncRNAs as well as current progress in their regulatory mechanisms. We also propose the prevention of metastasis in the early stages of cancer progression and discuss current translational studies using ncRNAs as targets for metastasis diagnosis and treatments. These studies provide insights into developing more effective strategies to target metastatic relapse.

Roles of exosome-derived non-coding RNA in tumor micro-environment and its clinical application / 浙江大学学报·医学版

Tumor-derived exosomes play an important role in the tumor micro-environment. The exosome-derived non-coding RNAs are transmitted in the tumor microenvironment in three ways, communication between tumor cells, normal cells affecting tumor cells, and tumor cells affecting normal cells. Through these three ways, exosomal non-coding RNAs are involved in the regulation of tumor progression, affecting tumor angiogenesis, tumor invasiveness, drug resistance, stemness, tumor metabolic repro-gramming and immune escape, resulting in dual roles in promoting or inhibiting tumor development. Exosomes have a membranous structure and their contents are resistant to degradation by extracellular proteases and remain highly stable in body fluids, thus exosome-derived non-coding RNAs are expected to serve as diagnostic and prognostic indicators for a variety of cancers. In addition, exosomes can be used to deliver non-coding RNAs for targeted therapy, or to knock down or modify tumor-promoting non-coding RNAs for tumor therapy. This article reviews the function and communication mechanism of exosomal non-coding RNAs in the tumor microenvironment, including their pathways of action, effects, potential values for tumor biomarkers and treatment targets. This article also points out the issues that need to be further studied in order to promote the progress of extracellular non-coding RNAs in cancer research and their application in tumor diagnosis and treatment.

Regulation of non-coding RNA in type H vessels angiogenesis of bone / 中国修复重建外科杂志

OBJECTIVE@#To summarize the regulatory effect of non-coding RNA (ncRNA) on type H vessels angiogenesis of bone.@*METHODS@#Recent domestic and foreign related literature about the regulation of ncRNA in type H vessels angiogenesis was widely reviewed and summarized.@*RESULTS@#Type H vessels is a special subtype of bone vessels with the ability to couple bone formation. At present, the research on ncRNA regulating type H vessels angiogenesis in bone diseases mainly focuses on microRNA, long ncRNA, and small interfering RNA, which can affect the expressions of hypoxia inducible factor 1α, platelet derived growth factor BB, slit guidance ligand 3, and other factors through their own unique ways of action, thus regulating type H vessels angiogenesis and participating in the occurrence and development of bone diseases.@*CONCLUSION@#At present, the mechanism of ncRNA regulating bone type H vessels angiogenesis has been preliminarily explored. With the deepening of research, ncRNA is expected to be a new target for the diagnosis and treatment of vascular related bone diseases.

Promising roles of non-exosomal and exosomal non-coding RNAs in the regulatory mechanism and as diagnostic biomarkers in myocardial infarction / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Non-exosomal non-coding RNAs (non-exo-ncRNAs) and exosomal ncRNAs (exo-ncRNAs) have been associated with the pathological development of myocardial infarction (MI). Accordingly, this analytical review provides an overview of current MI studies on the role of plasma non-exo/exo-ncRNAs. We summarize the features and crucial roles of ncRNAs and reveal their novel biological correlations via bioinformatics analysis. The following contributions are made: (1) we comprehensively describe the expression profile, competing endogenous RNA (ceRNA) network, and "pre-necrotic" biomarkers of non-exo/exo-ncRNAs for MI; (2) functional enrichment analysis indicates that the target genes of ncRNAs are enriched in the regulation of apoptotic signaling pathway and cellular response to chemical stress, etc.; (3) we propose an updated and comprehensive view on the mechanisms, pathophysiology, and biomarker roles of non-exo/exo-ncRNAs in MI, thereby providing a theoretical basis for the clinical management of MI.

Regulation of Glial Function by Noncoding RNA in Central Nervous System Disease / 神经科学通报·英文版

Non-coding RNAs (ncRNAs) are a class of functional RNAs that play critical roles in different diseases. NcRNAs include microRNAs, long ncRNAs, and circular RNAs. They are highly expressed in the brain and are involved in the regulation of physiological and pathophysiological processes of central nervous system (CNS) diseases. Mounting evidence indicates that ncRNAs play key roles in CNS diseases. Further elucidating the mechanisms of ncRNA underlying the process of regulating glial function that may lead to the identification of novel therapeutic targets for CNS diseases.

Research advances on the mechanism of non-coding RNA regulated diabetic wound healing / 中华烧伤杂志

Diabetic wounds are a common complication of diabetic patients, and the incidence has been increasing in recent years. In addition, its poor clinical prognosis seriously affects the quality of life of patients, which has become the focus and difficulty of diabetes treatment. As the RNA regulating gene expression, non-coding RNA can regulate the pathophysiological process of diseases, and play an important role in the healing process of diabetic wounds. In this paper, we reviewed the regulatory role, diagnostic value, and therapeutic potential of three common non-coding RNA in diabetic wounds, in order to provide a new solution for the diagnosis and treatment of diabetic wounds at the genetic and molecular level.

Papel de los exosomas en la angiogénesis, revascularización y respuesta inmune / Role of exosomes in angiogenesis, revascularization and immune response

Introducción: Los exosomas son vesículas extracelulares de tamaño nanométrico, que se generan cuando los endosomas multivesiculares se fusionan con la membrana plasmática y el contenido de las vesículas intraluminales se libera en el espacio extracelular. Son producidos por casi todos los tipos de células, en condiciones fisiológicas y patológicas. Transportan proteínas, lípidos y ácido ribonucleico (ARN) no codificante, desde la célula madre hasta la célula receptora, estos son considerados un punto clave en la regeneración de tejidos, lo que se ha demostrado en una serie de estudios, con diferentes tejidos corporales, como piel, cartílago, pancreático y tejidos cardiovasculares. Objetivo: Explicar los aspectos generales y posibles usos de los exosomas en el campo médico. Métodos: Se realizó una búsqueda de información mediante consulta en las bases de datos SciELO PubMed, Science Direct y Lilacs, en los idiomas español e inglés, con diferentes combinaciones de palabras claves y términos MESH como: exosomes, neovascularization, wound healing, immunity, micro RNA, immunology, therapy, classification. Se efectuó un análisis y resumen de la información revisada. Conclusiones: En la actualidad, los exosomas se han convertido en objeto de investigación para diversos tratamientos, medicamentos y uso como marcadores moleculares. Se destacan en terapias contra el cáncer, la inmunomodulación, la estimulación o supresión de la angiogénesis, regeneración cutánea, cicatrización y curación de heridas; por lo que de forma general resultan prometedores en el ámbito de las ciencias médicas(AU)

Introduction: Exosomes are nano-sized extracellular vesicles, which are generated when multivesicular endosomes fuse with the plasma membrane and the content of intraluminal vesicles released into the extracellular space. Are produced by almost all types of cells, under physiological and pathological conditions and they transport proteins, lipids and non-coding RNA (ribonucleic acid), from the stem cell to the recipient cell, these are considered a key point in tissue regeneration, which has been shown in a series of studies, with different body tissues, such as skin, cartilage, pancreatic and cardiovascular tissues. Objective: To explain the general aspects and possible uses of exosomes in the medical field. Methods: A search for information was carried out by consulting the Scielo, PubMed, ScienceDirect and Lilacs databases, in Spanish and English, with different combinations of keywords and MESH terms such as: exosomes, neovascularization, wound healing, immunity, microRNA, immunology, therapy, classification. Then, an analysis and summary of the reviewed information was carried out. Conclusions: Currently, exosomes have become the object of research for various treatments, drugs, and their use as molecular markers. They stand out in cancer therapies, immunomodulation, stimulation or suppression of angiogenesis, skin regeneration, and wound healing, which is why they are generally promising in the field of medical sciences(AU)

Role and mechanism of non-coding RNA in the pathogenesis of acute kidney injury / 生理学报

Acute kidney injury (AKI) is a common clinical syndrome and an independent risk factor of chronic kidney disease and end-stage renal failure. At present, the treatments of AKI are still very limited and the morbidity and mortality of AKI are rising. Non-coding RNAs (ncRNAs), including microRNAs, long non-coding RNAs and circular RNAs (circRNAs), are RNAs that are transcribed from the genome, but not translated into proteins. It has been widely reported that ncRNA is involved in AKI caused by ischemia reperfusion injury (IRI), drugs and sepsis through different molecular biological mechanisms, such as apoptosis and oxidative stress response. Therefore, ncRNAs are expected to become a new target for clinical prevention and treatment of AKI and a new biomarker for early warning of the occurrence and prognosis of AKI. Here, the role and mechanism of ncRNA in AKI and the research progress of ncRNA as biomarkers are reviewed.

Research Progress of Non-coding RNA in Multiple Myeloma with Heart Disease---Review / 中国实验血液学杂志

Some non-coding RNAs (ncRNA), as functional RNA molecules, lack potential to encode proteins, but can affect gene expression and disease progression through a variety of mechanisms. In multiple myeloma (MM), cardiovascular disease is one of the most common complications, which may be related to a variety of factors, including patient's own factors, disease-related factors, drug factors, etc. Non-coding RNA is considered to be an important regulator of cardiovascular event risk factors and cell function, and an important candidate target for improving the condition and prognostic assessment. This article briefly summarized the role of non-coding RNA in cardiac amyloidosis caused by MM, damage to the heart by inflammatory factors, and heart disease caused by chemotherapy drugs in recent years.

Effect of exosome / 中南大学学报(医学版)

Traumatic brain injury (TBI) is a main cause of death and disability worldwide, posing a serious threat to public health. But currently, the diagnosis and treatments for TBI are still very limited. Exosomes are a group of extracellular vesicles and participate in multiple physiological processes including intercellular communication and substance transport. Non-coding RNAs (ncRNA) are of great abundancy as cargo of exosomes. Previous studies have shown that ncRNAs are involved in several pathophysiological processes of TBI. However, the concrete mechanisms involved in the effects induced by exosome-derived ncRNA remain largely unknown. As an important component of exosomes, ncRNA is of great significance for diagnosis, precise treatment, response evaluation, prognosis prediction, and complication management after TBI.

Select Macrophage Noncoding RNAs of Interest in Cardiovascular Disease

Cardiovascular disease remains a leading cause of morbidity and mortality worldwide. Aspects of disease severity that are associated with heightened inflammation, such as during atherosclerosis or after myocardial infarction, are correlated with macrophage activation and macrophage polarization of the transcriptome and secretome. In this setting, non-coding RNAs (ncRNAs) may be as abundant as protein-coding genes and are increasingly recognized as significant modulators of macrophage gene expression and cytokine secretion, although the functions of most ncRNAs—and in particular, long non-coding RNAs—remain unknown. Herein, we discuss a subset of specific ncRNAs of interest in macrophages in atherosclerosis and during myocardial inflammation.

Research progress of non-coding RNA in regulating the function of T cells in asthma / 生理学报

Bronchial asthma (i.e. asthma) is a chronic inflammatory disease characterized by airway inflammatory response, hyperresponsiveness and airway remodeling, in which T cells play a vital role, especially T helper cells (Th cells). Non-coding RNAs (ncRNAs) are the RNAs that do not encode proteins, mainly including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), which are widely found in eukaryotic genomes and participate in the regulation of various biological processes. Previous studies have shown that ncRNAs play an important role in the activation and transformation of T cells and other biological processes in asthma. The specific molecular mechanism and clinical application are worth in-depth discussion. This article reviewed the research progress in regulation of miRNAs, lncRNAs and circRNAs on T cells in asthma in recent years.

Research Progress of Non-coding RNA and Endometrial Receptivity / 中国医学科学院学报

Endometrial receptivity has become the main cause of fertilization and pregnancy outcomes in infertile patients,bringing large psychological damage and economic loss to the patients and their family. In recent years,the role of non-coding RNA has increasingly been recognized. The relationship between non-coding RNA and endometrial receptivity is reviewed in this article.

Research Progress on Estimation of Postmortem Interval Using mRNA and ncRNA / 法医学杂志

Postmortem interval （PMI） estimation has always been an important and difficult issue in the field of forensic pathology. In recent years, research progress on the estimation of PMI using RNA specific variation patterns after death has been made by researchers at home and aboard. This paper summarizes the specific application methods of messenger RNA and non-coding RNA for PMI estimation based on the literatures and discusses the existing problems and development trends, in order to provide technical reference for related studies and estimation practice.

The Roles of miRNAs in Medulloblastoma: A Systematic Review

Medulloblastoma is considered one of the most threatening malignant brain tumors with an extremely high mortality rate in children. In the medulloblastoma, there are several genes and mutations found to work in an unregulated manner that works together to push the cells into a cancerous state. With the discovery of non-coding RNAs such as microRNAs (miRNAs), it has been shown that a different layer of gene regulations may be disrupted which would cause cancer. This fact led scientists to put their focus on the role of miRNAs in cancer. A mature miRNA contains a seed sequence which gives the miRNA to identify and attach to the interest mRNA; this attachment may lead degradation of mRNA or suppress of translation of the mRNA. The expression of miRNAs in medulloblastoma shows that some of these non-coding RNAs are overexpressed (OncomiRs) which help cells to proliferate and keep their stemness features. On the other hand, there are other forms of these miRNAs which normally inhibit cell proliferation and promote cell differentiation (tumor suppressor). These are down-regulated during cancer progression. In this systematic review, we attempted to gather several important studies on miRNAs’ role in medulloblastoma tumors and the importance of these non-coding RNAs in the future study of cancer.

Silencing of LncRNA-ANCR Promotes the Osteogenesis of Osteoblast Cells in Postmenopausal Osteoporosis via Targeting EZH2 and RUNX2

PURPOSE: This study aimed to explore the effects and mechanisms of long non-coding RNA (lncRNA) anti-differentiation non-coding RNA (ANCR) on the osteogenesis of osteoblast cells in postmenopausal osteoporosis (PMOP). MATERIALS AND METHODS: Mice models of PMOP were established. ANCR expression and intracellular calcium ions were detected by quantitative real-time polymerase chain reaction (qRT-PCR) and laser confocal microscopy, respectively. ANCR was silenced in osteoblast cells from PMOP mice by the transfection of siRNA-ANCR (si-ANCR). The proliferation and apoptosis of osteoblast cells was analyzed by MTT and flow cytometry, respectively. Alkaline phosphatase (ALP) activity and calcium nodules were examined by ALP and alizarin red staining assay, respectively. The expression of enhancer of zeste homolog 2 (EZH2), runt related transcription factor 2 (RUNX2), and OSTERIX was detected by qRT-PCR and Western blot. Furthermore, an osteogenesis model was constructed in mice, and osteoid formation was observed by hematoxylin-eosin (HE) staining. The interaction between lncRNA-ANCR and EZH2 was further identified by RNA pull-down assay. RESULTS: ANCR expression and intracellular calcium ions were increased in PMOP mice. Si-ANCR significantly increased the proliferation, ALP activity, calcium deposition of osteoblast cells and decreased apoptosis. ANCR and EZH2 were down-regulated by si-ANCR, while RUNX2 and OSTERIX were upregulated. Si-ANCR also promoted osteoid formation in mice treated with hydroxyapatite-tricalcium phosphate. In addition, ANCR specifically bound to EZH2. CONCLUSION: Silencing ANCR promotes the osteogenesis of PMOP osteoblast cells. The specific binding of ANCR with EZH2 suppressed RUNX2, thereby inhibiting osteogenesis.

Exosomes as Therapeutic Vehicles for Cancer

BACKGROUND: Exosomes are membrane-enclosed extracellular vesicles implicated in cell-cell communication. Exosomes contain proteins, mRNAs, non-coding RNAs (miRNAs and lncRNAs) and lipids that are derived from producing cells. These nano-sized vesicles are present in biofluids including blood, urine, saliva, amniotic fluid, semen and conditioned media of cultured cells. METHODS: This review summarizes current progress on the strategies of development of diagnostic biomarkers and drug loading onto exosomes for overcoming cancer progression. RESULTS: A number of studies indicate that the exosome appears to be a key player in tissue repair and regeneration of in a number of animal disease models. In addition, alterations of the molecular profiles in exosomes are known to be correlated with the disease progression including cancer, suggesting their usefulness in disease diagnosis and prognosis. Studies utilizing engineered exosomes either by chemical or biological methods have demonstrated promising results in a number of animal models with cancer. CONCLUSION: Understanding the molecular and cellular properties of exosomes offer benefits for cancer diagnosis by liquid biopsy and for their application in therapeutic drug delivery systems. Studies have shown that genetic or molecular engineering of exosomes augmented their target specificity and anticancer activity with less toxicity. Thus, deeper understanding of exosome biology will facilitate their therapeutic potential as an innovative drug delivery system for cancer.

Long non-coding RNA T-cell leukemia/lymphoma 6 serves as a sponge for miR-21 modulating the cell proliferation of retinoblastoma through PTEN

Retinoblastoma (Rb) is one of the most common eye malignancies occur in childhood. The crucial roles of non-coding RNAs, particularly long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been widely reported in Rb progression. In the present study, we found the expression of lncRNA T-cell leukemia/lymphoma 6 (TCL6) was significantly downregulated in Rb tissues and cell lines. Knockdown of lncRNA TCL6 promoted cell proliferation while reduced cell apoptosis in Rb cells. Moreover, lncRNA TCL6 serves as a sponge for miR-21, a previously-reported oncogenic miRNA in Rb, by direct targeting to negatively regulated miR-21 expression, therefore modulating Rb proliferation through miR-21. TCL6 overexpression inhibited Rb cell proliferation while miR-21 overexpression exerted an opposing effect; the effect of TCL6 overexpression was partially attenuated by miR-21 overexpression. PTEN/PI3K/AKT signaling pathway was involved in lncRNA TCL6/miR-21 axis modulating Rb cell proliferation. Taken together, lncRNA TCL6 serves as a tumor suppressor by acting as a sponge for miR-21 to counteract miR-21-mediated PTEN repression.

Alternative role of noncoding RNAs: coding and noncoding properties / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Noncoding RNAs (ncRNAs) have played a critical role in cellular biological functions. Recently, some peptides or proteins originating from annotated ncRNAs were identified in organism development and various diseases. Here, we briefly review several novel peptides translated by annotated ncRNAs and related key functions. In addition, we summarize the potential mechanism of bifunctional ncRNAs and propose a specific "switch" triggering the transformation from the noncoding to the coding state under certain stimuli or cellular stress. The coding properties of ncRNAs and their peptide products may provide a novel horizon in proteomic research and can be regarded as a potential therapeutic target for the treatment of various diseases.