Small Molecular RNA Research Articles

Role of miRNA-21 in radiation-induced heart disease

Abstract Radiation-induced heart disease (RIHD) is a potentially fatal clinical complication of chest radiotherapy (RT). RIHD is detrimental to the long-term health of post-RT survivors and limits the dose and intensity of RT required to effectively kill tumor cells. However, the cellular and molecular mechanisms underlying these effects remain largely unknown. MicroRNAs (miRNAs) are highly conserved, non-coding, single-stranded, small molecular RNAs that regulate gene expression and participate in cellular proliferation, apoptosis, differentiation, and disease development. MicroRNA-21 (miRNA-21) has become one of the most intensively studied miRNAs in the fields of cancer and cardiovascular disease in recent years. miRNA-21 plays an important role in RIHD progression. This article reviews the origin and function of miRNA-21 in the cardiovascular system and its role in RIHD pathogenesis. In addition, the potential role of miRNA-21 as a new target for predicting and treating RIHD is also discussed.

Tetrahedral Framework Nucleic Acid Delivered RNA Therapeutics Significantly Attenuate Pancreatic Cancer Progression via Inhibition of CTR1-Dependent Copper Absorption.

Copper is vital for various life processes, whereas severely toxic at excess level. Intracellular copper homeostasis is strictly controlled by a set of transporters and chaperones encoded by the copper homeostasis genes. Increasing evidence has shown that copper is usually overloaded in multiple malignancies, including pancreatic cancer, which has an extremely poor prognosis. Recently, silencing the SLC31A1 gene, which encodes a major transmembrane copper transporter (CTR1), has been demonstrated to be an effective means for reducing the malignant degree of pancreatic cancer by downregulating the cellular copper levels. Herein, we utilized tetrahedral framework nucleic acids (tFNAs) as vehicles to overcome the biological barriers for delivering small molecular RNAs and efficiently transferred two kinds of CTR1 mRNA-targeted RNA therapeutics, siCTR1 or miR-124, into PANC-1 cells. Both therapeutic tFNAs, termed t-siCTR1 and t-miR-124, prevented copper intake more effective than the free RNA therapeutics via efficiently suppressing the expression of CTR1, thereby significantly attenuating the progression of PANC-1 cells. In this study, therapeutic tFNAs are constructed to target metal ion transporters for the first time, which may provide an effective strategy for future treatment of other metal metabolism disorders.

MicroRNAs, the Link Between Dengue Virus and the Host Genome.

Dengue virus (DENV) is a small envelope virus of Flaviviridae that is mainly transmitted by Aedes aegypti and Aedes albopictus. It can cause dengue fever with mild clinical symptoms or even life-threatening dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). At present, there are no specific drugs or mature vaccine products to treat DENV. microRNAs (miRNAs) are a class of important non-coding small molecular RNAs that regulate gene expression at the post-transcriptional level. It is involved in and regulates a series of important life processes, such as growth and development, cell differentiation, cell apoptosis, anti-virus, and anti-tumor. miRNAs also play important roles in interactions between host and viral genome transcriptomes. Host miRNAs can directly target the genome of the virus or regulate host factors to promote or inhibit virus replication. Understanding the expression and function of miRNAs during infection with DENV and the related signal molecules of the miRNA-mediated regulatory network will provide new insights for the development of miRNA-based therapies.

Cyclic cis-1,3-Diamines Derived from Bicyclic Hydrazines: Synthesis and Applications

AbstractCyclic cis-1,3-diamines are versatile building blocks frequently found in natural molecules or biologically active compounds. In comparison with widely studied 1,2-diamines, and despite their chemical similarity, 1,3-diamines have been investigated less intensively probably because of a lack of general synthetic procedures giving access to these compounds with good levels of chemo-, regio-, and stereocontrol. In this Account we will give a general overview of the biological interest of cyclic cis-1,3-diamines. We will then describe the synthesis and potential applications of these compounds with a particular focus on the work realized in our laboratory.1 Introduction2 Biological Relevance of the cis-1,3-Diamine Motif3 Classical Synthetic Strategies towards cis-1,3-Diamines4 N–N Bond Cleavage of Bicyclic Hydrazines: A Versatile Method to Access cis-1,3-Diamines4.1 Preparation of Five-Membered Cyclic cis-1,3-Diamino Alcohols4.2 Access to Fluorinated 1,3-cis-Diaminocyclopentanes4.3 Synthesis of cis-1,3-Diaminocyclohexitols4.4 Formation of Cyclic cis-3,5-Diaminopiperidines5 Applications of Cyclic cis-1,3-Diamines5.1 Small-Molecular RNA Binders5.2 Fluorinated 1,3-Diamino Cyclopentanes as NMR Probes6 Concluding Remarks

Hsa-miR-889-3p promotes the proliferation of osteosarcoma through inhibiting myeloid cell nuclear differentiation antigen expression

Osteosarcoma accounts for about 0.2% in human malignant solid tumors. The mortality and metastatic rates of osteosarcoma remain relatively high. MicroRNA (miRNA) is a kind of non-coding small-molecular RNA discovered in recent years. Various studies have identified the involvement of miRNA in the occurrence and development of tumor as an oncogene or tumor-suppressor gene. This study aims to investigate the effect of hsa-miR-889-3p on the progression of osteosarcoma and its underlying mechanism. Through the bioinformatics methods, we first found that hsa-miR-889-3p was upregulated in osteosarcoma, and it was a prognostic risk factor for osteosarcoma. Additionally, the gene set enrichment analysis (GSEA) revealed that hsa-miR-889-3p mainly affected cell cycle progression and proliferation of osteosarcoma. To verify the bioinformatics results, regulatory effects of hsa-miR-889-3p on osteosarcoma both in vitro and in vivo experiments were investigated. It is found that hsa-miR-889-3p could promote the proliferation of osteosarcoma cells though regulating cell cycle progression. Tumor size and growth rate of osteosarcoma were influenced by hsa-miR-889-3p in xenograft models. To further explore its potential mechanism, the target gene of hsa-miR-889-3p was predicted. Furthermore, hsa-miR-889-3p was confirmed to inhibit the expression of myeloid cell nuclear differentiation antigen (MNDA) in a targeted manner. In conclusion, hsa-miR-889-3p could promote the proliferation of osteosarcoma through inhibiting MNDA expression, which provides a potential therapeutic strategy in treatment for osteosarcoma.

Circulating, Cell-Free, MicroRNA Sequencing to Diagnose Cardiac Allograft Rejection and Distinguish Rejection Subtype

Summary of Objectives Genomic biomarkers are used to non-invasively screen cardiac transplant recipients for allograft rejection. Gene expression profiling has no ability to diagnose antibody-mediated rejection (AMR) and has a poor positive predictive value for T-cell mediated rejection (TCMR). An emerging class of genomic biomarkers are circulating, cell-free microRNAs (cf-miR). MicroRNAs modulate gene expression and have been implicated in rejection, they are found in the circulation, and early studies, using targeted genomic approaches suggest that cf-miRs may be a helpful biomarker to detect rejection. We hypothesize that cf-miRs can non-invasively diagnose rejection and distinguish AMR from TCMR. Methods The Genomic Research Alliance for Transplantation (GRAfT) is a prospective, multicenter study enrolling transplant recipients since 2014. All patients with AMR or TCMR were included and a group of controls without rejection were selected based on age, sex and race. Each biopsy was reviewed by two blinded, independent, expert cardiac pathologists. Plasma aliquots will undergo small molecular RNA isolation and the circulating cf-miR transcriptome will be sequenced using a next-generation platform. We expect to generate ∼6 million, single-end, 50bp reads per sample. Sequence data will be annotated using the FASTX_Toolkit and DESeq2 will be used to identify differentially expressed cf-miRs. Machine learning algorithms will be used to refine the cf-miR panel and maximize the C-statistic. Endpoints The study includes 35 patients with allograft rejection and 70 controls (Table). For the TCMR cohort there were 27 episodes of grade ≥ 2R rejection. For AMR there are 11 episodes of ≥ pAMR2 and 16 episodes of pAMR1 h or i. In total ∼300 plasma samples will be sequenced. Our primary objective is to develop a cf-miR panel that diagnoses allograft rejections, distinguishes rejection subtypes and allows for a blood-based, biochemical assessment of rejection severity.

Progress of microRNA in esophageal cancer

MicroRNA (miRNA) is a kind of small molecular non-coding RNA, which plays important roles in biological processes such as cell differentiation, proliferation, invasion and apoptosis by regulating the expression of target mRNA. Some miRNAs have the functions of oncogene or tumor suppressors in tumor genesis and development. In recent years, the study of miRNA on the early diagnosis, clinical staging, personalized treatment and prognostic evaluation in esophageal cancer is on the rise. Discoveries of miRNAs with close relations to esophageal cancer will be reviewed. Key words: MicroRNA; Esophageal neoplasms; Prognosis

Research progress of molecular mechanism on miR-29 family for regulating the formation, development and metastasis of breast cancer

MicroRNAs (miRNAs), a non-encoding small molecular RNA, is entitled to regulate gene expression after transcription, which plays a key role in the progress of tumorigenesis, growth and metastasis. MiR-29 family consists in miR-29a, miR-29b and miR-29c, all featured by the regulation of breast cancer. This review will summarize the regulation and molecular mechanism of miR-29 family in all critical stages of breast cancer, and evaluate the value of miR-29 as a new diagnostic and prognostic biomarker or therapeutic target. Key words: miR-29; Breast neoplasms; Gene regulation; Molecular mechanism

Updates in the research of relationship between MicroRNAs and hepatocellular carcinoma

MicroRNAs are one kind of endogenous non-coding small-molecular RNAs, which play an important role in regulating gene expression, cell proliferation and differentiation and a series of life activity. Hepatocellular carcinoma is a common malignant and life-threatening tumor with a high incidence and low 5-year survival rate. In recent years, the results of researches show that microRNAs in hepatocellular carcinoma have the function of oncogenes or tumor suppressor genes as well as having a close relationship with the occurrence, progression, diagnosis, treatment and prognosis of hepatocellular carcinoma. Key words: Liver neoplasms; MicroRNAs

Evolution Analysis About Soybean MIR166 Family

MicroRNA (miRNA) is a class of important regulating non-coding small molecular RNA. The gma-MIR166 gene family consists of 21 members and their expression patterns diversify widely. It is important to analyze the evolution of gma-MIR166 gene family in order to understand the evolutionary mechanisms of miRNAs in soybean. In this study, we implemented soybean wide genome block analysis, the molecular phylogeny of gma-MIR166 and block analysis of gma-MIR166 family. The results showed that both chromosome big segmental duplications and tandem duplications were main reasons contributed to the expanding of gma-MIR166 gene family. These findings suggested that gma-MIR166 gene family might originate from one or two ancient miRNA genes. The results of research provided a support for evolutionary study of miRNAs in soybean and related species in Fabaceae.

MicroRNA and diffuse large B-cell lymphoma

MicroRNA (miRNA) is a kind of naturally occurring short non-coding small molecular RNA,which regulates gene expression at the posttranscriptional level through its sequence complementation with target mRNAs.Researches have shown that different malignant tumors,including diffuse large B cell lymphoma,have specific miRNA expression profiles.Therefore,miRNAs expression level of specimens of body fluids and tissues is expected to be the new indicator for assessing diffuse large B cell lymphoma. Key words: MicroRNAs; Lymphoma, large B-cell, diffuse

Progress of microRNA in diagnosis and prognosis of diffuse large B cell lymphoma-review

MicroRNA (miRNA) is a class of naturally occurring short non-coding small molecular RNA with 19-25 nucleotide. MiRNA can regulate gene expression through incompletely binding to complementary sequences in the 3'UTR of target mRNA. MiRNA plays key regulatory role in a diverse rang of pathways, including cell proliferation, differentiation, apoptosis, stem cell development. Many studies have shown that many miRNA have a special role of gene regulation in cancer development and have been used as therapeutic targets and diagnostic markers of cancer. This review focuses on recent advances of studies on miRNA involved in tumorigenesis, and in classification, diagnosis, therapy and prognosis of DLBCL.

Identification of a latent pathogen on mulberry tree with a disease of mosaic dwarf

A disease on mulberries with the typical symptoms of mosaic and dwarf leaves was found in middle areas of China in 1980s. Presently, this disease became serious and spread out. Based on previous finding, we detected a viroid-like small molecular RNA in diseased mulberries tissues. In this paper, we further identified the pathogen of mulberry mosaic dwarf disease (MMDD) according to the Koch's postulates and reported the diagnostic method of the pathogen by using PCR with two sets of specific primers. The result might be helpful to control the disease extension.

Identification of a latent pathogen on mulberry tree with a disease of mosaic dwarf

A disease on mulberries with the typical symptoms of mosaic and dwarf leaves was found in middle areas of China in 1980s. Presently, this disease became serious and spread out. Based on previous finding, we detected a viroid-like small molecular RNA in diseased mulberries tissues. In this paper, we further identified the pathogen of mulberry mosaic dwarf disease (MMDD) according to the Koch's postulates and reported the diagnostic method of the pathogen by using PCR with two sets of specific primers. The result might be helpful to control the disease extension.