Identification Of miRNAs Research Articles

Genome-Wide Identification of miRNAs and Its Downstream Transcriptional Regulatory Network during Seed Maturation in Tilia tuan

Seed maturation not only determines the qualities and yields of seeds, but also affects seed storage and quality preservation. MicroRNAs (miRNAs) are a ubiquitous regulatory factor of gene expression in eukaryotes, which participate in the complex regulatory network of gene expression during seed maturation. However, miRNAs involved in maturation of Tilia tuan are still unknown. To reveal the role of miRNAs in T. tuan, small RNAs were profiled by high-throughput sequencing during seed maturation at five developmental stages. By predicting the target genes of miRNAs, the expression patterns of miRNAs during seed maturation were analyzed to identify those related to seed maturation. A total of 187 known miRNAs belonging to 42 miRNA families were found at five different seed maturation stages. Based on the analysis of unknown sequences, eight novel miRNAs were identified; 11,775 targets of 195 miRNAs were identified. Large numbers of miRNAs with diverse expression patterns, multiple-targeting and co-targeting of many miRNAs, and a complex regulatory network of miRNA-target genes were identified during seed maturation. These miRNAs and their targets may be involved in fatty acid, ABA, and lignin biosynthesis. Our study provides more information about the miRNA regulatory network and deepens our understanding of the function of miRNAs in T. tuan. miRNAs are revealed to be crucial during seed maturation, which provides a basis for further study of the regulatory role of miRNAs during seed maturation.

Identification and functional interpretation of miRNAs affected by rare CNVs in CAKUT

Rare copy number variants (CNVs) are among the most common genomic disorders underlying CAKUT. miRNAs located in rare CNVs represent well-founded functional variants for human CAKUT research. The study aimed to identify and functionally interpret miRNAs most frequently affected by rare CNVs in CAKUT and to estimate the overall burden of rare CNVs on miRNA genes in CAKUT. The additional aim of this study was to experimentally confirm the effect of a rare CNV in CAKUT on candidate miRNA’s expression and the subsequent change in mRNA levels of selected target genes. A database of CAKUT-associated rare CNV regions, created by literature mining, was used for mapping of the miRNA precursors. miRNAs and miRNA families, most frequently affected by rare CAKUT-associated CNVs, have been subjected to bioinformatic analysis. CNV burden analysis was performed to identify chromosomes with over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT. A functional study was performed on HEK293 MIR484+/- KO and HEK293 WT cell lines, followed by the analysis of relative miRNA and mRNA target gene levels. 80% of CAKUT patients with underlying rare CNV had at least one miRNA gene overlapping the identified CNV. Network analysis of the most frequently affected miRNAs has revealed the dominant regulation of the two miRNAs, hsa-miR-484 and hsa-miR-185-5p. Additionally, miR-548 family members have shown substantial enrichment in rare CNVs in CAKUT. An over/underrepresentation of miRNA genes in rare CNVs associated with CAKUT was observed in multiple chromosomes, such as chr16, chr20, and chr21. A significant 0.37 fold downregulation of hsa-miR-484, followed by a notable upregulation of MDM2 and APAF1 and downregulation of NOTCH3 was detected in HEK293 MIR484+/- KO compared to HEK293 WT cell lines, supporting the study hypothesis. miRNA genes are frequently affected by rare CNVs in CAKUT patients. Understanding the potential of CNV-affected miRNAs to participate in CAKUT as genetic drivers represent a crucial implication for the development of novel therapeutic approaches.

Genomics and transcriptomics to protect rice (Oryza sativa. L.) from abiotic stressors: -pathways to achieving zero hunger

More over half of the world's population depends on rice as a major food crop. Rice (Oryza sativa L.) is vulnerable to abiotic challenges including drought, cold, and salinity since it grown in semi-aquatic, tropical, or subtropical settings. Abiotic stress resistance has bred into rice plants since the earliest rice cultivation techniques. Prior to the discovery of the genome, abiotic stress-related genes were identified using forward genetic methods, and abiotic stress-tolerant lines have developed using traditional breeding methods. Dynamic transcriptome expression represents the degree of gene expression in a specific cell, tissue, or organ of an individual organism at a specific point in its growth and development. Transcriptomics can reveal the expression at the entire genome level during stressful conditions from the entire transcriptional level, which can be helpful in understanding the intricate regulatory network relating to the stress tolerance and adaptability of plants. Rice (Oryza sativa L.) gene families found comparatively using the reference genome sequences of other plant species, allowing for genome-wide identification. Transcriptomics via gene expression profiling which have recently dominated by RNA-seq complements genomic techniques. The identification of numerous important qtl,s genes, promoter elements, transcription factors and miRNAs involved in rice response to abiotic stress was made possible by all of these genomic and transcriptomic techniques. The use of several genomes and transcriptome methodologies to comprehend rice (Oryza sativa, L.) ability to withstand abiotic stress have been discussed in this review.

Identification of miRNA-mRNA-TFs regulatory network and crucial pathways involved in asthma through advanced systems biology approaches.

Asthma is a life-threatening and chronic inflammatory lung disease that is posing a true global health challenge. The genetic basis of the disease is fairly well examined. However, the molecular crosstalk between microRNAs (miRNAs), target genes, and transcription factors (TFs) networks and their contribution to disease pathogenesis and progression is not well explored. Therefore, this study was aimed at dissecting the molecular network between mRNAs, miRNAs, and TFs using robust computational biology approaches. The transcriptomic data of bronchial epithelial cells of severe asthma patients and healthy controls was studied by different systems biology approaches like differentially expressed gene detection, functional enrichment, miRNA-target gene pairing, and mRNA-miRNA-TF molecular networking. We detected the differential expression of 1703 (673 up-and 1030 down-regulated) genes and 71 (41 up-and 30 down-regulated) miRNAs in the bronchial epithelial cells of asthma patients. The DEGs were found to be enriched in key pathways like IL-17 signaling (KEGG: 04657), Th1 and Th2 cell differentiation (KEGG: 04658), and the Th17 cell differentiation (KEGG: 04659) (p-values = 0.001). The results from miRNAs-target gene pairs-transcription factors (TFs) have detected the key roles of 3 miRs (miR-181a-2-3p; miR-203a-3p; miR-335-5p), 6 TFs (TFAM, FOXO1, GFI1, IRF2, SOX9, and HLF) and 32 miRNA target genes in eliciting autoimmune reactions in bronchial epithelial cells of the respiratory tract. Through systemic implementation of comprehensive system biology tools, this study has identified key miRNAs, TFs, and miRNA target gene pairs as potential tissue-based asthma biomarkers.

Identification of miRNAs Mediating Seed Storability of Maize during Germination Stage by High-Throughput Sequencing, Transcriptome and Degradome Sequencing.

Seed storability is an important trait for improving grain quality and germplasm conservation, but little is known about the regulatory mechanisms and gene networks involved. MicroRNAs (miRNAs) are small non-coding RNAs regulating the translation and accumulation of their target mRNAs by means of sequence complementarity and have recently emerged as critical regulators of seed germination. Here, we used the germinating embryos of two maize inbred lines with significant differences in seed storability to identify the miRNAs and target genes involved. We identified a total of 218 previously known and 448 novel miRNAs by miRNA sequencing and degradome analysis, of which 27 known and 11 newly predicted miRNAs are differentially expressed in two maize inbred lines, as measured by Gene Ontology (GO) enrichment analysis. We then combined transcriptome sequencing and real-time quantitative polymerase chain reaction (RT-PCR) to screen and confirm six pairs of differentially expressed miRNAs associated with seed storability, along with their negative regulatory target genes. The enrichment analysis suggested that the miRNAs/target gene mediation of seed storability occurs via the ethylene activation signaling pathway, hormone synthesis and signal transduction, as well as plant organ morphogenesis. Our results should help elucidate the mechanisms through which miRNAs are involved in seed storability in maize.

MicroRNAs Dysregulation as Potential Biomarkers for Early Diagnosis of Endometriosis.

Endometriosis is a benign chronic disease in women that is characterized by the presence of active foci of the endometrium or endometrial tissue occurring outside of the uterus. The disease causes disabling symptoms such as pelvic pain and infertility, which negatively affect a patient’s quality of life. In addition, endometriosis imposes an immense financial burden on the healthcare system. At present, laparoscopy is the gold standard for diagnosing the disease because other non-invasive diagnostic tests have less accuracy. In addition, other diagnostic tests have low accuracy. Therefore, there is an urgent need for the development of a highly sensitive, more specific, and non-invasive test for the early diagnosis of endometriosis. Numerous researchers have suggested miRNAs as potential biomarkers for endometriosis diagnosis due to their specificity and stability. However, the greatest prognostic force is the determination of several miRNAs, the expression of which varies in a given disease. Despite the identification of several miRNAs, the studies are investigatory in nature, and there is no consensus on them. In the present review, we first provide an introduction to the dysregulation of miRNAs in patients with endometriosis and the potential use of miRNAs as biomarkers in the detection of endometriosis. Then we will describe the role of the mir-200 family in endometriosis. Several studies have shown that the expression of the mir-200 family changes in endometriosis patients, suggesting that they could be used as a diagnostic biomarker and therapeutic target for endometriosis.

Role of MicroRNAs in the Development of Chronic Liver Disease in Hepatitis Virus-Infected Egyptian Population

Background: The identification of miRNAs that play a role in the regulation of the viral life cycle and its related liver illness opens the door to the development of diagnostic biomarkers that can categorize patients at higher risk for developing end-stage liver disease. This study was designed to investigate the role of miRNAs in the development of viral hepatitis-induced chronic liver disease (CLD) in the Egyptian population, as well as their potential as possible diagnostic biomarkers for chronic hepatitis virus infection.
 Methodology: The study involved 100 CLD patients; 55 cases of hepatitis C virus (HCV) and 45 cases of non-viral hepatitis, in addition to 40 healthy controls. The expression of five miRNAs (miR‐30, miR‐122, miR‐296, miR‐351, and miR‐431) was assessed using real-time PCR.
 Results: Serum levels of miR‐30, miR‐122, miR‐296, miR‐351, and miR‐431 were significantly higher in all patients than the control group (p<0.01). Also, they were significantly greater in viral hepatitis cases compared to the non-viral hepatitis group (p<0.01). The sensitivities and specificities of miR-122a, miR‐30, miR‐296, miR‐351, and miR‐431 were (85.71%, 83.33%), (82.35%, 83.33%), (85.71%, 69.44%), (88.64%, 75.76%), and (87.80%, 65.79%), respectively.
 Conclusions: miR‐30, miR‐122, miR‐296, miR‐351, and miR‐431 play key roles in the development of CLD as a consequence of viral infection. So, they have the potential to be targeted for the early detection of chronic hepatitis virus infection and allow for exploring a new frontier in the discovery of innovative therapeutics to combat chronic viral infection and its serious life-threatening complications including liver cancer.

BLNIMDA: identifying miRNA-disease associations based on weighted bi-level network

BackgroundMicroRNAs (miRNAs) have been confirmed to be inextricably linked to the emergence of human complex diseases. The identification of the disease-related miRNAs has gradually become a routine way to unveil the genetic mechanisms of examined disorders.MethodsIn this study, a method BLNIMDA based on a weighted bi-level network was proposed for predicting hidden associations between miRNAs and diseases. For this purpose, the known associations between miRNAs and diseases as well as integrated similarities between miRNAs and diseases are mapped into a bi-level network. Based on the developed bi-level network, the miRNA-disease associations (MDAs) are defined as strong associations, potential associations and no associations. Then, each miRNA-disease pair (MDP) is assigned two information properties according to the bidirectional information distribution strategy, i.e., associations of miRNA towards disease and vice-versa. Finally, two affinity weights for each MDP obtained from the information properties and the association type are then averaged as the final association score of the MDP. Highlights of the BLNIMDA lie in the definition of MDA types, and the introduction of affinity weights evaluation from the bidirectional information distribution strategy and defined association types, which ensure the comprehensiveness and accuracy of the final prediction score of MDAs.ResultsFive-fold cross-validation and leave-one-out cross-validation are used to evaluate the performance of the BLNIMDA. The results of the Area Under Curve show that the BLNIMDA has many advantages over the other seven selected computational methods. Furthermore, the case studies based on four common diseases and miRNAs prove that the BLNIMDA has good predictive performance.ConclusionsTherefore, the BLNIMDA is an effective method for predicting hidden MDAs.

MicroRNAs in Various Body Fluids and their Importance in Forensic Medicine.

MicroRNAs (miRNAs) are a class of non-coding RNAs that regulate gene expression. miRNAs have tissue-specific expression and are also present in various extracellular body fluids, including blood, tears, semen, vaginal fluid, and urine. Additionally, the expression of miRNAs in body fluids is linked to various pathological diseases, including cancer and neurodegenerative diseases. Examination of body fluids is important in forensic medicine as they serve as a valuable form of evidence. Due to its stability, miRNA offers an advantage for body fluid identification, which can be detected even after several months or from compromised samples. Identification of unique miRNA profiles for different body fluids enables the identification of the body fluids. Furthermore, miRNAs profiling can be used to estimate post-mortem interval. Various biochemical and molecular methods used for the identification of miRNAs have shown promising results. We discuss different miRNAs as specific biomarkers and their clinical importance in different pathological conditions, as well as their medicolegal importance.

Identification of miRNAs Involved in Foetal Growth Restriction Due to Maternal Smoking during Pregnancy.

Introduction: Smoking during pregnancy is associated with reduced foetal growth, amongst other effects. Epigenetic modification in the foetus and placenta during embryonic development as a result of changes in the function of miRNAs is one of the pathophysiological mechanisms responsible for this. This dysregulation may be due to environmental changes or toxins such as tobacco. Objective: To study the impact of smoking during pregnancy and its role in intrauterine growth restriction via hypermethylated miRNAs. Materials and methods: The differences in methylation patterns for miRNAs in umbilical cord blood from low-birth-weight newborns of smoking mothers were compared with those from normal-weight newborns using MedIP-seq (StarArray). Results: Seven hypermethylated miRNAs were identified in the epigenetic study of cord blood from low-birth-weight newborns of smoking mothers in our sample. The miRNAs found to be hypermethylated were: MIR7-1, MIR3918, MIR1244-1, MIR4721, MIR25, MIR93, MIR3656. Conclusion: Intrauterine exposure to tobacco induces hypermethylation-mediated miRNA silencing in low-birth-weight newborns by modifying the expression of factors involved in vascular development, growth, and adaptation to hypoxia.

Identification of stage-associated exosome miRNAs in colorectal cancer by improved robust and corroborative approach embedded miRNA-target network.

BackgroundColorectal cancer (CRC) is a common gastrointestinal tumor with high morbidity and mortality. At the molecular level, patients at different stages present considerable heterogeneity. Although the miRNA in exosome is an effective biomarker to reveal tumor progression, studies based on stage-associated exosome miRNA regulatory network analysis still lacking. This study aims to identify CRC stage-associated exosome miRNAs and reveal their potential function in tumor progression.MethodsIn this study, serum and cellular exosome miRNA expression microarrays associated with CRC were downloaded from GEO database. Stage-common (SC) and stage-specific (SS) differentially expressed miRNAs were extracted and their targets were identified based on 11 databases. Furthermore, miRNA SC and SS regulatory function networks were built based on the CRC phenotypic relevance of miRNA targets, and the corresponding transcription factors were identified. Concurrently, the potential stage-associated miRNAs were identified by receiver-operating characteristic (ROC) curve analysis, survival analysis, drug response analysis, ceRNA analysis, pathway analysis and a comprehensive investigation of 159 publications.ResultsTen candidate stage-associated miRNAs were identified, with three SC (miR-146a-5p, miR-22-3p, miR-23b-3p) and seven SS (I: miR-301a-3p, miR-548i; IIIA: miR-23a-3p; IV: miR-194-3p, miR-33a-3p, miR-485-3p, miR-194-5p) miRNAs. Additionally, their targets were enriched in several vital cancer-associated pathways such as TGF-beta, p53, and hippo signaling pathways. Moreover, five key hotspot target genes (CCNA2, MAPK1, PTPRD, MET, and CDKN1A) were demonstrated to associated with better overall survival in CRC patients. Finally, miR-23b-3p, miR-301a-3p and miR-194-3p were validated being the most stably expressed stage-associated miRNAs in CRC serum exosomes, cell exosomes and tissues.ConclusionsThese CRC stage-associated exosome miRNAs aid to further mechanism research of tumor progression and provide support for better clinical management in patients with different stages.

A Novel Strategy for Identifying NSCLC MicroRNA Biomarkers and Their Mechanism Analysis Based on a Brand-New CeRNA-Hub-FFL Network.

Finding reliable miRNA markers and revealing their potential mechanisms will play an important role in the diagnosis and treatment of NSCLC. Most existing computational methods for identifying miRNA biomarkers only consider the expression variation of miRNAs or rely heavily on training sets. These deficiencies lead to high false-positive rates. The independent regulatory model is an important complement to traditional models of co-regulation and is more impervious to the dataset. In addition, previous studies of miRNA mechanisms in the development of non-small cell lung cancer (NSCLC) have mostly focused on the post-transcriptional level and did not distinguish between NSCLC subtypes. For the above problems, we improved mainly in two areas: miRNA identification based on both the NOG network and biological functions of miRNA target genes; and the construction of a 4-node directed competitive regulatory network to illustrate the mechanisms. NSCLC was classified as lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) in this work. One miRNA biomarker of LUAD (miR-708-5p) and four of LUSC (miR-183-5p, miR-140-5p, miR-766-5p, and miR-766-3p) were obtained. They were validated using literature and external datasets. The ceRNA-hub-FFL involving transcription factors (TFs), microRNAs (miRNAs), mRNAs, and long non-coding RNAs (lncRNAs) was constructed. There were multiple interactions among these components within the net at the transcriptional, post-transcriptional, and protein levels. New regulations were revealed by the network. Meanwhile, the network revealed the reasons for the previous conflicting conclusions on the roles of CD44, ACTB, and ITGB1 in NSCLC, and demonstrated the necessity of typing studies on NSCLC. The novel miRNA markers screening method and the 4-node directed competitive ceRNA-hub-FFL network constructed in this work can provide new ideas for screening tumor markers and understanding tumor development mechanisms in depth.

Identification of miRNA-mRNA Networks Associated with Pigeon Skeletal Muscle Development and Growth.

Simple SummaryElucidating the molecular mechanisms that regulate the growth and development of skeletal muscle is an essential prerequisite for using molecular breeding technology to improve the meat production of pigeons. In the present study, we characterized the expression of miRNAs and mRNAs in pigeon skeletal muscle at two embryonic stages (E8 and E13) and two growth stages (D1 and D10). A total of 839 DEmiRNAs and 11,311 DEGs were identified among the four groups. An miRNA–mRNA network was constructed by correlation analysis and target prediction between DEmiRNAs and DEGs. Based on the connectivity degree, twenty potential hub miRNAs responsible for pigeon skeletal muscle development and growth were identified, including cli-miR-20b-5p, miR-130-y, cli-miR-106-5p, cli-miR-181b-5p, miR-1-z, etc. GO and KEGG enrichment analysis identified candidate biological processes and pathways related to pigeon skeletal muscle development and growth. Our results provide a database for further investigating the miRNA–mRNA regulatory mechanism underlying pigeon skeletal muscle development and growth.The growth and development of skeletal muscle determine the productivity of pigeon meat production, and miRNA plays an important role in the growth and development of this type of muscle. However, there are few reports regarding miRNA regulating the growth and development of skeletal muscle in pigeons. To explore the function of miRNA in regulating the growth and development of pigeon skeletal muscle, we used RNA sequencing technology to study the transcriptome of pigeons at two embryonic stages (E8 and E13) and two growth stages (D1 and D10). A total of 32,527 mRNAs were identified in pigeon skeletal muscles, including 14,378 novel mRNAs and 18,149 known mRNAs. A total of 2362 miRNAs were identified, including 1758 known miRNAs and 624 novel miRNAs. In total, 839 differentially expressed miRNAs (DEmiRNAs) and 11,311 differentially expressed mRNAs (DEGs) were identified. STEM clustering analysis assigned DEmiRNAs to 20 profiles, of which 7 were significantly enriched (p-value < 0.05). These seven significantly enriched profiles can be classified into two categories. The first category represents DEmiRNAs continuously downregulated from the developmental stage to the growth stage of pigeon skeletal muscle, and the second category represents DEmiRNAs with low expression at the development and early growth stage, and significant upregulation at the high growth stage. We then constructed an miRNA–mRNA network based on target relationships between DEmiRNAs and DEGs belonging to the seven significantly enriched profiles. Based on the connectivity degree, 20 hub miRNAs responsible for pigeon skeletal muscle development and growth were identified, including cli-miR-20b-5p, miR-130-y, cli-miR-106-5p, cli-miR-181b-5p, miR-1-z, cli-miR-1a-3p, miR-23-y, cli-miR-30d-5p, miR-1-y, etc. The hub miRNAs involved in the miRNA–mRNA regulatory networks and their expression patterns during the development and growth of pigeon skeletal muscle were visualized. GO and KEGG enrichment analysis found potential biological processes and pathways related to muscle growth and development. Our findings expand the knowledge of miRNA expression in pigeons and provide a database for further investigation of the miRNA–mRNA regulatory mechanism underlying pigeon skeletal muscle development and growth.

Identification of Novel miRNAs, Targeting Genes, Signaling Pathway, and the Small Molecule for Overcoming Oxaliplatin Resistance of Metastatic Colorectal Cancer.

One of the globally common cancers is colorectal cancer (CRC). At present, a surgical approach remains a good option for CRC patients; however, 20% of surgically treated CRC patients experience metastasis. Currently, even the first-line used drug, oxaliplatin, remains inadequate for treating metastatic CRC, and its side effect of neurotoxicity is a major problem when treating CRC. The Gene Omnibus GSE42387 database contains gene expression profiles of parental and oxaliplatin-resistant LoVo cell lines. Differentially expressed genes (DEGs) between parental and oxaliplatin-resistance LoVo cells, protein-protein interactions (PPIs), and a pathway analysis were determined to identify overall biological changes by an online DAVID bioinformatics analysis. The ability of DEGs to predict overall survival (OS) and disease-free survival (DFS) was validated by the SPSS 22.0, using liver metastasis CRC patient samples of GSE41258. The bioinformatics web tools of the GEPIA, the Human Protein Atlas, WebGestalt, and TIMER platforms were used. In total, 218 DEGs were identified, among which 105 were downregulated and 113 were upregulated. After mapping the PPI networks and pathways, 60 DEGs were identified as hub genes (with high degrees). Six genes (TGFB1, CD36, THBS1, FABP1, PCK1, and IRS1) were involved with malaria, PPAR signaling, and the adipocytokine signaling pathway. High expressions of CD36 and PCK1 were associated with the poor survival of CRC patients in the GSE41258 database. We predicted specific micro (mi)RNAs that targeted the 3′ untranslated region (UTR) of PCK1 by using miRWalk. It was found that three miRNAs, viz., miR-7-5p, miR-20a-3p, and miR-636, may be upstream targets of those genes. High expression levels of miR-7-5p, miR-20a-3p, and miR-636 were associated with poor OS of CRC patients, and the small-molecule compound, mersalyl, is a promising drug for treating oxaliplatin-resistant CRC. In conclusion, miR-7-5p miR-20a-3p, and miR-636 targeted the PCK1 biomarker in the PPAR signaling pathway, which is involved in oxaliplatin-resistant CRC. Meanwhile, mersalyl was identified as a potential drug for overcoming oxaliplatin resistance in CRC. Our findings may provide novel directions and strategies for CRC therapies.

Identification of miRNAs and their target genes associated with improved maize seed vigor induced by gibberellin.

High seed vigor is crucial for agricultural production owing to its potential in high quality and yield of crops and a better understanding of the molecular mechanism associated with maize seed vigor is highly necessary. To better understand the involvement and regulatory mechanism of miRNAs correlated with maize seed vigor, small RNAs and degradome sequencing of two inbred lines Yu537A and Yu82 were performed. A total of 791 mature miRNAs were obtained with different expressions, among of which 505 miRNAs were newly identified and the rest miRNAs have been reported before by comparing the miRNAs with the sequences in miRbase database. Analysis of miRNA families showed maize seeds contain fewer miRNA families and larger miRNA families compared with animals, indicating that functions of miRNAs in maize seeds were more synergistic than animals. Degradome sequencing was used to identify the targets of miRNAs and the results showed a total of 6,196 targets were obtained. Function analysis of differentially expressed miRNAs and targets showed Glycan degradation and galactose metabolism were closely correlated with improved maize seed vigor. These findings provide valuable information to understand the involvement of miRNAs with maize seed vigor and these putative genes will be valuable resources for improving the seed vigor in future maize breeding.

Identification of miRNAs and Target Genes at Key Stages of Sexual Differentiation in Androdioecious Osmanthus fragrans.

Androdioecy is the crucial transition state in the evolutionary direction of hermaphroditism to dioecy, however, the molecular mechanisms underlying the formation of this sex system remain unclear. While popular in China for its ornamental and cultural value, Osmanthus fragrans has an extremely rare androdioecy breeding system, meaning that there are both male and hermaphroditic plants in a population. To unravel the mechanisms underlying the formation of androdioecy, we performed small RNA sequencing studies on male and hermaphroditic O. fragrans. A total of 334 miRNAs were identified, of which 59 were differentially expressed. Functional categorization revealed that the target genes of differentially expressed miRNAs were mainly involved in the biological processes of reproductive development and the hormone signal transduction pathway. We speculated that the miRNA160, miRNA167, miRNA393 and miRNA396 families may influence the sex differentiation in O. fragrans. Overall, our study is the first exploration of miRNAs in the growth and development process of O. fragrans, and is also the first study of androdioecious plants from the miRNA sequencing perspective. The analysis of miRNAs and target genes that may be involved in the sex differentiation process lay a foundation for the ultimate discovery of the androdioecious molecular mechanism in O. fragrans.

Identification and characterization of miRNAs and PHAS loci related to the early development of the embryo and endosperm in Fragaria × ananassa

BackgroundThe strawberry fleshy fruit is actually enlarged receptacle tissue, and the successful development of the embryo and endosperm is essential for receptacle fruit set. MicroRNAs (miRNAs) and phased small interfering RNAs (phasiRNAs) play indispensable regulatory roles in plant growth and development. However, miRNAs and phasiRNAs participating in the regulation of strawberry embryo and endosperm development have yet to be explored.ResultsHere, we performed genome-wide identification of miRNA and phasiRNA-producing loci (PHAS) in strawberry seeds with a focus on those involved in the development of the early embryo and endosperm. We found that embryos and endosperm have different levels of small RNAs. After bioinformatics analysis, the results showed that a total of 404 miRNAs (352 known and 52 novel) and 156 PHAS genes (81 21-nt and 75 24-nt genes) could be found in strawberry seed-related tissues, of which four and nine conserved miRNA families displayed conserved expression in the endosperm and embryo, respectively. Based on refined putative annotation of PHAS loci, some auxin signal-related genes, such as CM3, TAR2, AFB2, ASA1, NAC and TAS3, were found, which demonstrates that IAA biosynthesis is important for endosperm and embryo development during early fruit growth. Additionally, some auxin signal-related conserved (miR390-TAS3) and novel (miR156-ASA1) trigger-PHAS pairs were identified.ConclusionsTaken together, these results expand our understanding of sRNAs in strawberry embryo and endosperm development and provide a genomic resource for early-stage fruit development.

MicroRNA expression profiles of peripheral blood and mononuclear cells in myasthenia gravis: A systematic review

BackgroundStudies have described the role of microRNAs (miRNAs) in thymic function, along with directly observing the altered expression of miRNAs in thymuses of myasthenia gravis (MG) patients; so, miRNAs became a core component in the pathophysiology of MG. However, because the miRNA analysis results are contradictory, the identification of MG-related miRNAs is daunting. ObjectiveWe did a systematic review of studies analyzing the miRNA expression profile of peripheral blood and mononuclear cells for patients with MG. MethodsWe ran a database search in PubMed, Scopus, and Web of Science on August 17, 2021. Original articles that analyzed miRNA profiles in peripheral blood (serum, plasma, and whole blood) and peripheral blood mononuclear cells (PBMCs) for patients with MG in comparison with a non-MG or healthy control (HC) group were eligible. The quality of studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Results26 studies were included. The quality of studies was fair (median score, 5). Among 226 different miRNAs that were deregulated in at least one study (range, 1–87), ten miRNAs were significantly deregulated in three or more studies. Five miRNAs (50%) showed the same deregulation: miR-106b-3p and miR-21-5p were consistently upregulated, and miR-20b, miR-15b, and miR-16 were consistently downregulated. Also, there were five miRNAs that were mostly upregulated, miR-150-5p, miR-146a, miR-30e-5p, and miR-338-3p, or downregulated, miR-324-3p, across studies. ConclusionThese miRNAs contribute to different pathways, importantly neural apoptosis and autophagy, inflammation, T regulatory cell development, and T helper cell balance. Prior to being used for diagnostic and therapeutic purposes, it is required to pursue molecular mechanisms these consistently and mostly dysregulated miRNAs specifically use in the context of MG.

Identification of therapeutic miRNAs from the arsenic induced gene expression profile of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is the most common primary liver cancer, with a rising worldwide burden due to a lack of efficient treatment techniques and diagnosis after it has metastasized. Therefore, small non-coding RNA (miRNAs) as protein translation inhibitors are gaining attention that degrades or suppress specific gene transcripts, making it a prime strategy for oncogenes or tumor suppression. Systematic research with miRNAs in combination with Arsenic, which has been employed as a drug to treat several diseases, including cancer, was focused on cellular responses through interacting with multiple biological targets. The differential gene expression of the DNA microarray dataset (GSE48441) revealed the association of sterol, cholesterol, and lipid metabolic processes. With the aid of the network pharmacology approach, hsa-mir-335-5p was uncovered to negatively regulate the important nodes driving the transport and utilization of essential compounds for the rapid growth and proliferation of cancer cells. The binding energies of the duplexes were validated by the minimal free energies of the mRNAs for hsa-mir-335-5p, indicating energetically desirable binding association. The molecular interactions between hsa-mir-335-5p, which interacts with the Argonaute protein in the RNA induced silencing complex, and the target-specific genes were also investigated, revealing its susceptibility to be employed in in vitro studies.

Identification of potential core genes and miRNAs in pediatric ACC via bioinformatics analysis.

Pediatric adrenocortical carcinomas (ACC) are rare aggressive neoplasms with heterogeneous prognosis, and often produce a most lethal malignant tumor, whereas its aetiology is still unclear. The aim of the present study was to identify the factors responsible for the development of pediatric ACC, a better understanding of the disease, and investigate new molecular biomarkers and therapeutic targets. To identify the key genes and miRNAs linked to pediatric ACC, as well as their potential molecular mechanisms, the GSEGSE75415 and GSE169253 microarray datasets were analyzed. A total of 329 differentially produced genes (DEGs) and 187 differentially produced miRNAs (DEMs) were obtained after analyzing the GSEGSE75415 and GSE169253 datasets, respectively. Next, 3,359 genes were obtained by overlapping the target mRNAs of DEMs. Following protein-protein interaction network and Gene Ontology analysis, the ten nodes with the highest degrees were screened as hub genes. Among them, the highly expressed hub genes, MAPK1 and EP300, were associated with a worse overall survival. Additionally, hsa-miR-376, hsa-miR-148, hsa-miR-139, and hsa-miR-1305 were strongly associated with poorer survival. We proposed that the hub genes (MAPK1, EP300, hsa-miR-376, hsa-miR-148, hsa-miR-139, and hsa-miR-1305) may have a definite impact on cellular proliferation and migration in adrenocortical tumors. The roles of these hub genes in adrenocortical tumors may provide novel insight to improve the diagnosis and treatment of patients with pediatric ACC.