miRNA Function Research Articles

Deciphering the role of miR-71 and let-7 in the fertility of cystic echinococcosis cysts: a preliminary assessment.

Cystic echinococcosis(CE) is a neglected helminthic zoonosis in many parts of the world. Some CE cysts in the intermediate host are non-fertile. Considering the function of microRNAs in many biological processes such as embryonic development, cell proliferation, and apoptosis, this study investigated the function and comparison of miR-71 and let-7 in fertile and non-fertile CE cysts. Here, we determined the expression level of the miRNAs for 33 animal cysts and 16 human cysts (Echinococcus granulosus sensu stricto (G1). The quantitative real-time PCR method was conducted for the expression evaluation of miR-71 and let-7. The expression of both miRNAs in all samples was determined using the following formula: [ΔCT = CT (target) - CT (internal control)]. A comparison of Δct of miR-71 and let-7 in fertile and non-fertile cysts did not show a significant difference (P = 0.911 and 0.354). In cattle, sheep, and humans, Δct of miR-71, and let-7 were higher, respectively. Therefore, the mean expression of miR-71 and let-7 indicates an increase in humans compared to other intermediate hosts. Also, statistical results show a significant difference in the expression of these miRNAs in sheep, cattle, and human cysts (P = 0.025 and 0.01). The lower expression of these miRNAs in cattle cysts and their common infertility might be associated with the hypothesis and function of miRNAs in the fertility of CE cysts. So we should not ignore the function and role of miRNAs in this subject due to the importance of infertility in E. granulosus epidemiology.

Carcinogenic effects of heavy metals by inducing dysregulation of microRNAs: A review.

Heavy metal exposure has soared due to the twentieth century's industrial activity. The most common heavy metals that lead to human poisoning are mercury, cadmium, and arsenic. Acute or chronic poisoning may develop following exposure to water, air, or food, so the bioaccumulation of these heavy metals causes harmful consequences in various human tissues and organs. Heavy metals interfere with biological functions such as growth, proliferation, differentiation, damage repair, and apoptosis. The mechanisms of action for these metals to cause toxicity are similar, including forming reactive oxygen species (ROS), weakening antioxidant defenses, enzyme inactivation, and oxidative stress. Heavy metal exposure is mainly associated with skin, liver, prostate, lung, urinary bladder, thyroid, and kidney cancers, as well as causing gastrointestinal malignancies. Several microRNAs (miRNAs or miRs) have been involved in various human cancers due to the dysregulation of miRNA function. Recent investigations have confirmed that microRNA dysregulation plays a role in the carcinogenesis of many tissues. This review presents the data concerning arsenic, cadmium, and mercury metals and their contamination sources, human exposure, toxicity, and inducing malignant transformations such as carcinogenicity in in-vitro or in-vivo specimens or dysregulated expression of microRNAs.

Bioinformatics Analysis of Common Genetic and Molecular Traits and Association of Portal Hypertension with Pulmonary Hypertension.

Portal hypertension (PH) is an important cause of pulmonary arterial hypertension(PAH), but its mechanism is still unclear. We used genetic data analysis to explore the shared genes and molecular mechanisms of PH and PAH. We downloaded the PH and PAH data from the GEO database, and used the weighted gene coexpression network analysis method (WGCNA) to analyze the coexpression modules of idiopathic noncirrhotic portal hypertension (INCPH) and cirrhotic portal hypertension (CPH) and pulmonary hypertension, respectively. Enrichment analysis was performed on the common genes, and differential gene expressions (DEGs) were used for verification. The target genes of INCPH and PAH were obtained by string and cytoscape software, and the miRNAs of target genes were predicted by miRwalk, miRDB, and TargetScan and their biological functions were analyzed; finally, we used PanglaoDB to predict the expression of target genes in cells. In WGCNA, gene modules significantly related to PAH, CPH, and INCPH were identified, and enrichment function analysis showed that the common pathway of PAH and CPH were “P53 signaling pathway,” “synthesis of neutral lipids”; PAH and INCPH are “terminal,” “Maintenance Regulation of Granules,” and “Toxin Transport.” DEGs confirmed the results of WGCNA; the common miRNA functions of PAH and cirrhosis were enriched for “P53 signaling pathway,” “TGF-β signaling pathway,” “TNF signaling pathway,” and “fatty acid metabolism,” and the miRNAs-mRNAs network suggested that hsa-miR-22a-3p regulates MDM2 and hsa-miR-34a-5p regulates PRDX4; the target genes of PAH and INCPH are EIF5B, HSPA4, GNL3, RARS, UTP20, HNRNPA2B1, HSP90B1, METAP2, NARS, SACM1L, and their target miRNA function enrichment showed EIF5B, HNRNPA2B1, HSP90B1, METAP2, NARS, SACM1L, and HSPA4 are associated with telomeres and inflammation, panglaoDB showed that target genes are located in endothelial cells, smooth muscle cells, etc. In conclusion, the mechanism of pulmonary hypertension induced by portal hypertension may be related to telomere dysfunction and P53 overactivation, and lipid metabolism and intestinal inflammation are also involved in this process.

Identification of Candidate Genes and Regulatory Competitive Endogenous RNA (ceRNA) Networks Underlying Intramuscular Fat Content in Yorkshire Pigs with Extreme Fat Deposition Phenotypes.

Intramuscular fat (IMF) content is vital for pork quality, serving an important role in economic performance in pig industry. Non-coding RNAs, with mRNAs, are involved in IMF deposition; however, their functions and regulatory mechanisms in porcine IMF remain elusive. This study assessed the whole transcriptome expression profiles of the Longissimus dorsi muscle of pigs with high (H) and low (L) IMF content to identify genes implicated in porcine IMF adipogenesis and their regulatory functions. Hundreds of differentially expressed RNAs were found to be involved in fatty acid metabolic processes, lipid metabolism, and fat cell differentiation. Furthermore, combing co-differential expression analyses, we constructed competing endogenous RNAs (ceRNA) regulatory networks, showing crosstalk among 30 lncRNAs and 61 mRNAs through 20 miRNAs, five circRNAs and 11 mRNAs through four miRNAs, and potential IMF deposition-related ceRNA subnetworks. Functional lncRNAs and circRNAs (such as MSTRG.12440.1, ENSSSCT00000066779, novel_circ_011355, novel_circ_011355) were found to act as ceRNAs of important lipid metabolism-related mRNAs (LEP, IP6K1, FFAR4, CEBPA, etc.) by sponging functional miRNAs (such as ssc-miR-196a, ssc-miR-200b, ssc-miR10391, miR486-y). These findings provide potential regulators and molecular regulatory networks that can be utilized for research on IMF traits in pigs, which would aid in marker-assisted selection to improve pork quality.

Identify miRNA-mRNA regulation pairs to explore potential pathogenesis of lung adenocarcinoma.

MicroRNA (miRNA) function via base-pairing with complementary sequences within mRNA molecules. This study aims to identify critical miRNA-mRNA regulation pairs contributing to lung adenocarcinoma (LUAD) pathogenesis. MiRNA and mRNA microarray and RNA-sequencing datasets were downloaded from gene expression omnibus (GEO) and the cancer genome atlas (TCGA) databases. Differential miRNAs (DE-miRNAs) and mRNAs (DE-mRNAs) were screened by the GEO2R tool and R packages. DAVID, DIANA, and Hiplot tools were used to perform gene enrichment analysis. The pairs of miRNA-mRNA were screened from the experimentally validated miRNA-target interactions databases (miRTarBase and TarBase). External validation was carried out in 30 pairs of LUAD tissues by quantitative reverse transcription and polymerase chain reaction (qRT-PCR). The diagnostic value of the miRNA-mRNA regulation pairs was evaluated by receiver operating characteristic curve (ROC) and decision curve analysis (DCA). Biological function assay was were also performed to confirm the function of miRNA-mRNA axis in LUAD progression. The study also performed the clinical, survival and tumor-associated phenotypic analysis of miRNA-mRNA pairs. A total of 7 miRNA and 13 mRNA expression datasets from GEO were analyzed, and 11 DE-miRNAs (5 down-regulated and 6 up-regulated in LUAD tissues) and 128 DE-mRNAs (30 up-regulated and 98 down-regulated in LUAD tissues) were identified. The pairs of miR-1-3p(down) and CENPF(up) and miR-126-5p(down) and UGT8(up) were verified in the external validation cohort (30 LUAD vs. 30 NC) using qRT-PCR. Areas under the ROC curve of the two miRNA-mRNA regulation pairs panel were 0.973 in TCGA-LUAD and 0.771 in the external validation. The DCA also showed that the miRNA-mRNA regulation pairs had an excellent diagnostic performance distinguishing LUAD from normal controls. The expression of the regulation pairs is different in different ages, TNM stages, and gender. The overexpression of miR-1-3p and miR-126-5p significantly inhibited the proliferation and migration of LUAD cells. Correlation analysis showed that CENPF correlated with prognosis and tumor immunity. The research identified potential miRNA-mRNA regulation pairs, providing a new idea for exploring the genesis and development of LUAD.

Roles of non-coding RNAs in the hormonal and nutritional regulation in nodulation and nitrogen fixation.

Symbiotic nitrogen fixation is an important component in the nitrogen cycle and is a potential solution for sustainable agriculture. It is the result of the interactions between the plant host, mostly restricted to legume species, and the rhizobial symbiont. From the first encounter between the host and the symbiont to eventual successful nitrogen fixation, there are delicate processes involved, such as nodule organogenesis, rhizobial infection thread progression, differentiation of the bacteroid, deregulation of the host defense systems, and reallocation of resources. All these processes are tightly regulated at different levels. Recent evidence revealed that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), participate in these processes by controlling the transcription and translation of effector genes. In general, ncRNAs are functional transcripts without translation potential and are important gene regulators. MiRNAs, negative gene regulators, bind to the target mRNAs and repress protein production by causing the cleavage of mRNA and translational silencing. LncRNAs affect the formation of chromosomal loops, DNA methylation, histone modification, and alternative splicing to modulate gene expression. Both lncRNAs and circRNAs could serve as target mimics of miRNA to inhibit miRNA functions. In this review, we summarized and discussed the current understanding of the roles of ncRNAs in legume nodulation and nitrogen fixation in the root nodule, mainly focusing on their regulation of hormone signal transduction, the autoregulation of nodulation (AON) pathway and nutrient homeostasis in nodules. Unraveling the mediation of legume nodulation by ncRNAs will give us new insights into designing higher-performance leguminous crops for sustainable agriculture.

MicroRNAs in extracellular vesicles: Sorting mechanisms, diagnostic value, isolation, and detection technology

MicroRNAs (miRNAs) are a class of short, single-stranded, noncoding RNAs, with a length of about 18-22 nucleotides. Extracellular vesicles (EVs) are derived from cells and play a vital role in the development of diseases and can be used as biomarkers for liquid biopsy, as they are the carriers of miRNA. Existing studies have found that most of the functions of miRNA are mainly realized through intercellular transmission of EVs, which can protect and sort miRNAs. Meanwhile, detection sensitivity and specificity of EV-derived miRNA are higher than those of conventional serum biomarkers. In recent years, EVs have been expected to become a new marker for liquid biopsy. This review summarizes recent progress in several aspects of EVs, including sorting mechanisms, diagnostic value, and technology for isolation of EVs and detection of EV-derived miRNAs. In addition, the study reviews challenges and future research avenues in the field of EVs, providing a basis for the application of EV-derived miRNAs as a disease marker to be used in clinical diagnosis and even for the development of point-of-care testing (POCT) platforms.

Identification and Characterization of Salt-Responsive MicroRNAs in Taxodium hybrid ‘Zhongshanshan 405’ by High-Throughput Sequencing

MicroRNAs (miRNAs) are a type of noncoding RNA participating in the post-transcriptional regulation of gene expression that regulates plant responses to salt stress. Small RNA sequencing was performed in this study to discover the miRNAs responding to salt stress in Taxodium hybrid ‘Zhongshanshan 405’, which is tolerant to salinity stress. A total of 52 miRNAs were found to be differentially expressed. The target genes were enriched with gene ontology (GO), including protein phosphorylation, cellular response to stimulus, signal transduction, ATP and ADP binding, showing that miRNAs may play key roles in regulating the tolerance to salt stress in T. hybrid ‘Zhongshanshan 405’. Notably, a G-type lectin S-receptor-like serine/threonine-protein kinase (GsSRK) regulated by novel_77 and novel_2 miRNAs and a mitogen-activated protein kinase kinase kinase (MAPKKK) regulated by novel_41 miRNA were discovered under both short- and long-term salt treatments and can be selected for future research. This result provides new insights into the regulatory functions of miRNAs in the salt response of T. hybrid ‘Zhongshanshan 405’.

Gga-miR-449b-5p Regulates Steroid Hormone Synthesis in Laying Hen Ovarian Granulosa Cells by Targeting the IGF2BP3 Gene.

Simple SummaryThe aim of this study was to explore the regulatory effect of gga-miR-449b-5p on GC proliferation and steroidogenesis in laying hens. Our results showed that gga-miR-449b-5p had no effect on the proliferation of GCs, but regulated the expression of key genes involved in steroid synthesis and the secretion of P4 and E2. In addition, gga-miR-449b-5p could target IGF2BP3 and inhibit its mRNA and protein expression. Therefore, we concluded that gga-miR-449b-5p played an important role in the synthesis of steroid hormones in laying hens.MiRNAs have been found to be involved in the regulation of ovarian function as important post-transcriptional regulators, including regulators of follicular development, steroidogenesis, cell atresia, and even the development of ovarian cancer. In this study, we evaluated the regulatory role of gga-miR-449b-5p in follicular growth and steroid synthesis in ovarian granulosa cells (GCs) of laying hens through qRT-PCR, ELISAs, western blotting and dual-luciferase reporter assays, which have been described in our previous study. We demonstrated that gga-miR-449b-5p was widely expressed in granulosa and theca layers of the different-sized follicles, especially in the granulosa layer. The gga-miR-449b-5p had no significant effect on the proliferation of GCs, but could significantly regulate the expression of key steroidogenesis-related genes (StAR and CYP19A1) (p < 0.01) and the secretion of P4 and E2 (p < 0.01 and p < 0.05). Further research showed that gga-miR-449b-5p could target IGF2BP3 and downregulate the mRNA and protein expression of IGF2BP3 (p < 0.05). Therefore, this study suggests that gga-miR-449b-5p is a potent regulator of the synthesis of steroid hormones in GCs by targeting the expression of IGF2BP3 and may contribute to a better understanding of the role of functional miRNAs in laying hen ovarian development.

Predicting miRNA-disease association through combining miRNA function and network topological similarities based on MINE

Predicting associations between microRNAs (miRNAs) and diseases from the viewpoint of function modules has become increasingly popular. However, existing methods obtained the relations between diseases and miRNAs only through the construction of similarity networks and neglected the complex network characteristic. In this paper, a new method named combining miRNA function similarities and network topology similarities based on module identification in networks (ComSim-MINE) was developed. Combined similarity is calculated from the harmonic mean between miRNA function similarities and network topology similarities. Experimental results showed that ComSim-MINE can compete with several state-of-the-art weighted function module algorithms, such as ClusterONE, MCODE, NEMO, and SPICi, and achieved the satisfactory results in terms of the composite score of F-measure, sensitivity, and accuracy based on the generated miRNA function interaction network. From the analysis of case studies, some new findings obtained from our proposed method provide clinicians new clues for epidemic diseases, such as COVID-19.

Differential expression of miRNAs in bronchoalveolar lavage fluid and plasma from patients with chronic obstructive pulmonary disease.

Micro RNAs (MiRNAs) act as a key regulator participating in various biological process, and the roles of that play in chronic obstructive pulmonary disease (COPD) are discovered. However, recent pharmacological treatment for COPD focus on alleviating symptoms and reducing the risk events. The heterogeneous COPD causes variable responses to pharmacological interventions. COPD treatment has gradually developed into precision medicine, integrating clinical and biomarker information to optimize personalized therapy. Thus, targeting miRNAs represents a promising strategy for COPD individual therapy. Twelve COPD patients, 7 community-acquired pneumonia and 4 normal people were recruited. Total RNAs were collected from the bronch alveolar lavage cells and peripheral blood plasma of each participant. miRNAs were profiled by microarray and systematically compared between patients with different groups. Bioinformatic analysis identified pathways relevant to the pathogenesis of COPD. Next, the target pathway networks were mapped. Compared different groups, we obtain differential expression of miRNAs (Q value (Adjusted P value) < .05 and |log2FC| >2). Gene ontology enrichment analyses showed that differentially expressed miRNAs function as regulators in different modules of cellular component, molecular function and biological process. Kyoto Encyclopedia of Genes and Genomes enrichment analyses suggested that signals, such as MAPK signaling pathway, Ras signaling pathway, FoxO signaling pathway and oxidative stress may participate in the pathogenesis of COPD. In the miRNAs target pathway networks, novel-hsa-miR26-3p or hsa-miR-3529-3p/CDC42/MAPK signaling pathway may play a role in regulating COPD. Our findings demonstrate critical roles of the miRNAs in COPD molecular pathology. The data support a plausible mechanism that miRNAs may be involved in the development of COPD by affecting the inflammatory and oxidative stress. Moreover, hsa-miR-4748/CDC42/MAPK signaling pathway may contribute to the pathogenesis of COPD, providing a potential novel therapeutic strategy in COPD.

Mesenchymal stromal cells for the treatment of Alzheimer's disease: Strategies and limitations.

Alzheimer’s disease (AD) is a major cause of age-related dementia and is characterized by progressive brain damage that gradually destroys memory and the ability to learn, which ultimately leads to the decline of a patient’s ability to perform daily activities. Although some of the pharmacological treatments of AD are available for symptomatic relief, they are not able to limit the progression of AD and have several side effects. Mesenchymal stem/stromal cells (MSCs) could be a potential therapeutic option for treating AD due to their immunomodulatory, anti-inflammatory, regenerative, antioxidant, anti-apoptotic, and neuroprotective effects. MSCs not only secret neuroprotective and anti-inflammatory factors to promote the survival of neurons, but they also transfer functional mitochondria and miRNAs to boost their bioenergetic profile as well as improve microglial clearance of accumulated protein aggregates. This review focuses on different clinical and preclinical studies using MSC as a therapy for treating AD, their outcomes, limitations and the strategies to potentiate their clinical translation.

MiR2Trait: an integrated resource for investigating miRNA-disease associations.

MicroRNAs are key components of cellular regulatory networks, and breakdown in miRNA function causes cascading effects leading to pathophenotypes. A better understanding of the role of miRNAs in diseases is essential for human health. Here, we have devised a method for comprehensively mapping the associations between miRNAs and diseases by merging on a common key between two curated omics databases. The resulting bidirectional resource, miR2Trait, is more detailed than earlier catalogs, uncovers new relationships, and includes analytical utilities to interrogate and extract knowledge from these datasets. miR2Trait provides resources to compute the disease enrichment of a user-given set of miRNAs and analyze the miRNA profile of a specified diseasome. Reproducible examples demonstrating use-cases for each of these resource components are illustrated. Furthermore we used these tools to construct pairwise miRNA-miRNA and disease-disease enrichment networks, and identified 23 central miRNAs that could underlie major regulatory functions in the human genome. miR2Trait is available as an open-source command-line interface in Python3 (URL: https://github.com/miR2Trait) with a companion wiki documenting the scripts and data resources developed, under MIT license for commercial and non-commercial use. A minimal web-based implementation has been made available at https://sas.sastra.edu/pymir18. Supplementary information is available at: https://doi.org/10.6084/m9.figshare.8288825.v3.

EVs-miRNA: The New Molecular Markers for Chronic Respiratory Diseases.

Idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD), asthma and sleep disorders are chronic respiratory diseases that affect the airways, compromising lung function over time. These diseases affect hundreds of millions of people around the world and their frequency seems to be increasing every year. Extracellular vesicles (EVs) are small-sized vesicles released by every cell in the body. They are present in most body fluids and contain various biomolecules including proteins, lipids, mRNA and non-coding RNA (micro-RNA). The EVs can release their cargo, specifically micro-RNAs (miRNAs), to both neighboring and/or distal cells, playing a fundamental role in cell–cell communication. Recent studies have shown their possible role in the pathogenesis of various chronic respiratory diseases. The expression of miRNAs and, in particular, of miRNAs contained within the extracellular vesicles seems to be a good starting point in order to identify new potential biomarkers of disease, allowing a non-invasive clinical diagnosis. In this review we summarize some studies, present in the literature, about the functions of extracellular vesicles and miRNAs contained in extracellular vesicles in chronic respiratory diseases and we discuss the potential clinical applications of EVs and EVs-miRNAs for their possible use such as future biomarkers.

MicroRNA let-7f-5p regulates PI3K/AKT/COX2 signaling pathway in bacteria-induced pulmonary fibrosis via targeting of PIK3CA in forest musk deer.

BackgroundRecent studies have characterized that microRNA (miRNA) is a suitable candidate for the study of bleomycin/LPS-induced pulmonary fibrosis, but the knowledge on miRNA in bacteria-induced pulmonary fibrosis (BIPF) is limited. Forest musk deer (Moschus berezovskii, FMD) is an important endangered species that has been seriously affected by BIPF. We sought to determine whether miRNA exist that modulates the pathogenesis of BIPF in FMD.MethodsHigh-throughput sequencing and RT-qPCR were used to determine the differentially expressed miRNAs (DEmiRNAs) in the blood of BIPF FMD. The DEmiRNAs were further detected in the blood and lung of BIPF model rat by RT-qPCR, and the targeting relationship between candidate miRNA and its potential target gene was verified by dual-luciferase reporter activity assay. Furthermore, the function of the candidate miRNA was verified in the FMD lung fibroblast cells (FMD-C1).ResultsHere we found that five dead FMD were suffered from BIPF, and six circulating miRNAs (miR-30g, let-7f-5p, miR-27-3p, miR-25-3p, miR-9-5p and miR-652) were differentially expressed in the blood of the BIPF FMD. Of these, let-7f-5p showed reproducibly lower level in the blood and lung of the BIPF model rat, and the expression levels of PI3K/AKT/COX2 signaling pathway genes (PIK3CA, PDK1, Akt1, IKBKA, NF-κB1 and COX2) were increased in the lung of BIPF model rats, suggesting that there is a potential correlation between BIPF and the PI3K/AKT/COX2 signaling pathway. Notably, using bioinformatic prediction and experimental verification, we demonstrated that let-7f-5p is conserved across mammals, and the seed sequence of let-7f-5p displays perfect complementarity with the 3’ UTR of PIK3CA gene and the expression of the PIK3CA gene was regulated by let-7f-5p. In order to determine the regulatory relationship between let-7f-5p and the PI3K/AKT/COX2 signaling pathway in FMD, we successfully cultured FMD-C1, and found that let-7f-5p could act as a negative regulator for the PI3K/Akt/COX2 signaling pathway in FMD-C1. Collectively, this study not only provided a study strategy for non-invasive research in pulmonary disease in rare animals, but also laid a foundation for further research in BIPF.

Identification and characterization of miRNAome and target genes in Pseudostellaria heterophylla.

miRNAs play a crucial role in the development and growth of plants by inhibiting the function of targeted genes at the post-transcription level. However, no miRNAs in Pseudostellaria heterophylla have been reported and their function in the morphogenesis of organs is still unclear. In this study, a total of 159 conserved miRNAs (belonging to 64 families) and 303 level miRNAs were identified from P. heterophylla. Some of them showed specifically up or down-regulated expression in different tissues and numbers of unigenes involved in Plant-pathogen interaction and MAPK signaling pathway-plant were targeted. The significant negative correlation of expression profiles between 30 miRNAs and their target genes (37 unigenes) was observed, respectively. Further, a large number of genes involved with signal transduction of auxin, zeatin, abscisic acid and, jasmonic acid were targeted. Predicated targets of two miRNAs were validated by 5′RLM-RACE, respectively. A large number of mRNAs from four pathogens were targeted by miRNAs from P. heterophylla and some of them were targeted by miR414. In summary, we reported a population of miRNAs from four different vegetative tissues of P. heterophylla by high throughput sequencing, which was analyzed by combining with the constructed transcriptome. These results may help to explain the function of miRNAs in the morphogenesis of organs and defense of pathogens, and may provide theoretical basis for breeding and genetic improvement of P. heterophylla.

Dynamic Analysis of microRNAs from Different Life Stages of Rhipicephalus microplus (Acari: Ixodidae) by High-Throughput Sequencing.

MicroRNAs (miRNAs), which are small, noncoding RNA molecules, play an important regulatory role in gene expression at the posttranscriptional level. Relatively limited knowledge exists on miRNAs in Rhipicephalus microplus ticks in China; however, understanding the physiology of miRNA functions and expression at different developmental stages is important. In this study, three small RNA libraries were constructed for R. microplus eggs, larvae, and female adults; miRNAs were detected during these developmental stages by high-throughput sequencing, with 18,162,337, 8,090,736, and 11,807,326 clean reads, respectively. A total of 5132 known miRNAs and 31 novel miRNAs were identified. A total of 1736 differentially expressed miRNAs were significantly different at a p-value of <0.01; in female adults, 467 microRNAs were upregulated and 376 miRNAs downregulated compared to larval tick controls. Using larvae as controls, 218 upregulated and 203 downregulated miRNAs were detected in eggs; in eggs, 108 miRNAs were upregulated and 364 downregulated compared to female adults controls. To verify the reliability of the sequencing data, RT–qPCR was applied to compare expression levels of novel miRNAs. Some differentially expressed miRNAs are involved in developmental physiology, signal transduction, and cell-extracellular communications based on GO annotation and KEGG pathway analyses. Here, we provide a dynamic analysis of miRNAs in R. microplus and their potential targets, which has significance for understanding the biology of ticks and lays the foundation for improved understanding of miRNA functioning in the regulation of R. microplus development. These results can assist future miRNA studies in other tick species that have great significance for human and animal health.

Role of microRNAs in trophoblast invasion and spiral artery remodeling: Implications for preeclampsia.

It is now well-established that microRNAs (miRNAs) are important regulators of gene expression. The role of miRNAs in placental development and trophoblast function is constantly expanding. Trophoblast invasion and their ability to remodel uterine spiral arteries are essential for proper placental development and successful pregnancy outcome. Many miRNAs are reported to be dysregulated in pregnancy complications, especially preeclampsia and they exert various regulatory effects on trophoblasts. In this review, we provide a brief overview of miRNA biogenesis and their mechanism of action, as well as of trophoblasts differentiation, invasion and spiral artery remodeling. We then discuss the role of miRNAs in trophoblasts invasion and spiral artery remodeling, focusing on miRNAs that have been thoroughly investigated, especially using multiple model systems. We also discuss the potential role of miRNAs in the pathogenesis of preeclampsia.

Crosstalk of miRNAs with signaling networks in bladder cancer progression: Therapeutic, diagnostic and prognostic functions

Urological cancers are considered as life-threatening diseases around the world. Bladder cancer is one of the most malignant urological tumors with high mortality and morbidity. Bladder cancer is a heterogenous disease and genetic alterations have shown to be key players in regulating its progression. Although conventional therapies are somewhat beneficial in improving prognosis and survival, bladder cancer patients suffer from recurrence. MicroRNAs (miRNAs) are endogenous short RNA molecules that do not encode proteins and show dysregulated expression in human cancers. miRNAs are regulators of vital biological processes in cells such as proliferation, migration, differentiation and apoptosis. Dysregulation of miRNAs is observed in bladder cancer and they are used as biomarkers for diagnosis and prognosis of patients. LncRNAs and circRNAs are modulators of bladder cancer progression via miRNA expression regulation. Overexpression of onco-suppressor miRNAs impairs bladder cancer progression, while oncogenic miRNAs drive tumor progression. Glycolysis and EMT mechanisms are two important factors for proliferation and migration of bladder cancer that are modulated by miRNAs. Furthermore, miRNAs can affect STAT3 and Wnt/β-catenin as instances of molecular factors in regulating bladder tumor progression. Bladder tumor response to drug therapy and radiotherapy is regulated by miRNAs. Hence, aim of current review is to provide function of miRNAs in bladder cancer based on their crosstalk with other molecular pathways and interaction with biological processes.

Differentially Expressed mRNAs and Potential Mechanisms of Radiation-Induced TUT4-/- Esophageal Cell Injury.

Radiation-induced esophageal injury remains a limitation for the process of radiotherapy for lung and esophageal cancer patients. Esophageal epithelial cells are extremely sensitive to irradiation, nevertheless, factors involved in the radiosensitivity of esophageal epithelial cells are still unknown. Terminal uridyl transferase 4 (TUT4) could modify the sequence of miRNAs, which affect their regulation on miRNA targets and function. In this study, we used transcriptome sequencing technology to identify mRNAs that were differentially expressed before and after radiotherapy in esophageal epithelial cells. We further explored the mRNA expression profiles between wild-type and TUT4 knockout esophageal epithelial cells. Volcano and heatmap plots unsupervised hierarchical clustering analysis were performed to classify the samples. Enrichment analysis on Gene Ontology functional annotations and Kyoto Encyclopedia of Genes and Genomes pathways was performed. We annotated differential genes from metabolism, genetic information processing, environmental information processing, cellular processes, and organismal systems human diseases. The aberrantly expressed genes are significantly enriched in irradiation-related biological processes, such as DNA replication, ferroptosis, and cell cycle. Moreover, we explored the distribution of transcription factor family and its target genes in differential genes. These mRNAs might serve as therapeutic targets in TUT4-related radiation-induced esophageal injury.