microRNA Function Research Articles

MicroRNA-130b May Induce Cerebral Vasospasm after Subarachnoid Hemorrhage via Modulating Kruppel-like Factor 4.

Recently, the diverse functions of microRNAs (miRNAs) in brain diseases have been demonstrated. We intended to uncover the functional role of microRNA-130b (miR-130b) in cerebral vasospasm (CVS) following subarachnoid hemorrhage (SAH). SAH was induced by injecting the autologous blood into the cisterna magna of Sprague Dawley rats. The cerebral vascular smooth muscle cells (cVSMCs) were extracted for invitro experimentation. In vitro and invivo assays were implemented with transfection of miR-130b mimic/inhibitor, sh-Kruppel-like factor 4 (KLF4), oe-KLF4 plasmids or p38/MAPK signaling pathway agonist (anisomycin), respectively, to elaborate the role of miR-130b in CVS following SAH. Elevated miR-130b and reduced KLF4 were found in SAH patients and rat models of SAH. KLF4 was the target gene of miR-130b. miR-130b promoted the proliferation and migration of cVSMCs through the Inhibition of KLF4. Besides, KLF4 inhibited the proliferation and migration of cVSMCs through blockage of the p38/MAPK pathway. Furthermore, invivo assay confirmed the inhibitory effect of decreased miR-130b in CVS following SAH. In conclusion, miR-130b may activate the p38/MAPK signaling pathway through targeted inhibition of KLF4, thereby contributing to some extent to the development of cerebral vasospasm after SAH.

A Novel Pathway of Functional microRNA Uptake and Mitochondria Delivery.

Extracellular microRNAs (miRNAs) play a critical role in horizontal gene regulation. Uptake of extracellular miRNAs by recipient cells and their intracellular transport, however, remains elusive. Here RNA phase separation is shown as a novel pathway of miRNA uptake. In the presence of serum, synthetic miRNAs rapidly self-assembly into ≈110nm discrete nanoparticles, which enable miRNAs' entry into different cells. Depleting serum cationic proteins prevents the formation of such nanoparticles and thus blocks miRNA uptake. Different from lipofectamine-mediated miRNA transfection in which majority of miRNAs are accumulated in lysosomes of transfected cells, nanoparticles-mediated miRNA uptake predominantly delivers miRNAs into mitochondria in a polyribonucleotide nucleotidyltransferase 1(PNPT1)-dependent manner. Functional assays further show that the internalized miR-21 via miRNA phase separation enhances mitochondrial translation of cytochrome b (CYB), leading to increase in adenosine triphosphate (ATP) and reactive oxygenspecies (ROS) reduction in HEK293T cells. The findings thus reveal a previously unrecognized mechanism for uptake and delivery functional extracellular miRNAs into mitochondria.

Evaluation of MicroRNAs in Pediatric Epilepsy.

The pathophysiology of epilepsy remains unknown. Recent research has shown that microRNA expression changes in epileptic adults. In the present work, we aimed to identify serum microRNA expression in drug-responsive and resistant children with idiopathic general- ized epilepsy. The study included 43 (20 male and 23 female) epilepsy patients and 66 (43 male and 23 female) control subjects. The mean ages of the groups were 113.41 ± 61.83 and 105.46 ± 62.31 months, respectively. Twenty-eight epileptic patients were classi- fied as drug resistant. Thirteen of the controls were the siblings of patients with epilepsy. The study only included children with idiopathic generalized epilepsy who had normal brain mag- netic resonance imaging. The serum microRNA expressions (microRNA-181a, microRNA-155, microRNA-146, and microRNA-223) were investigated. Expressions of serum microRNA-181a, microRNA-155, microRNA-146, and microRNA-223 were previously investigated in epilepsy patients and children with febrile seizures. Therefore, these microRNAs were chosen. The expressions of serum levels of microRNAs were determined using quantitative real-time poly- merase chain reaction. The results indicated that the expressions of serum microRNA-155 and microRNA-223 were elevated in epileptic children (P < .05). The expression of the same microRNAs was also elevated in individuals with drug-resistant epilepsy compared to healthy controls (P < .05). microRNA-146a, microRNA-155, and microRNA-223 expressions were higher in drug-resistant patients than in drug-responsive children (P < .05). A logistic regression study determined that an increase of microRNA-155 was a risk for epilepsy, while a decrease of microRNA-146a risk for epilepsy. Few researchers have investigated the function of microRNAs in the develop- ment of childhood epilepsy. Our findings revealed that epilepsy patients have abnormal microRNAexpression.

Extension of mRNA poly(A) tails and 3'UTRs during neuronal differentiation exhibits variable association with post-transcriptional dynamics.

Differentiation of neural progenitor cells into mature neuronal phenotypes relies on extensive temporospatial coordination of mRNA expression to support the development of functional brain circuitry. Cleavage and polyadenylation of mRNA has tremendous regulatory capacity through the alteration of mRNA stability and modulation of microRNA (miRNA) function, however the extent of utilization in neuronal development is currently unclear. Here, we employed poly(A) tail sequencing, mRNA sequencing, ribosome profiling and small RNA sequencing to explore the functional relationship between mRNA abundance, translation, poly(A) tail length, alternative polyadenylation (APA) and miRNA expression in an in vitro model of neuronal differentiation. Differential analysis revealed a strong bias towards poly(A) tail and 3'UTR lengthening during differentiation, both of which were positively correlated with changes in mRNA abundance, but not translation. Globally, changes in miRNA expression were predominantly associated with mRNA abundance and translation, however several miRNA-mRNA pairings with potential to regulate poly(A) tail length were identified. Furthermore, 3'UTR lengthening was observed to significantly increase the inclusion of non-conserved miRNA binding sites, potentially enhancing the regulatory capacity of these molecules in mature neuronal cells. Together, our findings suggest poly(A) tail length and APA function as part of a rich post-transcriptional regulatory matrix during neuronal differentiation.

A Glance at Biogenesis and Functionality of MicroRNAs and Their Role in the Neuropathogenesis of Parkinson's Disease.

MicroRNAs (miRNAs) are short, noncoding RNA transcripts. Mammalian miRNA coding sequences are located in introns and exons of genes encoding various proteins. As the central nervous system is the largest source of miRNA transcripts in living organisms, miRNA molecules are an integral part of the regulation of epigenetic activity in physiological and pathological processes. Their activity depends on many proteins that act as processors, transporters, and chaperones. Many variants of Parkinson's disease have been directly linked to specific gene mutations which in pathological conditions are cumulated resulting in the progression of neurogenerative changes. These mutations can often coexist with specific miRNA dysregulation. Dysregulation of different extracellular miRNAs has been confirmed in many studies on the PD patients. It seems reasonable to conduct further research on the role of miRNAs in the pathogenesis of Parkinson's disease and their potential use in future therapies and diagnosis of the disease. This review presents the current state of knowledge about the biogenesis and functionality of miRNAs in the human genome and their role in the neuropathogenesis of Parkinson's disease (PD)-one of the most common neurodegenerative disorders. The article also describes the process of miRNA formation which can occur in two ways-the canonical and noncanonical one. However, the main focus was on miRNA's use in in vitro and in vivo studies in the context of pathophysiology, diagnosis, and treatment of PD. Some issues, especially those regarding the usefulness of miRNAs in PD's diagnostics and especially its treatment, require further research. More standardization efforts and clinical trials on miRNAs are needed.

Role of Vitamin D in Head and Neck Cancer-Immune Function, Anti-Tumour Effect, and Its Impact on Patient Prognosis.

Head and neck squamous cell carcinoma (HNSCC) describes a heterogeneous group of human neoplasms of the head and neck with high rates of morbidity and mortality, constituting about 3% of all cancers and ~1.5% of all cancer deaths. HNSCC constituted the seventh most prevalent human malignancy and the most common human cancer in the world in 2020, according to multi-population observations conducted by the GLOBOCAN group. Since approximately 60-70% of patients present with stage III/IV neoplastic disease, HNSCC is still one of the leading causes of death in cancer patients worldwide, with an overall survival rate that is too low, not exceeding 40-60% of these patients. Despite the application of newer surgical techniques and the implementation of modern combined oncological treatment, the disease often follows a fatal course due to frequent nodal metastases and local neoplastic recurrences. The role of micronutrients in the initiation, development, and progression of HNSCC has been the subject of considerable research. Of particular interest has been vitamin D, the pleiotropic biologically active fat-soluble family of secosteroids (vitamin-D-like steroids), which constitutes a key regulator of bone, calcium, and phosphate homeostasis, as well as carcinogenesis and the further development of various neoplasms. Considerable evidence suggests that vitamin D plays a key role in cellular proliferation, angiogenesis, immunity, and cellular metabolism. A number of basic science, clinical, and epidemiological studies indicate that vitamin D has multidirectional biological effects and influences anti-cancer intracellular mechanisms and cancer risk, and that vitamin D dietary supplements have various prophylactic benefits. In the 20th century, it was reported that vitamin D may play various roles in the protection and regulation of normal cellular phenotypes and in cancer prevention and adjunctive therapy in various human neoplasms, including HNSCC, by regulating a number of intracellular mechanisms, including control of tumour cell expansion and differentiation, apoptosis, intercellular interactions, angio- and lymphogenesis, immune function, and tumour invasion. These regulatory properties mainly occur indirectly via epigenetic and transcriptional changes regulating the function of transcription factors, chromatin modifiers, non-coding RNA (ncRNAs), and microRNAs (miRs) through protein-protein interactions and signalling pathways. In this way, calcitriol enhances intercellular communication in cancer biology, restores the connection with the extracellular matrix, and promotes the epithelial phenotype; it thus counteracts the tumour-associated detachment from the extracellular matrix and inhibits the formation of metastases. Furthermore, the confirmation that the vitamin D receptor (VDR) is present in many human tissues confirmed the physiopathological significance of vitamin D in various human tumours. Recent studies indicate quantitative associations between exposure to vitamin D and the incidence of HNC, i.e., cancer risk assessment included circulating calcidiol plasma/serum concentrations, vitamin D intake, the presence of the VDR gene polymorphism, and genes involved in the vitamin D metabolism pathway. Moreover, the chemopreventive efficacy of vitamin D in precancerous lesions of the head and neck and their role as predictors of mortality, survival, and recurrence of head and neck cancer are also widely discussed. As such, it may be considered a promising potential anti-cancer agent for developing innovative methods of targeted therapy. The proposed review discusses in detail the mechanisms regulating the relationship between vitamin D and HNSCC. It also provides an overview of the current literature, including key opinion-forming systematic reviews as well as epidemiological, prospective, longitudinal, cross-sectional, and interventional studies based on in vitro and animal models of HNSCC, all of which are accessible via the PubMed/Medline/EMBASE/Cochrane Library databases. This article presents the data in line with increasing clinical credibility.

A Novel Defined PANoptosis-Related miRNA Signature for Predicting the Prognosis and Immune Characteristics in Clear Cell Renal Cell Carcinoma: A miRNA Signature for the Prognosis of ccRCC.

Clear cell renal cell carcinoma (ccRCC) is one of the most prevalent cancers, and PANoptosis is a distinct, inflammatory-programmed cell death regulated by the PANoptosome. The essential regulators of cancer occurrence and progression are microRNAs (miRNAs). However, the potential function of PANoptosis-related microRNAs (PRMs) in ccRCC remains obscure. This study retrieved ccRCC samples from The Cancer Genome Atlas database and three Gene Expression Omnibus datasets. PRMs were recognized based on previous reports in the scientific literature. Regression analyses were used to identify the prognosis PRMs and construct a PANoptosis-related miRNA prognostic signature based on the risk score. We discovered that high-risk patients had poorer survival prognoses and were significantly linked to high-grade and advanced-stage tumors, using a variety of R software packages and web analysis tools. Furthermore, we demonstrated that the low-risk group had significant changes in their metabolic pathways. In contrast, the high-risk group was characterized by high immune cell infiltration, immune checkpoint expression, and low half-maximum inhibition concentration (IC50) values of chemotherapeutic agents. This suggests that high-risk patients may benefit more from immunotherapy and chemotherapy. In conclusion, we constructed a PANoptosis-related microRNA signature and revealed its potential significance in clinicopathological features and tumor immunity, thereby providing new precise treatment strategies.

Overexpression of microRNA-93-5p and microRNA-374a-5p Suppresses the Osteogenic Differentiation and Mineralization of Human Aortic Valvular Interstitial Cells Through the BMP2/Smad1/5/RUNX2 Signaling Pathway.

Aortic valve calcification commonly occurs in patients with chronic kidney disease (CKD). However, the regulatory functions of microRNAs (miRNAs/miRs) in the osteogenic differentiation of human aortic valvular interstitial cells (hAVICs) in patients with CKD remain largely unknown. This study aimed to explore the functional role and underlying mechanisms of miR-93-5p and miR-374a-5p in the osteogenic differentiation of hAVICs. For this purpose, hAVICs calcification was induced with high-calcium/high-phosphate medium and the expression levels of miR-93-5p and miR-374a-5p were determined using bioinformatics assay. Alizarin red staining, intracellular calcium content, and alkaline phosphatase activity were used to evaluate calcification. The expression levels of bone morphogenetic protein-2 (BMP2), runt-related transcription factor 2 (Runx2), and phosphorylated (p)-Smad1/5 were detected by luciferase reporter assay, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and western blot analysis. The results revealed that the expression levels of miR-93-5p and miR-374a-5p were significantly decreased in hAVICs in response to high-calcium/high-phosphate medium. The overexpression of miR-93-5p and miR-374a-5p effectively suppressed the high-calcium/high-phosphate-induced calcification and osteogenic differentiation makers. Mechanistically, the overexpression of miR-93-5p and miR-374a-5p inhibits osteogenic differentiation by regulating the BMP2/Smad1/5/Runx2 signaling pathway. Taken together, this study indicates that miR-93-5p and miR-374a-5p suppress the osteogenic differentiation of hAVICs associated with calcium-phosphate metabolic dyshomeostasis through the inhibition of the BMP2/Smad1/5/Runx2 signaling pathway.

MicroRNAs involved in the trans-kingdom gene regulation in the interaction of maize kernels and Fusarium verticillioides

Maize ear rot is a widespread disease and the main pathogen is Fusarium verticillioides. Plant microRNAs (miRNAs) have great effects on disease resistance and it has been reported that maize miRNA participates in defense responses in maize ear rot. However, the trans-kingdom regulation of miRNAs between maize and F. verticillioides remains uncharacterized. In this study, the relationship between miRNA-like RNAs (milRNAs) of F. verticillioides and pathogenicity was investigated, followed by sRNA analysis and degradome sequencing of miRNA profiles and the target genes of maize and F. verticillioides after inoculation. It was found that the milRNA biogenesis positively regulated the pathogenicity of F. verticillioides by knocking out the gene FvDicer2-encoded Dicer-like protein in F. verticillioides. Following inoculation with F. verticillioides, 284 known and 6571 novel miRNAs were obtained in maize, including 28 miRNAs differentially expressed at multiple time points. The target genes of maize differentially expressed miRNAs in F. verticillioides mediated multiple pathways, including autophagy and MAPK signaling pathway. Fifty-one novel F. verticillioides milRNAs were predicted to target 333 genes in maize involved in MAPK signaling pathways, plant hormone signaling transduction and plant-pathogen interaction pathways. Additionally, the miR528b-5p in maize targeted the mRNA of FvTTP which encoded a twice transmembrane protein in F. verticillioides. The FvTTP-knockout mutants displayed decreased pathogenicity and reduced synthesis of fumonisins. Thus, by interfering with the translation of FvTTP, the miR528b-5p inhibited F. verticillioides infection. These findings suggested a novel function of miR528 in resisting F. verticillioides infection. The miRNAs identified in this research and their putative target genes can be used to further elucidate the trans-kingdom functions of microRNAs in plant pathogen interaction.

Effect of hypoxia on the expression of microRNA in extracellular vesicles of human umbilical cord stem cells in vitro.

Mesenchymal stem cells (MSCs) derived extracellular vesicles, which have been shown to possess therapeutic effects for many diseases. However, how hypoxic conditions would affect exosomal microRNA expression in human umbilical cord MSCs (hUC-MSCs) is currently not investigated. This study aims to investigate the potential function of in vitro microRNAs of hUC-MSC cultured under normoxic and hypoxic conditions. Extracellular vesicles secreted from hUC-MSCs cultured in normoxic (21% O2) and hypoxic (5% O2) conditions were collected for microRNA identification. Zeta View Laser Scattering and transmission electron microscopy were used to observe the size and morphology of extracellular vesicles. qRT-PCR was performed to measure the expression of related microRNAs. The Gene Ontology and KEGG pathway were used to predict the function of microRNAs. Finally, the effects of hypoxia on the expression of related mRNAs and cellular activity were examined. This study identified 35 upregulated and 8 downregulated microRNAs in the hypoxia group. We performed target genes analysis to explore the potential function of these microRNA upregulated in the hypoxia group. Significant enrichment of the cell proliferation, pluripotency of stem cells, MAPK, Wnt, and adherens junction pathways were observed in the GO and KEGG pathways. Under hypoxic conditions, the expression levels of 7 target genes were lower than that of the normal environment. In conclusion, this study demonstrated for the first time that microRNA expression in extracellular vesicles of human umbilical vein stem cells cultured under hypoxia is different from that under normal conditions, and these microRNAs may be markers for detecting hypoxia.

MiR-147 Represses NDUFA4, Inducing Mitochondrial Dysfunction and Tubular Damage in Cold Storage Kidney Transplantation.

Cold storage-associated transplantation (CST) injury occurs in renal transplant from deceased donors, the main organ source. The pathogenesis of CST injury remains poorly understood, and effective therapies are not available. This study has demonstrated an important role of microRNAs in CST injury and revealed the changes in microRNA expression profiles. Specifically, microRNA-147 (miR-147) is consistently elevated during CST injury in mice and in dysfunctional renal grafts in humans. Mechanistically, NDUFA4 (a key component of mitochondrial respiration complex) is identified as a direct target of miR-147. By repressing NDUFA4, miR-147 induces mitochondrial damage and renal tubular cell death. Blockade of miR-147 and overexpression of NDUFA4 reduce CST injury and improve graft function, unveiling miR-147 and NDUFA4 as new therapeutic targets in kidney transplantation. Kidney injury due to cold storage-associated transplantation (CST) is a major factor determining the outcome of renal transplant, for which the role and regulation of microRNAs remain largely unclear. The kidneys of proximal tubule Dicer (an enzyme for microRNA biogenesis) knockout mice and their wild-type littermates were subjected to CST to determine the function of microRNAs. Small RNA sequencing then profiled microRNA expression in mouse kidneys after CST. Anti-microRNA-147 (miR-147) and miR-147 mimic were used to examine the role of miR-147 in CST injury in mouse and renal tubular cell models. Knockout of Dicer from proximal tubules attenuated CST kidney injury in mice. RNA sequencing identified multiple microRNAs with differential expression in CST kidneys, among which miR-147 was induced consistently in mouse kidney transplants and in dysfunctional human kidney grafts. Anti-miR-147 protected against CST injury in mice and ameliorated mitochondrial dysfunction after ATP depletion injury in renal tubular cells in intro . Mechanistically, miR-147 was shown to target NDUFA4, a key component of the mitochondrial respiration complex. Silencing NDUFA4 aggravated renal tubular cell death, whereas overexpression of NDUFA4 prevented miR-147-induced cell death and mitochondrial dysfunction. Moreover, overexpression of NDUFA4 alleviated CST injury in mice. microRNAs, as a class of molecules, are pathogenic in CST injury and graft dysfunction. Specifically, miR-147 induced during CST represses NDUFA4, leading to mitochondrial damage and renal tubular cell death. These results unveil miR-147 and NDUFA4 as new therapeutic targets in kidney transplantation.

Potential Function of Testicular MicroRNAs in Heat-Stress-Induced Spermatogenesis Disorders.

Spermatogenesis is temperature-dependent, and the increase in testicular temperature seriously affects mammalian spermatogenesis and semen quality. In this study, the testicular heat stress model of mice was made with a 43 °C water bath for 25 min, and the effects of heat stress on semen quality and spermatogenesis-related regulators were analyzed. On the 7th day after heat stress, testis weight shrank to 68.45% and sperm density dropped to 33.20%. High-throughput sequencing analysis showed that 98 microRNAs (miRNAs) and 369 mRNAs were down-regulated, while 77 miRNAs and 1424 mRNAs were up-regulated after heat stress. Through gene ontology (GO) analysis of differentially expressed genes and miRNA-mRNA co-expression networks, it was found that heat stress may be involved in the regulation of testicular atrophy and spermatogenesis disorders by affecting cell meiosis process and cell cycle. In addition, through functional enrichment analysis, co-expression regulatory network, correlation analysis and in vitro experiment, it was found that miR-143-3p may be a representative potential key regulatory factor affecting spermatogenesis under heat stress. In summary, our results enrich the understanding of miRNAs in testicular heat stress and provide a reference for the prevention and treatment of heat-stress-induced spermatogenesis disorders.

MiEAA 2023: updates, new functional microRNA sets and improved enrichment visualizations.

MicroRNAs (miRNAs) are small non-coding RNAs that play a critical role in regulating diverse biological processes. Extracting functional insights from a list of miRNAs is challenging, as each miRNA can potentially interact with hundreds of genes. To address this challenge, we developed miEAA, a flexible and comprehensive miRNA enrichment analysis tool based on direct and indirect miRNA annotation. The latest release of miEAA includes a data warehouse of 19 miRNA repositories, covering 10 different organisms and 139 399 functional categories. We have added information on the cellular context of miRNAs, isomiRs, and high-confidence miRNAs to improve the accuracy of the results. We have also improved the representation of aggregated results, including interactive Upset plots to aid users in understanding the interaction among enriched terms or categories. Finally, we demonstrate the functionality of miEAA in the context of ageing and highlight the importance of carefully considering the miRNA input list. MiEAA is free to use and publicly available at https://www.ccb.uni-saarland.de/mieaa/.

Host-targeted self-attenuated influenza virus as an effective nasal spray vaccine in aged population

Abstract The elderly are at high risk for influenza infection and its complication. However, current inactivated influenza vaccines are often modestly immunogenic and show low protective immunity in the elderly, due to immunosenescence. New approaches are urgently needed for developing effective vaccines against influenza for the elderly. In current study, we have constructed new recombinant influenza viruses, named host-targeted self-attenuated influenza viruses (SAIVs), which can express functional mammalian species-specific artificial microRNAs (amiRNAs). The expression of these amiRNAs can inhibit expression of some host factors critical for influenza replication, and therefore the resultant recombinant influenza viruses are replication restricted and attenuated in the host cells. One of these SAIVs, which can express an amiRNA that inhibits expression of the host cellular Cdc2-like kinase 1 (CLK1), was produced in embryonic chicken eggs and evaluated in an aged mouse model of influenza infection. It elicited robust antibody and T cell responses against influenza virus and demonstrated significantly protective efficacy against lethal infection with wild type influenza virus H1N1 PR8 after single dose of intranasal vaccination. Our research finding provided a proof of concept that the new host targeted self-attenuated influenza virus can be further used as an effective vaccine against influenza in aged population. Supported by a research grant from National Institute of Allergy and Infectious Diseases (AI133207).

Critical Considerations for Investigating MicroRNAs during Tumorigenesis: A Case Study in Conceptual and Contextual Nuances of miR-211-5p in Melanoma.

MicroRNAs are non-coding RNAs fundamental to metazoan development and disease. Although the aberrant regulation of microRNAs during mammalian tumorigenesis is well established, investigations into the contributions of individual microRNAs are wrought with conflicting observations. The underlying cause of these inconsistencies is often attributed to context-specific functions of microRNAs. We propose that consideration of both context-specific factors, as well as underappreciated fundamental concepts of microRNA biology, will permit a more harmonious interpretation of ostensibly diverging data. We discuss the theory that the biological function of microRNAs is to confer robustness to specific cell states. Through this lens, we then consider the role of miR-211-5p in melanoma progression. Using literature review and meta-analyses, we demonstrate how a deep understating of domain-specific contexts is critical for moving toward a concordant understanding of miR-211-5p and other microRNAs in cancer biology.

Modulation of Ferroptosis by microRNAs in Human Cancer.

Ferroptosis is a cell death pathway triggered by an imbalance between the production of oxidants and antioxidants, which plays an emerging role in tumorigenesis. It is mainly regulated at three different levels including iron metabolism, the antioxidant response, and lipid metabolism. Epigenetic dysregulation is a "hallmark" of human cancer, with nearly half of all human cancers harboring mutations in epigenetic regulators such as microRNA. While being the crucial player in controlling gene expression at the mRNA level, microRNAs have recently been shown to modulate cancer growth and development via the ferroptosis pathway. In this scenario, some miRNAs have a function in upregulating, while others play a role in inhibiting ferroptosis activity. The investigation of validated targets using the miRBase, miRTarBase, and miRecords platforms identified 13 genes that appeared enriched for iron metabolism, lipid peroxidation, and antioxidant defense; all are recognized contributors of tumoral suppression or progression phenotypes. This review summarizes and discuss the mechanism by which ferroptosis is initiated through an imbalance in the three pathways, the potential function of microRNAs in the control of this process, and a description of the treatments that have been shown to have an impact on the ferroptosis in cancer along with potential novel effects.

MiRNA Profiling of Developing Rat Retina in the First Three Postnatal Weeks

The morphogenesis of the mammalian retina depends on the precise control of gene expression during development. Small non-coding RNAs, including microRNAs play profound roles in various physiological and pathological processes via gene expression regulation. A systematic analysis of the expression profile of small non-coding RNAs in developing Wistar rat retinas (postnatally day 5 (P5), P7, P10, P15 and P21) was executed using IonTorrent PGM next-generation sequencing technique to reveal the crucial players in the early postnatal retinogenesis. Our analysis reveals extensive regulatory potential of microRNAs during retinal development. We found a group of microRNAs that show constant high abundance (miR-19, miR-101; miR-181, miR-183, miR-124 and let-7) during the development process. Others are present only in the early stages (miR-20a, miR-206, miR-133, miR-466, miR-1247, miR-3582), or at later stages (miR-29, miR-96, miR-125, miR-344 or miR-664). Further miRNAs were detected which are differentially expressed in time. Finally, pathway enrichment analysis has revealed 850 predicted target genes that mainly participate in lipid-, amino acid- and glycan metabolisms in the examined time-period (P5–P21). P5–P7 transition revealed the importance of miRNAs in glutamatergic synapse and gap junction pathways. Significantly downregulated miRNAs rno-miR-30c1 and 2, rno-miR-205 and rno-miR-503 were detected to target Prkx (ENSRNOG00000003696), Adcy6 (ENSRNOG00000011587), Gnai3 (ENSRNOG00000019465) and Gja1 (ENSRNOG00000000805) genes. The dataset described here will be a valuable resource for clarifying new regulatory mechanisms for retinal development and will greatly contribute to our understanding of the divergence and function of microRNAs.

Bone marrow mesenchymal stem cells derived exosomal miRNAs can modulate diabetic bone-fat imbalance.

Diabetes mellitus is a chronic metabolic disease with systemic complications. Patient with diabetes have increased risks of bone fracture. Previous studies report that diabetes could affect bone metabolism, however, the underlying mechanism is still unclear. We isolated exosomes secreted by bone marrow mesenchymal stem cells of normal and diabetic mice and test their effects on osteogenesis and adipogenesis. Then we screened the differential microRNAs by high-throughput sequencing and explored the function of key microRNA in vitro and in vivo. We find that lower bone mass and higher marrow fat accumulation, also called bone-fat imbalance, exists in diabetic mouse model. Exosomes secreted by normal bone marrow mesenchymal stem cells (BMSCs-Exos) enhanced osteogenesis and suppressed adipogenesis, while these effects were diminished in diabetic BMSCs-Exos. miR-221, as one of the highly expressed miRNAs within diabetic BMSCs-Exos, showed abilities of suppressing osteogenesis and promoting adipogenesis both in vitro and in vivo. Elevation of miR-221 level in normal BMSCs-Exos impairs the ability of regulating osteogenesis and adipogenesis. Intriguingly, using the aptamer delivery system, delivery normal BMSCs-Exos specifically to BMSCs increased bone mass, reduced marrow fat accumulation, and promoted bone regeneration in diabetic mice. We demonstrate that BMSCs derived exosomal miR-221 is a key regulator of diabetic osteoporosis, which may represent a potential therapeutic target for diabetes-related skeletal disorders.

Genetic regulation of nitrogen use efficiency in Gossypium spp.

Cotton (Gossypium spp.) is the most important fibre crop, with desirable characteristics preferred for textile production. Cotton fibre output relies heavily on nitrate as the most important source of inorganic nitrogen (N). However, nitrogen dynamics in extreme environments limit plant growth and lead to yield loss and pollution. Therefore, nitrogen use efficiency (NUE), which involves the utilisation of the 'right rate', 'right source', 'right time', and 'right place' (4Rs), is key for efficient N management. Recent omics techniques have genetically improved NUE in crops. We herein highlight the mechanisms of N uptake and assimilation in the vegetative and reproductive branches of the cotton plant while considering the known and unknown regulatory factors. The phylogenetic relationships among N transporters in four Gossypium spp. have been reviewed. Further, the N regulatory genes that participate in xylem transport and phloem loading are also discussed. In addition, the functions of microRNAs and transcription factors in modulating the expression of target N regulatory genes are highlighted. Overall, this review provides a detailed perspective on the complex N regulatory mechanism in cotton, which would accelerate the research toward improving NUE in crops.

Activity‐Based Protein Profiling – Celebrating the Groundbreaking Contributions of Benjamin Cravatt

Activity‐Based Protein Profiling – Celebrating the Groundbreaking Contributions of Benjamin Cravatt