miRNA Expression Profiles Research Articles

Expression profiling of circular RNAs in sepsis-induced acute gastrointestinal injury: insights into potential biomarkers and mechanisms

This study aimed to investigate the role of circular RNAs (circRNAs) in sepsis-induced acute gastrointestinal injury (AGI), focusing on their potential as biomarkers and their involvement in disease progression. Peripheral blood samples from 14 patients with sepsis-induced AGI and healthy volunteers were collected. RNA sequencing was performed to profile circRNA and miRNA expression. Differential expression analysis identified key regulatory RNAs. Functional enrichment analysis was conducted to explore biological pathways, and circRNA-miRNA interaction networks were constructed. Significant differences in circRNA and miRNA expression profiles were observed between sepsis-induced AGI patients and healthy controls. Several circRNAs, including hsa_circ_0008381 and hsa_circ_0071375, exhibited stepwise expression increases correlating with AGI severity. Functional enrichment analysis indicated that the host genes of differentially expressed circRNAs are involved in key biological processes like protein ubiquitination, organelle maintenance, and cellular signaling pathways such as mitochondrial biogenesis and lipid metabolism. CircRNA-miRNA interaction networks suggested their role as miRNA sponges, regulating key downstream processes. This study demonstrated the potential of circRNAs as diagnostic biomarkers and therapeutic targets for sepsis-induced AGI. Further research is warranted to validate their clinical utility and unravel their mechanistic roles in AGI progression.

MiR-224 activates cancer-associated fibroblasts to enhance lung cancer cell migration and invasion by targeting Akirin1

Cancer-associated fibroblasts (CAFs) actively contribute to the formation of tumor-supportive microenvironments, thereby promoting cancer progression and impacting therapeutic outcomes. This study utilized global microRNA (miRNA) expression profiling to identify specific miRNAs responsible for reprogramming normal lung fibroblasts (LFs) into CAFs. miR-224 demonstrates increased expression in CAFs, and its levels are elevated in lung tumors compared to those in normal tissues, according to data from public databases. Overexpression of miR-224 in LFs increases the overall expression of CAF activation markers. Furthermore, LFs overexpressing miR-224 enhanced the migration and invasion of lung cancer cells via direct cell-to-cell contact in a co-culture system. In a mouse orthotopic injection model, miR-224 overexpression in LFs increased lung cancer metastasis. Using target prediction tools and subsequent 3′-UTR luciferase assay, Akirin1 was validated as a direct target gene of miR-224. In addition, LFs depleted of Akirin1 by siRNAs stimulated the migration and invasion of lung cancer cells compared to control LFs. Overall, these findings indicate that miR-224 induces CAF activation and promotes the migration and invasion of lung cancer cells by targeting Akirin1 in co-culture systems.

P1299 Modulation of miR-31-5p expression in patients with Ulcerative Colitis treated with infliximab

Abstract Background Biological therapy has revolutionized the treatment of Ulcerative Colitis (UC), but biomarkers that predict response are still lacking. MicroRNAs (miRNAs) are small non-coding RNA molecules that participate in cellular processes such as proliferation, differentiation, migration, maturation and apoptosis, and therefore are related to immune regulation in physiological and pathological conditions such as Inflammatory Bowel Diseases. Therefore, the objective of the study is to investigate the expression profile of miRNAs in responding and non-responding patients treated with Infliximab and to identify a profile of miRNAs that predict therapeutic response. Methods Twelve miRNAs: miR-21-5p, miR-31-5p, miR-192-3p, miR-192-5p, miR-215-5p, miR-326, miR-378-3p, miR-378-5p, miR-422a, miR-429, miR-551a and miR-1258-3p were evaluated in naïve patients with UC before and after treatment with Infliximab (week 54). MiRNA was extracted from formalin-fixed, paraffin-embedded (FFPE) colon tissue and qRT-PCR was performed from 12 patients, of which: 5 responding and 7 non-responding, both groups evaluated pre and post treatment (n=24 samples). Results Decreased expression was found for miR-31-5p (p=0.03) when comparing responding patients pre and post treatment, meanwhile miR-192-5p (p > 0.99) and miR-378-3p (p > 0.99) were suggestive but not statistically different. The other miRNAs had not had expressive results. Conclusion Infliximab-responding patients with UC presented decreased expression of miR-31-5p. MiR-31-5p regulates IL-25 and activates Th1/Th17 mediated inflammation in UC. Therefore, our results reinforce the importance of miR-31-5p expression in UC and indicate a relationship between this miRNA and the effectiveness of the treatment.

Altered expression of miRNA profile in peripheral blood mononuclear cells following the third dose of inactivated COVID-19 vaccine.

COVID-19 vaccination is the most effective strategy for preventing severe disease and death. Inactivated vaccines are the most accessible type of COVID-19 vaccines in developing countries. Several studies, including work from our group, have demonstrated that the third dose (booster vaccination) of inactivated COVID-19 vaccine induces robust humoral and cellular immune responses. The present study aimed to examine miRNA expression profile in participants who received a homologous third dose of the CoronaVac vaccine. Samples of peripheral blood mononuclear cells (PBMCs) were collected from healthcare volunteers both before and 1-2 weeks after the booster dose. miRNA microarray analysis in a discovery cohort of six volunteers identified 67 miRNAs with differential expression. Subsequently, the expression of six miRNAs related to immune responses was examined in a validation cohort of 31 participants via qRT-PCR. Our results validated the differential expression of miR-25-5p, miR-34c-3p, and miR-206 post-booster, with a significant correlation to the receptor binding domain (RBD)-specific antibody. Bioinformatic analysis suggested that miR-25-5p, miR-34c-3p, and miR-206 may target multiple pathways involved in immune regulation and inflammation. Therefore, our study highlights miR-25-5p, miR-34c-3p, and miR-206 in PBMCs as promising biomarkers for assessing the immune response induced by the booster dose of the CoronaVac vaccine.

Identification of puberty related miRNAs in the hypothalamus of female mice.

Puberty is a crucial developmental stage marked by the transition from childhood to adulthood, organized by complex hormonal signaling within the neuroendocrine system. The hypothalamus, a central region in this system, regulates pubertal functions through the hypothalamic-pituitary-gonadal (HPG) axis. Gonadotropin-releasing hormone (GnRH) neurons, essential in puberty control, release GnRH in a pulsatile manner, initiating the production of sex hormones. Major influence in pubertal timing has been attributed to genetic predisposition, environmental factors, and nutritional status. MicroRNAs (miRNAs), small non-coding RNA molecules, have emerged as key regulators in various cellular processes by either repressing genes or activating them by inhibiting their repressors. The present study aims to investigate the involvement of miRNAs in the control of puberty. Small RNA sequencing was used to identify and compare the total population of miRNAs in the hypothalamus of female mice before, during and after puberty. Bioinformatic analysis was applied to analyse the expression profile of miRNAs with altered levels followed by pathway enrichment analysis. Expression levels of several miRNAs were found up- or down-regulated from pre-pubertal to pubertal stage. Furthermore, monitoring the levels of these miRNAs at the post-pubertal stage revealed four expression patterns, in which pathway analysis displayed the associations of these miRNAs with developmental processes, cell cycle regulation, metabolic biosynthesis and epigenetic regulation. The findings of the present study improve our understanding of the molecular pathways underlying puberty and stress the significance of miRNAs in fine-tuning gene expression within the hypothalamus during this critical developmental stage.

Expression Profile of MicroRNAs in Breast Milk of Women With Inflammatory Bowel Disease: Correlation With Disease Activity and Medical Treatments.

Although most inflammatory bowel disease (IBD) medications are considered safe during pregnancy, their impact on microRNAs (miRNAs) in breast milk is largely unknown. MiRNAs in milk, carried by milk-derived extracellular vesicles (MDEs), are transmitted to the newborn's gut to regulate genes. Aberrant miRNA expression profiles have been found in IBD within tissue, blood, and feces, but data on mother's milk are scarce. We collected breast milk samples from 32 mothers with Crohn's disease (CD), 14 mothers with ulcerative colitis (UC), and 44 healthy controls. We analyzed miRNA expression through qualitative real-time polymerase chain reaction and Affymetrix miRNA chips. Target genes of differentially expressed miRNAs were predicted using miRATBase. Statistical analyses were conducted using GraphPad Prism software with Mann-Whitney tests. Milk-derived extracellular vesicles from mothers with IBD showed altered miRNA profiles compared to controls. Specifically, miR-21 and miR-320 were downregulated, while Let-7a was upregulated in IBD mothers. The expression patterns varied between CD and UC, with significantly lower MiR-21 in UC and higher Let-7a in CD. Additionally, anti-tumor necrosis factor treatment during pregnancy was associated with reduced miR-21 and miR-148a levels in MDEs. Pathway analysis revealed that these miRNAs are involved in immune regulation, particularly interleukin signaling pathways. This study highlights that miRNAs in breast milk are differentially expressed in mothers with IBD, influenced by the disease and its treatments. These findings emphasize the impact of maternal health on milk composition and potential implications for infant immune development. Understanding these findings may guide personalized treatment strategies for mothers and promote breastfeeding among mothers with IBD.

Exploring the regulatory role of small RNAs in modulating host-pathogen interactions: implications for bacterial and viral infections.

MicroRNAs (miRNAs) and transfer RNA-derived stress-induced RNAs (tiRNAs) have emerged as crucial players in the post-transcriptional regulation of gene expression in various cellular processes, including immunity and host defense against infections. In recent years, increasing evidence has highlighted their complex role in influencing the host response during viral and bacterial infections. miRNAs have been shown to play multiple roles in host-pathogen interaction like TLR activation and altered disease virulence during bacterial infections. In the context of viral infections, miRNAs are involved in regulating viral replication, pathogenesis, and immune evasion. Similarly, tiRNAs have recently emerged as novel players in bacterial and viral infections such as modulating bacterial growth, adaptation to stress conditions, host antiviral responses, and impacting viral replication and pathogenesis. This review provides a comprehensive analysis of the potential of miRNA expression profiles as diagnostic biomarkers to differentiate between bacterial and viral infections. Further discusses the key pathways through which small RNAs regulate bacterial and viral infection-related diseases.

MicroRNAs Expression Profile in MN1-Altered Astroblastoma.

Astroblastoma is a rare glial neoplasm more frequent in young female patients, with unclear clinical behaviors and outcomes. The diagnostic molecular alteration is a rearrangement of the Meningioma 1 (MN1) gene. MicroRNAs (miRNAs) are important gene expression regulators with strong implications in biological processes. Here, we investigated microRNA expression, regulation, and biological processes correlated to target genes of deregulated miRNAs in MN1-altered astroblastoma. A cohort of 14 tumor samples, histologically classified as astroblastoma, was retrospectively collected and analyzed through their DNA methylation profiles. MiRNA expression profiles were then detected on MN1-altered astroblastomas (n = 8) and normal brain controls (n = 2) by Nanostring technology and validated by RT-qPCR; then, the expression of deregulated miRNAs was correlated with clinical-pathological characteristics. Subsequently, the methylation status of promoters of deregulated miRNAs was investigated through a methylation profiling microarray. Finally, bioinformatics analysis was conducted to explore the biological processes (BPs) and target genes of differentially expressed miRNAs. Eight MN-altered astroblastoma were identified. Thirty-nine miRNAs were deregulated in tumor samples compared to normal brain tissue. Downregulated microRNAs exhibited an association with an increased risk of recurrence. The promoter methylation status was investigated in 32/39 miRNAs: 14/32 were epigenetically deregulated. None of them were genetically regulated. MN1-altered astroblastomas have an miRNA expression signature that identifies specific BPs and pathways. Our findings suggested that the involved pathways could be associated with clinical and pathological characteristics of MN1-altered astroblastomas. Also, the biology of this rare tumor could have potential implications on prognostic markers and therapy.

MiRNA Expression Profile in Primary Limbal Epithelial Cells of Aniridia Patients.

This study evaluates the microRNA (miRNA) expression profile in primary limbal epithelial cells (pLECs) of patients with aniridia. Primary human LECs were sampled and isolated from 10 patients with aniridia and 10 healthy donors. The miRNA profile was analyzed using miRNA microarrays. The biological roles of miRNA-validated target genes were delineated in silico by the enrichment analyses of the gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The expression of the most deregulated miRNAs was analyzed using quantitative real-time PCR (qRT-PCR). Microarray analysis revealed 10 differentially expressed miRNAs in pLECs of patients with aniridia relative to healthy controls (fold change = ≤ -2 or ≥ +2), nevertheless these were only differentially expressed using an unadjusted P value < 0.05. The qRT-PCR validation confirmed the significantly altered expression of miR-138-5p in pLECs of patients with aniridia (P = 0.005). In silico GO analysis of miR-138-5p target genes revealed the potential biological functions of miR-138-5p in regulating various cellular and molecular processes, including the positive regulation of cell motility, G1/S phase cell cycle transition, and cell migration, as well as the negative role in regulating epithelial cell differentiation. Pathway analysis highlighted the main involvement of the PI3K-Akt, Hippo, Wnt, Focal adhesion, cAMP, p53, IL-17, Jak-STAT, and MAPK-signaling pathways. This study revealed miRNA expression profile in pLECs of patients with aniridia using miRNA microarray and identified miRNAs that had not been previously reported for aniridia LECs. Our study also provides functional and pathway information that can be used to predict possible mechanism of miRNA function in LECs, thereby bridging the gap in the pathogenesis of AAK studies.

Comparative Analysis of miRNA Expression Profiles of Yak Milk-Derived Exosomes at Different Altitudes.

Yaks are a rare and unique animal species inhabiting the Qinghai-Tibet Plateau; they are renowned for their remarkable ability to thrive in harsh environments. Milk-derived exosomes, tiny vesicles containing various biological molecules, play crucial roles in numerous pathological and physiological processes, including cell growth, development, and immune regulation. This study delved into the microRNA expression profiles of yak milk-derived exosomes collected from both high- and low-altitude populations using small RNA sequencing. These miRNAs were found to be implicated in pathways associated with mammary gland inflammation, virus infection regulation, and heat stress response. Functional enrichment analyses, utilizing GO and KEGG databases, revealed that the target genes of these differentially expressed miRNAs are enriched in signaling pathways crucial for Th17 cell differentiation and the Ras-MAPK signaling pathway. In conclusion, this research illuminates the adaptive mechanisms of yaks through the differential expression of miRNAs in their milk-derived exosomes across varying environmental conditions. These findings provide a valuable foundation for future investigations into yak resilience and the potential of milk-derived exosomes as tools for disease management and immune modulation.

Analysis of Exosomal miRNA and Hepatic mRNA Expression in the Dysregulation of Insulin Action in Perimenopausal Mice.

Introduction: The aim of present study was to evaluate the impact of perimenopause on insulin resistance. Specifically, insulin sensitivity was assessed in a perimenopausal mouse model treated with 4-vinylcyclohexene diepoxide (VCD), together with the changes in exosomal miRNA and hepatic mRNA expression profiles. Methods: Homeostasis model assessment of insulin resistance (HOMA-IR) was utilized to assess the status of insulin resistance, and insulin action was evaluated during menopausal transition. RNA sequencing (RNA-seq) analysis was used to identify altered expression profiles of exosomal miRNAs and hepatic mRNAs. Differentially expressed miRNA (DEM)-differentially expressed gene (DEG) network analyses were also conducted. Furthermore, altered expression levels of these exosomal miRNAs and genes were validated in plasma exosomes and liver tissue of perimenopausal mice. Results: HOMA-IR in VCD-treated mice was significantly increased, and hepatic glycogen was significantly decreased. Key exosomal miRNAs (miR-17-3p, miR-134-5p, miR-700-5p, and miR-6899-3p) and hepatic genes (G6pdx, Ptpn2, Lepr, Kras, and Braf) may be associated with impaired insulin signaling during perimenopause. Conclusion: The perimenopausal period acts as a potential factor in introducing insulin resistance as evidenced by impaired insulin action and altered expression profiles of exosomal miRNAs and hepatic genes. The present study contributes to the understanding that abnormal cargos carried by plasma exosomes, such as miRNAs, may be related to altered expression of the corresponding genes in the liver and abnormal insulin response.

MicroRNA Expression in High-Grade B-Cell Lymphoma With 11q Aberration.

Mature aggressive B-cell lymphomas, such as Burkitt lymphoma (BL) and Diffuse large B-cell lymphoma (DLBCL), show variations in microRNA (miRNA) expression. The entity of High-grade B-cell lymphoma with 11q aberration (HGBCL-11q) shares several biological features with both BL and DLBCL but data on its miRNA expression profile are yet scarce. Hence, this study aims to analyze the potential differences in miRNA expression of HGBCL-11q compared to BL and DLBCL. We evaluated the expression profiles of 2083 miRNAs in 25 HGCBL-11q, 7 BL, 131 DLBCL, and tonsils using the HTG EdgeSeq miRNA whole transcriptome assay. Uniform manifold approximation and projection (UMAP) and differential gene expression analyses based on DESeq2 were carried out. UMAP analysis of miRNA expression did not reveal distinct groups among the studied lymphomas. However, differential gene expression investigations detected sets of overexpressed miRNAs in HGBCL-11q when compared to BL (miR-9-3p, miR-9-5p, miR-3919, miR-129-1-3p, miR-129-2-3p, miR-331-3p, miR-196b-5p, and miR-28-5p) and DLBCL (miR-3919, miR-1290, miR-4538, and miR-4791), respectively. Notably, miR-3919 showed heterogeneous but significantly higher expression (p-value < 0.001) in HGBCL-11q than in both, BL and DLBCL. We identified a group of differentially expressed miRNAs between HGBCL-11q vs. BL and DLBCL, with miR-3919 as the most commonly and recurrently overexpressed miRNA in HGBCL-11q.

Integrated analysis of miRNA and mRNA expression profiles in the bursa of Fabricius of specific pathogen-free chickens infected with avian reticuloendotheliosis virus strain SNV.

Reticuloendotheliosis virus (REV) is a gamma retrovirus that can cause immunosuppression, dwarf syndrome and acute reticulocytoma in poultry. The molecular mechanism by which REV infection leads to immunosuppression and tumorigenesis is poorly understood. In this study, we elucidated the regulatory network of miRNA-mRNA and the major signaling pathways involved in REV-SNV infection. Therefore, we used the spleen necrosis virus (SNV) model of REV to inoculate one-day-old specific pathogen-free (SPF) chickens and then performed global miRNA and mRNA expression profiling by conducting high-throughput sequencing of 18 bursa of Fabricius samples collected at 7, 14, and 21 dpi. In total, 213 differentially expressed miRNAs (DEMs) and 3311 differentially expressed genes (DEGs) were identified. In the miRNA-mRNA network constructed based on the association analysis of these DEMs and DEGs, 1376 negatively correlated miRNA-mRNA pairs were identified; among them, 82 pairs were identified at 7 dpi, 203 pairs were identified at 14 dpi, and 873 pairs were identified at 21 dpi. Moreover, the results of the Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis of the mRNAs in the network revealed greater enrichment of immune-related pathways, such as the immune system, signal transduction, cell growth and death, and signaling molecules and interactions. We confirmed the selected immune-related DEMs and their DEGs by conducting quantitative RT-PCR (qRT-PCR) analysis. These findings increased our understanding of the interactions of miRNAs and their target genes during infection with REV-SNV, and contributed to the understanding of host-virus interactions.

The miRNA-mRNA Regulatory Network in Human Hepatocellular Carcinoma by Transcriptomic Analysis From GEO.

Bioinformatics analysis of hepatocellular carcinoma (HCC) expression profiles can aid in understanding its molecular mechanisms and identifying new targets for diagnosis and treatment. In this study, we analyzed expression profile datasets and miRNA expression profiles related to HCC from the GEO using R software to detect differentially expressed genes (DEGs) and differentially expressed miRNAs (DEmiRs). Common DEGs were identified, and a PPI network was constructed using the STRING database and Cytoscape software to identify hub genes. The reduced levels of tumor suppressor miRNAs or down regulated DEmiRs may be increased levels of oncogenes, the oncomirs or up regulated DEmiRs may be decreased levels of tumor suppressor genes in cancerous cells. According to this strategy, increased and decreased DEGs, also increased and decreased DEmiRs were selected. The multimir package was employed to predict target genes for DEmiRs then DEmiRs-hub gene network created. We identified approximately 1000 overlapping DEGs and 60 DEmiRs. Hub genes included RRM2, MELK, KIF11, KIF23, NCAPG, DLGAP5, BUB1B, AURKB, CCNB1, KIF20A, CCNA2, TTK, PBK, TOP2A, CDK1, MAD2L1, BIRC5, ASPM, CDCA8, and CENPF, all associated with significantly worse survival in HCC. miR-224, miR-24, miR-182, miRNA-1-3p, miR-30a, miR-27a, and miR-214 were identified as important DEmiRs with targeting more than six hub genes. Generally, our findings offer insight into the interaction of hub genes and miRNAs in the development of HCC by bioinformatics analysis, information that may prove useful in identifying biomarkers and therapeutic targets in HCC.

A Practical Guideline for MicroRNA Sequencing Data Analysis in Chronic Lymphocytic Leukemia.

MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression. They have been associated with several diseases and cancers, including chronic lymphocytic leukemia (CLL). CLL is the most common form of adult leukemia, and its pathogenesis is driven by the deletion of miRNAs, such as the miR-15a/16-1 cluster. In addition to initiating the development of CLL, the function of miRNAs in regulating the progression of this tumor remains to be investigated. Here, we present a computational pipeline, from the processing of miRNA sequencing files to functional analysis, including differential gene expression and gene set enrichment analysis.We exemplified the utility of the pipeline by applying it to genome-wide small RNA sequencing data from a cohort of CLL patients. The analysis revealed dysregulated expression profiles of miRNAs in CLL. The target genes of these miRNAs are not only associated with the response of CLL patients to current therapies but also involved in several cancer hallmarks, including the avoidance of cell death, the deregulation of cellular energetics, the activation of invasion and metastasis, and genome instability. The identified miRNA-gene interactions offer valuable insights for developing targeted therapies for CLL. In addition, we underscored the importance of a practical and robust computational pipeline to ensure the reliability and reproducibility of miRNA sequencing data analysis.

Unraveling the mechanism of microRNA-134 in colon cancer progression: Targeting KRAS and PIK3CA for cell cycle control and histone deacetylase regulation.

Colon cancer is the leading cause of cancer-related deaths worldwide. MicroRNAs (miRNAs) are key regulators of gene expression, often dysregulated in colon cancer. This study aims to elucidate the therapeutic role of miR-134-5p as a tumor suppressor miRNA in colon cancer cells. We analyzed miRNA expression profiles in primary and metastatic colon cancer cells. The clinical significance of miR-134-5p was evaluated using the TCGA database. Bioinformatics tools (HADDOCK) predicted miRNA-mRNA interactions and the molecular docking of miRNA-mRNA-AGO2 complexes. Luciferase reporter assays, cell proliferation, immunofluorescence, colony forming unit assays, and qRT-PCR analysis assessed miR-134-5p effects on KRAS, PIK3CA, and downstream signaling pathways in primary and metastatic colon cancer cells. miR-134-5p was downregulated in colon cancer cells. Bioinformatics analysis suggested KRAS, PIK3CA, EGFR, and HDAC5 as potential targets. HADDOCK analysis revealed strong binding affinity and structural stability between KRAS, PIK3CA, miR-134-5p, and AGO2. Gene-reporter assays confirmed miR-134-5p-mediated degradation of KRAS and PIK3CA. miR-134-5p transfection reduced KRAS and PI3K protein levels, suppressed EGFR/RTK signaling and its downstream targets, and inhibited HDAC expression, ultimately reducing colon cancer cell proliferation. The results of this study confirm that miR-134-5p acts as a potential tumor suppressor miRNA in colon cancer cells by inhibiting KRAS and PI3K expression through AGO2-mediated gene silencing. It deregulates downstream EGFR signaling and HDACs, thereby reducing colon cancer cell proliferation. These findings highlight miR-134-5p as a promising therapeutic target for miRNA-mediated anticancer therapy.

Response of miRNA to treatment with Hypericum perforatum L. oil in multiple sclerosis.

MicroRNA‑regulated gene expression plays an important role in autoimmune diseases, such as multiple sclerosis (MS). This study investigated the expression patterns of microRNAs (miRNAs) in MS in brain tissues using an animal experimental autoimmune encephalomyelitis (EAE) model treated with Hypericum perforatum (HP) oil. C57BL/6 J mice were divided into two groups: MS and control. The MS group was subdivided into sham (MS) and MS+HP. After the EAE induction treatment protocol, the patterns of miRNA expression profiles were determined in brain samples of the groups. The array data identified eleven miRNAs and candidate miRNA validation was performed by RT‑qPCR. A literature review of the validated miRNAs found that six of the eleven miRNAs (miR‑200a‑3p, miR‑200b‑3p, miR‑200c‑3p, miR‑182‑5p, miR‑183‑5p, and miR‑1298‑5p) were directly associated with MS. These miRNAs have been suggested as biomarkers of MS because they are highly correlated with the pathology of the disease. Furthermore, miRNA array analysis identified five candidate miRNAs (miR‑299a‑5p, miR‑206‑3p, miR‑325‑5p, miR‑10b‑5p, miR‑429‑3p) that are highly likely to be associated with MS pathogenesis, which could be helpful in the diagnosis and treatment of MS disease. This research offers vital insights that could be utilized in creating biomarkers and advancing treatments for MS.

Integrative Transcriptomic and Small RNA Analysis Uncovers Key Genes for Cold Resistance in Rice.

Cold stress is the main environmental factor that affects the growth and development of rice, leading to a decrease in its yield and quality. However, the molecular mechanism of rice's low-temperature resistance remains incompletely understood. In this study, we conducted a joint analysis of miRNA and mRNA expression profiles in the cold-resistant material Yongning red rice and the cold-sensitive material B3 using high-throughput sequencing. 194 differentially expressed miRNAs (DEMIs) and 14,671 differentially expressed mRNAs (DEMs) were identified. Among them, 19 DEMIs, including miR1437, miR1156, miR166, miR1861, and miR396_2 family members, showed opposite expression during the early or late stages of low-temperature treatment in two varieties, while 13 DEMIs were specifically expressed in Yongning red rice, indicating that these miRNAs are involved in rice's resistance to low temperature. In the transcriptome analysis, 218 DEMs exhibited opposite expressions during the early or late stages of low-temperature treatment in two varieties. GO enrichment analysis indicated that these DEMs were enriched in biological processes such as a defense response to fungi, a defense response to bacteria, a plant-type cell wall modification, single-organism cellular processes, a response to chitin, and the regulation of a plant-type hypersensitive response, as well as in cellular components such as the apoplast, nucleus, vacuole, plasma membrane, and plasmodesma. Twenty-one genes were further selected as potential candidates for low-temperature resistance. The joint analysis of miRNA and mRNA expression profiles showed that 38 miRNAs corresponding to 39 target genes were candidate miRNA-mRNA pairs for low-temperature resistance. This study provides valuable resources for determining the changes in miRNA and mRNA expression profiles induced by low temperatures and enables the provision of valuable information for further investigating the molecular mechanisms of plant resistance to low temperatures and for the genetic improvement of cold-resistant varieties.

Angiogenesis-promoting effect of SKP-SC-EVs-derived miRNA-30a-5p in peripheral nerve regeneration by targeting LIF and ANGPT2.

Ischemia and hypoxia caused by vascular injury intensify nerve damage. Skin precursor-derived Schwann cells have demonstrated an accelerated in vivo pre-vascularization of tissue-engineered nerves. Furthermore, extracellular vesicles from skin precursor-derived Schwann cells (SKP-SC-EVs) show the potential in aiding peripheral nerve regeneration. Nonetheless, the capacity of SKP-SC-EVs to facilitate nerve repair via angiogenesis remains uncertain. This study observed that SKP-SC-EVs significantly enhanced angiogenesis, evidenced by increased transparency of the tissue-engineered nerve graft and ultrasonic blood flow imaging. In vitro experiments confirmed that SKP-SC-EVs promote the proliferation, migration, and tube formation of human umbilical vein endothelial cells, a standard model for assessing angiogenic potential. Additionally, a comprehensive microRNA (miRNA) expression profile of SKP-SC-EVs was performed, leading to the identification of potential candidates through functional experiments. Among these, miR-30a-5p emerged as a significant candidate, demonstrating remarkable pro-angiogenic effects both in vivo and in vitro, akin to the effects of SKP-SC-EVs. Furthermore, luciferase reporter assay and functional experiments revealed that miR-30a-5p in SKP-SC-EVs promotes angiogenesis by targeting ANGPT2 and LIF without sufficient VEGFa. Thus, the enrichment of miR-30a-5p in SKP-SC-EVs indicates its pivotal role as a regulator of angiogenesis, presenting a promising avenue for cell-free treatment of peripheral nerve injury.

Deer antler reserve mesenchyme cells modified with miR-145 promote chondrogenesis in cartilage regeneration.

Deer antler-derived reserve mesenchyme cells (RMCs) are a promising source of cells for cartilage regeneration therapy due to their chondrogenic differentiation potential. However, the regulatory mechanism has not yet been elucidated. In this study, we analyzed the role of microRNAs (miRNAs) in regulating the differentiation of RMCs and in the post-transcriptional regulation of chondrogenesis and hypertrophic differentiation at the molecular and histological levels. The results showed that RMCs showed typical MSC differentiation potentials. During chondrogenic differentiation, we obtained the expression profile of miRNAs, among which miR- 145 was the most prominent candidate as a key microRNA involved in the balance of chondral and endochondral differentiation. Knockdown of miR-145 promoted chondrogenesis and inhibited hypertrophy differentiation in RMCs. Mechanically, by prediction through online databases combined with dual-luciferase reporter assay, SOX9 was suggested as a target of miR-145. Further validation experiments confirmed that knockdown of miR-145 contributed to the balance between endochondral versus chondral differentiation of RMCs by targeting SOX9. Additionally, RMCs transfected with the miR-145-knockdown-mediated lentiviral vector successfully promoted cartilage regeneration in vivo. In summary, our study suggested that the reciprocal negative feedback between SOX9 and miR-145 was essential for balancing between endochondral versus chondral differentiation of RMCs. Our study suggested that modification of RMCs using miRNAs transduction might be an effective treatment for cartilage defects.