Role Of microRNAs In Regulation Research Articles

Polyphyllin VII enhances the sensitivity of endometrial carcinoma cells to medroxyprogesterone acetate through upregulating miR‑33a‑5p expression.

Endometrial carcinoma (EC) often exhibits resistance to hormone therapies, such as medroxyprogesterone acetate (MPA), highlighting the need for novel strategies to enhance therapeutic efficacy. The present study aimed to investigate the effects of polyphyllin VII (PPVII) on the efficacy of MPA in EC, focusing on the regulatory role of microRNA (miR)-33a-5p. Briefly, an MPA-resistant Ishikawa cell line (Ishikawa/MPA-R), maintained with 10 µM MPA, was established and transfected with negative control (NC) and miR-33a-5p inhibitors. Following treatment with PPVII and MPA, the proliferation capacity and apoptosis levels of the Ishikawa and Ishikawa/MPA-R cells were evaluated using reverse transcription-quantitative polymerase chain reaction, MTT assay, clonogenic assay, flow cytometry, western blotting and dual-luciferase assay. Next, the expression levels of miR-33a-5p and F-box and leucine rich repeat protein 16 (FBXL16) were measured, and the regulatory relationship between miR-33a-5p and FBXL16 was analyzed. Significant reductions in cell viability were observed in all groups following treatment with increased concentrations of MPA and PPVII, with the greatest effect observed in the combined MPA + PPVII group (P<0.01). The apoptosis levels of the Ishikawa/MPA-R cells were significantly increased in all drug treatment groups, particularly in the MPA + PPVII group (P<0.05). PPVII treatment significantly increased the expression level of miR-33a-5p in Ishikawa/MPA-R cells (P<0.01). In the PPVII + miR-33a-5p inhibitor group, the Ishikawa/MPA-R cells exhibited an upregulation in the viability (P<0.01), colony formation ability (P<0.01), proportion in the G1 phase (P<0.05) and the protein expression levels of cyclin D1 (P<0.01) and cyclin-dependent kinase 4 (P<0.01), and a reduction in the miR-33a-5p expression (P<0.01), apoptosis levels (P<0.05), proportion in the S (P<0.05) and G2 phases and the levels of Bcl-2-associated X protein (P<0.001). The FBXL16 protein expression in Ishikawa/MPA-R cells was significantly higher compared with Ishikawa cells, and the mRNA and protein expression levels of FBXL16 were markedly elevated in the PPVII + miR-33a-5p inhibitor group compared with the PPVII + NC group (P<0.01). These findings suggested that PPVII upregulated the expression of miR-33a-5p, enhanced the sensitivity of EC cells to MPA and potentially exerted anticancer effects in EC through the synergistic action of the miR-33a-5p/FBXL16 axis in combination with MPA.

UNRAVELING THE GENETIC AND EPIGENETIC LANDSCAPE OF RHEUMATOID ARTHRITIS: A COMPREHENSIVE REVIEW OF PATHOGENESIS, DIAGNOSIS, AND THERAPEUTIC IMPLICATIONS

This exhaustive review delves into the genetic and epigenetic foundations of Rheumatoid Arthritis (RA), a multifaceted autoimmune disorder characterized by persistent joint inflammation. We discuss the findings of genome-wide association studies (GWAS) that have uncovered numerous genetic loci associated with RA, emphasizing the substantial impact of HLA variants on disease susceptibility and severity. The review also explores epigenetic mechanisms such as DNA methylation, histone modifications, and the regulatory role of microRNAs, all of which influence gene expression and immune response in RA. The involvement of inflammasomes in mediating inflammatory responses emphasizes potential therapeutic targets. Furthermore, the application of artificial intelligence for analyzing intricate genetic data presents promising opportunities for advancing diagnosis and treatment strategies. This article underscores the critical need for integrating multi-omics data. It emphasizes the significance of collaborative research in the field of RA, highlighting the importance of your work in this area.

Identification of N7-methylguanosine-related miRNAs as potential biomarkers for prognosis and drug response in breast cancer

ObjectivesThe impact of N7-methylguanosine (m7G) on tumor progression and the regulatory role of microRNAs (miRNAs) in immune function significantly influence breast cancer (BC) prognosis. Investigating the interplay between m7G modification and miRNAs provides novel insights for assessing prognostics and drug responses in BC. Materials and methodsRNA sequences (miRNA and mRNA profiles) and clinical data for BC were acquired from the Cancer Genome Atlas (TCGA) database. A miRNA signature associated with 15 m7G in this cohort was identified using Cox regression and LASSO. The risk score model was evaluated using Kaplan-Meier and time-dependent ROC analysis, categorizing patients into high-risk and low-risk groups. Functional enrichment analyses were conducted to explore potential pathways. The immune system, including scores, cell infiltration, function, and drug sensitivity, was examined and compared between high-risk and low-risk groups. A nomogram that combines risk scores and clinical factors was developed and validated. Single-sample gene set enrichment analysis (ssGSEA) was employed to explore m7G-related miRNA signatures and immune cell relationships in the tumor microenvironment. Additionally, drug susceptibility was compared between risk groups. ResultsFifteen m7G-related miRNAs were independently correlated with overall survival (OS) in BC patients. Time-dependent ROC analysis yielded area under the curve (AUC) values of 0.742, 0.726, and 0.712 for predicting 3-, 5-, and 10-year survival rates, respectively. The Kaplan-Meier analysis revealed a significant disparity in OS between the high-risk and low-risk groups (p = 1.3e-6). Multiple regression identified the risk score as a significant independent prognostic factor. An excellent calibration nomogram with a C-index of 0.785 (95 % CI: 0.728–0.843) was constructed. In immune analysis, low-risk patients exhibited heightened immune function and increased responsiveness to immunotherapy and chemotherapy compared to high-risk patients. ConclusionThis study systematically analyzed m7G-related miRNAs and revealed their regulatory mechanisms concerning the tumor microenvironment (TME), pathology, and the prognosis of BC patient. Based on these miRNAs, a prognostic model and nomogram were developed for BC patients, facilitating prognostic assessments. These findings can also assist in predicting treatment responses and guiding medication selection.

Regulatory Pathways in Growth Plate Chondrocytes that Are Impacted by Matrix Vesicle microRNA Identified by Targeted RISC Pulldown and Sequencing of the Resulting Transcriptome.

During endochondral bone formation, growth plate chondrocytes are differentially regulated by various factors and hormones. As the cellular phenotype changes, the composition of the extracellular matrix is altered, including the production and composition of matrix vesicles (MV) and their cargo of microRNA. The regulatory functions of these MV microRNA in the growth plate are still largely unknown. To address this question, we undertook a targeted bioinformatics approach. A subset of five MV microRNA was selected for analysis based on their specific enrichment in these extracellular vesicles compared to the parent cells (miR-1-3p, miR-22-3p, miR-30c-5p, miR-122-5p, and miR-133a-3p). Synthetic biotinylated versions of the microRNA were produced using locked nucleic acid (LNA) and were transfected into rat growth plate chondrocytes. The resulting LNA to mRNA complexes were pulled down and sequenced, and the transcriptomic data were used to run pathway analysis pipelines. Bone and musculoskeletal pathways were discovered to be regulated by the specific microRNA, notably those associated with transforming growth factor beta (TGFβ) and Wnt pathways, cell differentiation and proliferation, and regulation of vesicles and calcium transport. These results can help with understanding the maturation of the growth plate and the regulatory role of microRNA in MV.

Advancements in the Regulatory Role of microRNAs in Childhood Acute Lymphoblastic Leukemia: Mechanisms and Clinical Implications.

microRNAs (miRNAs), tiny, non-coding RNA molecules, fine-tune the expression of target genes through interacting with mRNAs. These miRNAs are involved in a wide range of biological processes, encompassing cell division, death, blood cell production, and tumor development. When these miRNAs become dysfunctional, they can promote the invasion and spread of cancer cells in various human malignancies, including leukemia. Acute lymphoblastic leukemia (ALL), the preeminent malignancy affecting children, is a blood cancer marked by the uncontrollable growth of immature lymphoid cells that displace healthy blood precursors in the bone marrow. Despite a decline in ALL mortality rates over the past two decades, a significant proportion of deaths still results from a lack of effective diagnostic and prognostic markers that can guide treatment decisions and overcome drug resistance. The analysis of miRNA expression patterns in ALL could lead to more precise disease classification, earlier diagnosis, and better prognostic outcomes in the near future. The connection between miRNA dysfunction and the biology of ALL suggests that these molecules could represent promising therapeutic targets. Therefore, this review delves into the regulatory mechanisms of miRNAs in pediatric ALL, exploring how miRNA-based diagnostic, prognostic, and therapeutic strategies offer unique advantages and hold promise for clinical applications.

Evidence for Functional Roles of MicroRNAs in Lineage Specification During Mouse and Human Preimplantation Development.

Proper formation of the blastocyst, including the specification of the first embryonic cellular lineages, is required to ensure healthy embryo development and can significantly impact the success of assisted reproductive technologies (ARTs). However, the regulatory role of microRNAs in early development, particularly in the context of preimplantation lineage specification, remains largely unknown. Taking a cross-species approach, this review aims to summarize the expression dynamics and functional significance of microRNAs in the differentiation and maintenance of lineage identity in both the mouse and the human. Findings are consolidated from studies conducted using in vitro embryonic stem cell models representing the epiblast, trophectoderm, and primitive endoderm lineages (modeled by naïve embryonic stem cells, trophoblast stem cells, and extraembryonic endoderm stem cells, respectively) to provide insight on what may be occurring in the embryo. Additionally, studies directly conducted in both mouse and human embryos are discussed, emphasizing similarities to the stem cell models and the gaps in our understanding, which will hopefully lead to further investigation of these areas. By unraveling the intricate mechanisms by which microRNAs regulate the specification and maintenance of cellular lineages in the blastocyst, we can leverage this knowledge to further optimize stem cell-based models such as the blastoids, enhance embryo competence, and develop methods of non-invasive embryo selection, which can potentially increase the success rates of assisted reproductive technologies and improve the experiences of those receiving fertility treatments.

The Regulatory Role of MicroRNAs in Obesity and Obesity-Derived Ailments.

Obesity is a condition that is characterized by the presence of excessive adipose tissue in the body. Obesity has become one of the main health concerns worldwide since it can lead to other chronic ailments, such as type 2 diabetes or fatty liver disease, and it could be an aggravating factor in infections. MicroRNAs (miRNAs) are small, non-coding RNA molecules that regulate gene expression and can play an important role in controlling crucial biological processes involved in the onset of obesity, such as lipogenesis, adipogenesis, lipid metabolism, or the regulation of cytokines and chemokines. Moreover, chemical compounds present in food or food packaging can alter miRNA expression and regulate the aforementioned biological mechanisms related to diabetes onset and progression. Furthermore, therapies, such as bariatric surgery and aerobic exercise training, can also influence the expression profile of miRNAs in obesity. Therefore, the present review provides insight into the current research on the role of miRNAs in obesity and obesity-derived ailments, intending to develop novel therapies to effectively manage these disorders.

Regulatory Roles of MicroRNAs in the Pathogenesis of Metabolic Syndrome.

Metabolic syndrome refers to a group of several disease conditions together with high glucose triglyceride levels, high blood pressure, lower high-density lipoprotein level, and large waist circumference. About 400 million people worldwide, one-third of the Euro-American population and 27% Chinese population over age 50 have it. microRNAs, an abundant novel class of endogenous small, non-coding RNAs in eukaryotic cells, act as negative controllers of gene expression by promoting either degradation/translational repression of target messenger RNA. More than 2000 microRNAs in the human genome have been identified and they are implicated in various biological & pathophysiological processes, including glucose homeostasis, inflammatory response, and angiogenesis. Destruction of microRNAs has a crucial role in the pathogenesis of obesity, cardiovascular disease, and diabetes. Recently the discovery of circulating microRNAs in human serum may help to promote metabolic crosstalk between organs and serves as a novel approach for the identification of various diseases, like Type 2 diabetes & atherosclerosis. In this review, we will discuss the most recent and up-to-date research on the pathophysiology and histopathology of metabolic syndrome besides their historical background and epidemiological highlight. As well as search the methodologies employed in this field of research and the potential role of microRNAs as novel biomarkers and therapeutic targets for metabolic syndrome in the human body. Furthermore, the significance of microRNAs in promising strategies, like stem cell therapy, which holds enormous promise for regenerative medicine in the treatment of metabolic disorders will also be discussed.

Role of MicroRNAs in Regulation of Cellular Response to Hypoxia.

Hypoxia causes changes in transcription of the genes that contribute to adaptation of the cells to low levels of oxygen. The main mechanism regulating cellular response to hypoxia is activation of hypoxia-inducible transcription factors (HIF), which include several isoforms and control expression of more than a thousand genes. HIF activity is regulated at various levels, including by small non-coding RNA molecules called microRNAs (miRNAs). miRNAs regulate cellular response to hypoxia by influencing activation of HIF, its degradation, and translation of HIF-dependent proteins. At the same time, HIFs also affect miRNAs biogenesis. Data on the relationship of a particular HIF isoform with miRNAs are contradictory, since studies have been performed using different cell lines, various types of experimental animals and clinical material, as well as at different oxygen concentrations and durations of hypoxic exposure. In addition, HIF expression may be affected by the initial resistance of organisms to lack of oxygen, which has not been taken into account in the studies. This review analyzes the data on the effect of hypoxia on biogenesis and functioning of miRNAs, as well as on the effect of miRNAs on mRNAs of the genes involved in adaptation to oxygen deficiency. Understanding the mechanisms of relationship between HIF, hypoxia, and miRNA is necessary to develop new approaches to personalized therapy for diseases accompanied by oxygen deficiency.

Major considerations of nutrological aspects, gut microbiota, and regulation (down or up-regulation) of microRNAs/exosomes in inflammatory bowel diseases: a systematic review

Introduction: Inflammatory bowel diseases (IBD) are multifactorial, chronic, continuous, relapsing, and immune-mediated diseases of the gastrointestinal tract. The pathogenesis of IBD is linked to genetically susceptible individuals, dysregulated gut microbiota (dysbiosis), chronic inflammation, and poor dietary patterns. Diet and microRNAs/exosomes play an important role in modulating the intestinal microbiota, and can be applied as a therapeutic tool to improve the course of IBD. Objective: It was to carry out a systematic review of the main considerations of nutrological aspects, intestinal microbiota, and the regulation (Down or Up-regulation) and modulation of microRNAs/exosomes in inflammatory bowel diseases. Methods: The present study followed the international model of systematic review and meta-analysis (PRISMA). Clinical studies were included, involving randomized controlled, prospective, and retrospective studies, as well as pre-clinical studies, published in previous years as gold standard articles until 2023. Results and Conclusion: A total of 154 articles were found. A total of 78 articles were fully evaluated and 55 were included in this systematic review. Considering the Cochrane tool for risk of bias, 22 studies with a high risk of bias and 24 studies that did not meet the GRADE were removed. Most studies showed homogeneity in their results, with X2 =93.5% &gt;50%. The present study analyzed the main interactions between dietary therapy, intestinal microbiota, microRNAs, exosomes, and inflammatory bowel disease, elucidating the main clinical outcomes of the disease after nutrological treatment. As a corollary, important randomized controlled clinical studies were found in the last ten years that showed the important role of diet modulation in the control and even in the remission of inflammatory bowel disease, revealing important reductions in persistent intestinal symptoms, in the balance of the intestinal microbiota, in the regulatory role of microRNAs, reducing inflammation markers and improving quality of life. Recognition of the need for additional data from clinical trials, the inherent uncertainty of efficacy for all inflammatory bowel disease therapies, and the potential for benefit with dietary interventions will help guide progress toward a better understanding of the usefulness of dietary therapy for individuals with inflammatory bowel disease.

Inflammatory microRNAs in cardiovascular pathology: another brick in the wall.

The regulatory role of microRNAs (miRNAs) is mainly mediated by their effect on protein expression and is recognized in a multitude of pathophysiological processes. In recent decades, accumulating evidence has interest in these factors as modulatory elements of cardiovascular pathophysiology. Furthermore, additional biological processes have been identified as new components of cardiovascular disease etiology. In particular, inflammation is now considered an important cardiovascular risk factor. Thus, in the present review, we will focus on the role of a subset of miRNAs called inflamma-miRs that may regulate inflammatory status in the development of cardiovascular pathology. According to published data, the most representative candidates that play functional roles in thromboinflammation are miR-21, miR-33, miR-34a, miR-146a, miR-155, and miR-223. We will describe the functions of these miRNAs in several cardiovascular pathologies in depth, with specific emphasis on the molecular mechanisms related to atherogenesis. We will also discuss the latest findings on the role of miRNAs as regulators of neutrophil extracellular traps and their impact on cardiovascular diseases. Overall, the data suggest that the use of miRNAs as therapeutic tools or biomarkers may improve the diagnosis or prognosis of adverse cardiovascular events in inflammatory diseases. Thus, targeting or increasing the levels of adequate inflamma-miRs at different stages of disease could help mitigate or avoid the development of cardiovascular morbidities.

The regulatory role of microRNAs in common eye diseases: A brief review.

MicroRNAs (miRNAs) are highly conserved, small non-coding RNA molecules (∼21 nucleotides) that regulate numerous biological processes, including developmental timing, hematopoiesis, organogenesis, apoptosis, cell differentiation, and proliferation either by mRNA degradation or translation repression. Since eye physiology requires a perfect orchestration of complex regulatory networks, an altered expression of key regulatory molecules such as miRNAs potentially leads to numerous eye disorders. In recent years, comprehensive progress has been made in demonstrating the precise roles of miRNAs, emphasizing their potential use in diagnostic and therapeutic purposes of chronic human diseases. Thus, this review explicitly illustrates the regulatory roles of miRNAs in four common eye disorders, such as cataract, glaucoma, macular degeneration, and uveitis, and their application in disease management.

Role of microRNA in regulation of synaptic plasticity during post-traumatic stress disorder

Post-traumatic stress disorder (PTSD) is an incapacitating mental condition that develops after exposure to a disconcerting event. Failure to forget traumatic memories can lead to the development of fear memory associated with PTSD. Recent research exploring the molecular mechanism of memory dysfunction during PTSD was based on histone modification and DNA methylation, ignoring the role of non-coding sequences such as micro RNA (miRNA). Therefore, we review how miRNA regulates synaptic plasticity genes during PTSD-associated fear memory consolidation and extinction. We hypothesize that the miRNA will increase the expression of different synaptic plasticity genes in different brain subregions during PTSD. Since available treatment options are not sufficient, identifying new therapies is essential. More studies can define a therapeutic window for such interventions, helping to spread alternative supportive therapies for the treatment of PTSD. Moreover, our discussion might shed new light on the significance of miRNA (miRNA- 142) in regulating synaptic plasticity genes.

Baseline Circulating miR-125b Levels Predict a High FIB-4 Index Score in Chronic Hepatitis B Patients after Nucleos(t)ide Analog Treatment.

The regulatory role of microRNAs (miRNAs) in HBV-associated HCC pathogenesis has been reported previously. This study aimed to investigate the association between serum miR-125b and liver fibrosis progression in chronic hepatitis B (CHB) patients after nucleos(t)ide analog (NA) treatment. Baseline serum miR-125b levels and other relevant laboratory data were measured for 124 patients who underwent 12-month NA therapy. Post-12-month NA therapy, serum miR-125, platelet, AST, and ALT levels were measured again for post-treatment FIB-4 index calculation. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors for a higher post-treatment FIB-4 index. Results showed that baseline miR-125b levels were inversely correlated with the post-treatment FIB-4 index (ρ = -0.2130, p = 0.0082). In logistic regression analyses, age (OR = 1.17, p &lt; 0.0001), baseline platelet level (OR = 0.98, p = 0.0032), and ALT level (OR = 1.00, p = 0.0241) were independent predictors of FIB-index &gt; 2.9 post-12-month treatment. The baseline miR-125b level was not significantly associated with a higher post-treatment FIB-4 index (p = 0.8992). In 59 patients receiving entecavir (ETV) monotherapy, the alternation of serum miR-125b in 12 months and age were substantially associated with a higher post-treatment FIB-4 index (&gt; 2.9), suggesting that miR-125b is a reliable biomarker for detecting early liver fibrosis under specific anti-HBV NA treatments (e.g., ETV).

MicroRNA-486-5p suppresses inflammatory response by targeting FOXO1 in MSU-treated macrophages

Gouty arthritis (GA) is mainly caused by the precipitation of monosodium urate (MSU) crystals in the joint. Recently, different regulatory roles of microRNAs (miRNAs) in arthritis have been widely verified. Nevertheless, the specific function of microRNA-486-5p (miR-486-5p) in GA is still unclear. GA cell models in vitro were established by the treatment of 250 μg/mL MSU crystals into THP-1 cells or J774A.1 cells. Then, the accumulation of tumor necrosis factor (TNF)-α, interleukin (IL)-8, and IL-β was estimated by ELISA. The mRNA levels of TNF-α, IL-8, and IL-β were measured through RT-qPCR. The protein level of forkhead box protein O1 (FOXO1) was tested via western blot. Furthermore, the interplay of miR-486-5p and FOXO1 was evaluated via the luciferase reporter assay. In this study, MSU treatment successfully stimulated the inflammatory response in macrophage cells. MiR-486-5p downregulation was observed in THP-1 and J774A.1 cells treated with MSU, and its upregulation markedly decreased the concentration and mRNA levels of TNF-α, IL-8, and IL-β. Furthermore, FOXO1 was demonstrated to be negatively modulated by miR-486-5p. The rescue assay indicated that overexpressing FOXO1 reversed the effects of overexpressing miR-486-5p on inflammatory cytokines. Overall, this study proves that miR-486-5p inhibits GA inflammatory response via modulating FOXO1.

Corrigendum: Sea urchins in acute high temperature and low oxygen environments: The regulatory role of microRNAs in response to environmental stress

Corrigendum: Sea urchins in acute high temperature and low oxygen environments: The regulatory role of microRNAs in response to environmental stress

Role of microRNAs in regulation of insulin secretion and insulin signaling involved in type 2 diabetes mellitus

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder due to insulin resistance that can be caused by both genetic and environmental factors. In 2018, the American Diabetes Association (ADA) estimated more than 500 million T2DM cases globally. In recent years, studies conducted on humans and animals have suggested that non-coding RNAs, namely, microRNAs (miRNAs), post-transcriptionally regulate gene expression that can bring changes in normal physiology, resulting in the development of metabolic diseases. miRNAs also regulate different cellular processes including insulin synthesis and its secretion from pancreatic β-islet cells, its development and function, insulin signaling and glucose homeostasis. Dysregulation of miRNA can affect the functioning of different tissues during the progression of T2DM. This review focuses on various miRNAs that influence the development of β-cells and insulin secretion, various protein cascades that play an important role in insulin signaling and glucose uptake, and their role in insulin resistance. Similarly, the long noncoding RNAs also known as lncRNAs and their β-cell characteristics involved in T2DM have been discussed. Finally, the significance of miRNAs and their mRNA targets as effective biomarkers and therapeutics in studying the early onset and progression of T2DM have been highlighted.

Activating transcription factor 4-dependent hsa-miR-663a transcription mediates mTORC1/p70S6K1 signaling underleucine deprivation.

The mechanistic target of rapamycin complex 1 (mTORC1) is involved in nutrient-induced signaling and is a master regulator of cell growth and metabolism. Amino acid-deficient conditions affect mTORC1 activity; however, its upstream regulators warrant further investigation. MicroRNAs are key regulators of nutrient-related responses; therefore, the present study aimed to assess the leucine starvation-induced microRNA profile and its impact on mTORC1 activity. Transcriptome analysis of human hepatocellular carcinoma cells (HepG2) under leucine deprivation revealed that hsa-miR-663a and hsa-miR-1469 were altered in a transcription factor 4-dependent manner. Overexpression of these microRNAs induced phosphorylation of the ribosomal protein S6 kinase beta-1, a mTORC1 downstream target. Furthermore, hsa-miR-663a downregulated proline-rich Akt1 substrate of 40 kDa (PRAS40), one of the mTORC1 components. In summary, this study provides new insights into the regulatory role of microRNAs in amino acid metabolism and demonstrates alterations in microRNA profile under leucine deprivation in human hepatocytes.

The Etiology and Molecular Mechanism Underlying Smooth Muscle Phenotype Switching in Intimal Hyperplasia of Vein Graft and the Regulatory Role of microRNAs.

Mounting evidence suggests that the phenotypic transformation of venous smooth muscle cells (SMCs) from differentiated (contractile) to dedifferentiated (proliferative and migratory) phenotypes causes excessive proliferation and further migration to the intima leading to intimal hyperplasia, which represents one of the key pathophysiological mechanisms of vein graft restenosis. In recent years, numerous miRNAs have been identified as specific phenotypic regulators of vascular SMCs (VSMCs), which play a vital role in intimal hyperplasia in vein grafts. The review sought to provide a comprehensive overview of the etiology of intimal hyperplasia, factors affecting the phenotypic transformation of VSMCs in vein graft, and molecular mechanisms of miRNAs involved in SMCs phenotypic modulation in intimal hyperplasia of vein graft reported in recent years.

Integrated SRNA-Seq and RNA-Seq Analysis Reveals the Regulatory Roles of miRNAs in the Low-Temperature Responses of Canarium album

Chinese olive (Canarium album), a characteristic fruit tree in tropical and subtropical areas, suffers greatly from low-temperature stress (LTS). The regulatory roles of microRNA (miRNA) in plant LTS responses have been confirmed in many plant species but not in C. album. In this study, a cold-tolerant cultivar ‘Rui’an 3′ (RA) and a susceptible cultivar ‘Qinglan 1’ (QL) treated at 25 °C (control, CK) and −3 °C (cold temperature treatment, CT) were subjected to small RNA (sRNA) and transcriptome sequencing for the exploration of the cold responses of C. album. Comparative sRNA sequencing analysis identified much fewer LTS-responsive, differentially expressed miRNAs (DEMs) in RA (4 DEMs) than in QL (23 DEMs). Cal-miR482-22 was found to be specifically induced by LTS in RA. Cal-miR397-3 was upregulated, while cal-miR398_2-3 and cal-undef-190 were downregulated after LTS only in QL. However, when compared with QL, a higher basic expression of cal-miR397-3, and lower expression of cal-miR398_2-3 and cal-undef-190 were found in RA, suggesting that they may contribute to the cold tolerance of RA. Comparative transcriptome analysis showed that the number of LTS-responsive differentially expressed genes (DEGs) identified in QL was larger than that in RA, and some DEGs were also predicted as the target genes of the identified DEMs, forming multiple differentially expressed miRNA–target gene pairs, such as cal-miR397-3_laccase 2, 4, 17, cal-miR482-22_suppressor of npr1-1, etc. Quantitative real time PCR results showed that the expression changes of DEGs and DEMs in different samples were generally consistent with the sequencing results. Our study indicated that the basic expression levels of some miRNAs (especially the cal-miR397-3, cal-miR398_2-3, and cal-miR482-22), and their target genes contribute greatly to the cold-tolerance characteristics of C. album. Our study is helpful for understanding the roles of miRNAs in the cold resistance and responses of C. album.