Modulation Of miRNA Expression Research Articles

Effects of Multi-species Synbiotic Supplementation on Circulating miR-27a, miR-33a Levels, and Lipid Parameters in Adult Men with Dyslipidemia; A Randomized, Double-Blind, Placebo-Controlled Clinical Trial.

MicroRNAs (miRNAs) have emerged as important regulators of lipid metabolism. Recent studies have suggested synbiotics may modulate miRNA expression and lipid metabolism. This study aimed to investigate the effects of synbiotic supplementation on circulating miR-27a, miR-33a, and lipid parameters in patients with dyslipidemia. Fifty-six eligible participants were randomly allocated to receive either synbiotic or placebo sachets twice a day for 12 weeks. Each synbiotic sachet contained 3×1010 CFU six species of probiotic microorganisms and 5 grams of inulin and fructooligosaccharide (FOS) as prebiotics. Serum miR-27a and miR-33a expression levels, serum lipids, and apolipoproteins, the fecal concentration of short-chain fatty acids (SCFAs), and Firmicutes and Bacteroidetes phyla were assessed before and after the study. Real-time PCR was used to determine the relative expression levels of miRNAs. The results showed synbiotic supplementation significantly downregulated the expression levels of miR-27a and miR-33a compared to the placebo group (p = 0.008 and p = 0.001, respectively). Furthermore, the intervention group exhibited significant improvements in serum high-density lipoprotein (HDL-C), small dense low-density lipoprotein (sdLDL-C), apoA-I, and apoB-100 (p = 0.008, p = 0.006, p = 0.003, p = 0.001, respectively). The results showed a significant negative correlation between miR-33a expression levels with HDL-C, butyrate, propionate, and a significant positive correlation with total cholesterol (TC), low-density lipoprotein (LDL-C), and sdLDL-C in the intervention group. Fecal bacteria and SCFAs were significantly increased in the intervention group. This study provides evidence that synbiotic supplementation can modulate miR-27a and miR-33a expression and improve lipid metabolism in patients with dyslipidemia.

Effects of Slow Freezing and Vitrification of Human Semen on Post-Thaw Semen Quality and miRNA Expression.

Semen cryopreservation has played an important role in medically assisted reproduction for decades. In addition to preserving male fertility, it is sometimes used for overcoming logistical issues. Despite its proven clinical usability and safety, there is a lack of knowledge of how it affects spermatozoa at the molecular level, especially in terms of non-coding RNAs. Therefore, we conducted this study, where we compared slow freezing and vitrification of good- and poor-quality human semen samples by analyzing conventional sperm quality parameters, performing functional tests and analyzing the expression of miRNAs. The results revealed that cryopreservation of normozoospermic samples does not alter the maturity of spermatozoa (protamine staining, hyaluronan binding), although cryopreservation can increase sperm DNA fragmentation and lower motility. On a molecular level, we revealed that in both types of cryopreservation, miRNAs from spermatozoa are significantly overexpressed compared to those in the native semen of normozoospermic patients, but in oligozoospermic samples, this effect is observed only after vitrification. Moreover, we show that expression of selected miRNAs is mostly overexpressed in native oligozoospermic samples compared to normozoospermic samples. Conversely, when vitrified normozoospermic and oligozoospermic samples were compared, we determined that only miR-99b-5p was significantly overexpressed in oligozoospermic sperm samples, and when comparing slow freezing, only miR-15b-5p and miR-34b-3p were significantly under-expressed in oligozoospermic sperm samples. Therefore, our results imply that cryopreservation of normozoospermic sperm samples can modulate miRNA expression profiles in spermatozoa to become comparable to those in oligozoospermic samples.

Neuron enriched extracellular vesicles’ MicroRNA expression profiles as a marker of early life alcohol consumption

Alcohol consumption may impact and shape brain development through perturbed biological pathways and impaired molecular functions. We investigated the relationship between alcohol consumption rates and neuron-enriched extracellular vesicles’ (EVs’) microRNA (miRNA) expression to better understand the impact of alcohol use on early life brain biology. Neuron-enriched EVs’ miRNA expression was measured from plasma samples collected from young people using a commercially available microarray platform while alcohol consumption was measured using the Alcohol Use Disorders Identification Test. Linear regression and network analyses were used to identify significantly differentially expressed miRNAs and to characterize the implicated biological pathways, respectively. Compared to alcohol naïve controls, young people reporting high alcohol consumption exhibited significantly higher expression of three neuron-enriched EVs’ miRNAs including miR-30a-5p, miR-194-5p, and miR-339-3p, although only miR-30a-5p and miR-194-5p survived multiple test correction. The miRNA-miRNA interaction network inferred by a network inference algorithm did not detect any differentially expressed miRNAs with a high cutoff on edge scores. However, when the cutoff of the algorithm was reduced, five miRNAs were identified as interacting with miR-194-5p and miR-30a-5p. These seven miRNAs were associated with 25 biological functions; miR-194-5p was the most highly connected node and was highly correlated with the other miRNAs in this cluster. Our observed association between neuron-enriched EVs’ miRNAs and alcohol consumption concurs with results from experimental animal models of alcohol use and suggests that high rates of alcohol consumption during the adolescent/young adult years may impact brain functioning and development by modulating miRNA expression.

Role of microRNA in colorectal carcinoma (CRC): a narrative review.

MicroRNAs (miRNAs) are short non-coding RNAs that play a critical role in regulating gene expression by binding to target messenger RNAs (mRNAs). They were first discovered around 8 years after the identification of the first miRNA in 1993, and since then, there has been a significant increase in miRNA-related research and discoveries. MiRNAs have been implicated in various biological processes, including cancer, particularly in colorectal cancer (CRC). In CRC, miRNAs act as either oncogenes or tumor suppressors, influencing essential cellular functions such as cell proliferation, apoptosis, angiogenesis, and metastasis. The dysregulation of miRNAs in CRC can arise from different factors, leading to abnormal expression levels of their target mRNAs and subsequently affecting protein production. Consequently, miRNAs may directly target oncogenes or tumor suppressor genes, thereby contributing to cancer initiation and progression. Notably, tumors often exhibit reduced expression of mature miRNAs. In CRC research, miRNAs offer potential as diagnostic biomarkers and therapeutic targets. Specific miRNA profiles could serve as non-invasive tools for early CRC detection and risk assessment. Additionally, miRNA-based therapies present a promising approach for targeted cancer treatment by modulating miRNA expression. However, challenges related to delivery systems and long-term safety must be addressed to fully harness their therapeutic potential.

The Parasite‐Derived Peptide, FhHDM‐1, Selectively Modulates miRNA Expression in β‐Cells to Prevent Apoptotic Pathways Induced by Proinflammatory Cytokines

The Parasite‐Derived Peptide, FhHDM‐1, Selectively Modulates miRNA Expression in <i>β</i>‐Cells to Prevent Apoptotic Pathways Induced by Proinflammatory Cytokines

The Parasite-Derived Peptide, FhHDM-1, Selectively Modulates miRNA Expression in β-Cells to Prevent Apoptotic Pathways Induced by Proinflammatory Cytokines.

We have previously identified a parasite-derived peptide, FhHDM-1, that prevented the progression of diabetes in nonobese diabetic (NOD) mice. Disease prevention was mediated by the activation of the PI3K/Akt pathway to promote β-cell survival and metabolism without inducing proliferation. To determine the molecular mechanisms driving the antidiabetogenic effects of FhHDM-1, miRNA:mRNA interactions and in silico predictions of the gene networks were characterised in β-cells, which were exposed to the proinflammatory cytokines that mediate β-cell destruction in Type 1 diabetes (T1D), in the presence and absence of FhHDM-1. The predicted gene targets of miRNAs differentially regulated by FhHDM-1 mapped to the biological pathways that regulate β-cell biology. Six miRNAs were identified as important nodes in the regulation of PI3K/Akt signaling. Additionally, IGF-2 was identified as a miRNA gene target that mediated the beneficial effects of FhHDM-1 on β-cells. The findings provide a putative mechanism by which FhHDM-1 positively impacts β-cells to permanently prevent diabetes. As β-cell death/dysfunction underlies diabetes development, FhHDM-1 opens new therapeutic avenues.

Regulating miRNAs Expression by Resveratrol: Novel Insights based on Molecular Mechanism and Strategies for Cancer Therapy.

Resveratrol, a polyphenolic phytoalexin found in a wide range of plants, including grapes, berries, and peanuts, is an extensively researched phytochemical with unique pharmacological capabilities and amazing potential to affect many targets in various cancers. Resveratrol's anti-cancer activities are due to its targeting of a variety of cellular and molecular mechanisms and crucial processes involved in cancer pathogenesis, such as the promotion of growth arrest, stimulation of apoptosis, suppression of cell proliferation, induction of autophagy, regulating oxidative stress and inflammation, and improving the influence of some of the other chemotherapeutic agents. MicroRNAs (miRNAs) are non-coding RNAs that modulate gene expression by degrading mRNA or inhibiting translation. MiRNAs serve critical roles in a wide range of biological activities, and disruption of miRNA expression is strongly linked to cancer progression. Recent research has shown that resveratrol has anti-proliferative and/or pro-apoptotic properties via modulating the miRNA network, which leads to the inhibition of tumor cell proliferation, the activation of apoptosis, or the increase of traditional cancer therapy effectiveness. As a result, employing resveratrol to target miRNAs will be a unique and potential anticancer approach. Here, we discuss the main advances in the modulation of miRNA expression by resveratrol, as well as the several miRNAs that may be influenced by resveratrol in different types of cancer and the significance of this natural drug as a promising strategy in cancer treatment.

Role of Dietary Phytochemicals in Targeting Human miRNAs for Cancer Prevention and Treatment.

MicroRNAs (miRNAs - ~22 nucleotides) are a type of non-coding RNAs that are involved in post-transcriptional gene silencing. They are known to regulate gene expression in diverse biological processes, such as apoptosis, development, and differentiation. Several studies have demonstrated that cancer initiation and progression are highly regulated by miRNA expression. The nutrients present in the diet may regulate the different stages of carcinogenesis. Interestingly, plant-based foods, like fruits and vegetables, have been shown to play a significant role in cancer prevention. Phytochemicals are bioactive compounds derived from plant sources, and they have been shown to have antiinflammatory, antioxidant, and anticancer properties. Recent findings suggest that dietary phytochemicals, such as genistein, resveratrol, and curcumin, exert significant anticancer effects by regulating various miRNAs. In this review, we focus on the role of dietary phytochemicals in cancer prevention and treatment through the modulation of miRNA expression.

New insights of miRNA molecular mechanisms in breast cancer brain metastasis and therapeutic targets

Brain metastases in breast cancer (BC) patients are often associated with a poor prognosis. Recent studies have uncovered the critical roles of miRNAs in the initiation and progression of BC brain metastasis, highlighting the disease's underlying molecular pathways. miRNA-181c, miRNA-10b, and miRNA-21, for example, are all overexpressed in BC patients. It has been shown that these three miRNAs help tumors grow and metastasize by targeting genes that control how cells work. On the other hand, miRNA-26b5p, miRNA-7, and miRNA-1013p are all downregulated in BC brain metastasis patients. They act as tumor suppressors by controlling the expression of genes related to cell adhesion, angiogenesis, and invasion. Therapeutic miRNA targeting has considerable promise in treating BC brain metastases. Several strategies have been proposed to modulate miRNA expression, including miRNA-Mimics, antagomirs, and small molecule inhibitors of miRNA biogenesis. This review discusses the aberrant expression of miRNAs and metastatic pathways that lead to the spread of BC cells to the brain. It also explores miRNA therapeutic target molecular mechanisms and BC brain metastasis challenges with advanced strategies. The targeting of certain miRNAs opens a new door for the development of novel therapeutic approaches for this devastating disease.

Cold water immersion in recovery following a single bout resistance exercise suppresses mechanisms of miRNA nuclear export and maturation.

Cold water immersion (CWI) following intense exercise is a common athletic recovery practice. However, CWI impacts muscle adaptations to exercise training, with attenuated muscle hypertrophy and increased angiogenesis. Tissue temperature modulates the abundance of specific miRNA species and thus CWI may affect muscle adaptations via modulating miRNA expression following a bout of exercise. The current study focused on the regulatory mechanisms involved in cleavage and nuclear export of mature miRNA, including DROSHA, EXPORTIN-5, and DICER. Muscle biopsies were obtained from the vastus lateralis of young males (n = 9) at rest and at 2, 4, and 48 h of recovery from an acute bout of resistance exercise, followed by either 10 min of active recovery (ACT) at ambient temperature or CWI at 10°C. The abundance of key miRNA species in the regulation of intracellular anabolic signaling (miR-1 and miR-133a) and angiogenesis (miR-15a and miR-126) were measured, along with several gene targets implicated in satellite cell dynamics (NCAM and PAX7) and angiogenesis (VEGF and SPRED-1). When compared to ACT, CWI suppressed mRNA expression of DROSHA (24 h p = 0.025 and 48 h p = 0.017), EXPORTIN-5 (24 h p = 0.008), and DICER (24 h p = 0.0034). Of the analyzed miRNA species, miR-133a (24 h p < 0.001 and 48 h p = 0.007) and miR-126 (24 h p < 0.001 and 48 h p < 0.001) remained elevated at 24 h post-exercise in the CWI trial only. Potential gene targets of these miRNA, however, did not differ between trials. CWI may therefore impact miRNA abundance in skeletal muscle, although the precise physiological relevance needs further investigation.

3D Culture and Interferon-γ Priming Modulates Characteristics of Mesenchymal Stromal/Stem Cells by Modifying the Expression of Both Intracellular and Exosomal microRNAs.

Mesenchymal stromal/stem cells (MSCs) have emerged as a therapeutic tool in regenerative medicine. Recent studies have shown that exosome (EXO)-derived microRNAs (miRNAs) play a crucial role in mediating MSC functions. Additionally, intracellular miRNAs have been found to regulate MSC therapeutic capacities. However, the molecular mechanisms underlying miRNA-mediated MSC effects are not fully understood. We used 3D culture and IFN-γ to prime/enhance the MSC therapeutic effects in terms of functional miRNAs. After priming, our analysis revealed stable variations in intracellular miRNA among the MSC biological replicates. Conversely, a significant variability of miRNA was observed among EXOs released from biological replicates of the priming treatment. For each priming, we observed distinct miRNA expression profiles between the MSCs and their EXOs. Moreover, in both types of priming, gene ontology (GO) analysis of deregulated miRNAs highlighted their involvement in tissue repair/regeneration pathways. In particular, the 3D culture enhanced angiogenic properties in both MSCs and EXOs, while IFN-γ treatment enriched miRNAs associated with immunomodulatory pathways. These findings suggest that 3D culture and IFN-γ treatment are promising strategies for enhancing the therapeutic potential of MSCs by modulating miRNA expression. Additionally, the identified miRNAs may contribute to understanding the molecular mechanisms underlying the miRNA-mediated therapeutic effects of MSCs.

The HOS15-HDA9 complex associates with HYL1 to modulate miRNA expression in response to ABA signaling.

The regulation of microRNA (miRNA) biogenesis is crucial for maintaining plant homeostasis under biotic and abiotic stress. The crosstalk between the RNA polymerase II (Pol-II) complex and the miRNA processing machinery has emerged as a central hub modulating transcription and co-transcriptional processing of primary miRNA transcripts (pri-miRNAs). However, it remains unclear how miRNA-specific transcriptional regulators recognize MIRNA loci. Here, we show that the Arabidopsis (Arabidopsis thaliana) HIGH EXPRESSION OF OSMOTICALLY RESPONSIVE GENE15 (HOS15)-HISTONE DEACETYLASE9 (HDA9) complex is a conditional suppressor of miRNA biogenesis, particularly in response to ABA. When treated with ABA, hos15/hda9 mutants show enhanced transcription of pri-miRNAs that is accompanied by increased processing, leading to over-accumulation of a set of mature miRNAs. Moreover, upon recognition of the nascent pri-miRNAs, the ABA-induced recruitment of the HOS15-HDA9 complex to MIRNA loci is guided by HYPONASTIC LEAVES 1 (HYL1). The HYL1-dependent recruitment of the HOS15-HDA9 complex to MIRNA loci suppresses expression of MIRNAs and processing of pri-miRNA. Most importantly, our findings indicate that nascent pri-miRNAs serve as scaffolds for recruiting transcriptional regulators, specifically to MIRNA loci. This indicates that RNA molecules can act as regulators of their own expression by causing a negative feedback loop that turns off their transcription, providing a self-buffering system.

NF-κB Signaling Modulates miR-452-5p and miR-335-5p Expression to Functionally Decrease Epithelial Ovarian Cancer Progression in Tumor-Initiating Cells.

Epithelial ovarian cancer (EOC) remains the fifth leading cause of cancer-related death in women worldwide, partly due to the survival of chemoresistant, stem-like tumor-initiating cells (TICs) that promote disease relapse. We previously described a role for the NF-κB pathway in promoting TIC chemoresistance and survival through NF-κB transcription factors (TFs) RelA and RelB, which regulate genes important for the inflammatory response and those associated with cancer, including microRNAs (miRNAs). We hypothesized that NF-κB signaling differentially regulates miRNA expression through RelA and RelB to support TIC persistence. Inducible shRNA was stably expressed in OV90 cells to knockdown RELA or RELB; miR-seq analyses identified differentially expressed miRNAs hsa-miR-452-5p and hsa-miR-335-5p in cells grown in TIC versus adherent conditions. We validated the miR-seq findings via qPCR in TIC or adherent conditions with RELA or RELB knocked-down. We confirmed decreased expression of hsa-miR-452-5p when either RELA or RELB were depleted and increased expression of hsa-miR-335-5p when RELA was depleted. Either inhibiting miR-452-5p or mimicking miR-335-5p functionally decreased the stem-like potential of the TICs. These results highlight a novel role of NF-κB TFs in modulating miRNA expression in EOC cells, thus opening a better understanding toward preventing recurrence of EOC.

Nucleolin Regulates Pulmonary Artery Smooth Muscle Cell Proliferation under Hypoxia by Modulating miRNA Expression

Hypoxia induces the abnormal proliferation of vascular smooth muscle cells (VSMCs), resulting in the pathogenesis of various vascular diseases. RNA-binding proteins (RBPs) are involved in a wide range of biological processes, including cell proliferation and responses to hypoxia. In this study, we observed that the RBP nucleolin (NCL) was downregulated by histone deacetylation in response to hypoxia. We evaluated its regulatory effects on miRNA expression under hypoxic conditions in pulmonary artery smooth muscle cells (PASMCs). miRNAs associated with NCL were assessed using RNA immunoprecipitation in PASMCs and small RNA sequencing. The expression of a set of miRNAs was increased by NCL but reduced by hypoxia-induced downregulation of NCL. The downregulation of miR-24-3p and miR-409-3p promoted PASMC proliferation under hypoxic conditions. These results clearly demonstrate the significance of NCL-miRNA interactions in the regulation of hypoxia-induced PASMC proliferation and provide insight into the therapeutic value of RBPs for vascular diseases.

Methylated miRNAs may serve as potential biomarkers and therapeutic targets for hidradenitis suppurativa.

Hidradenitis suppurativa (HS) is a chronic inflammatory disease influenced by genetics, non-genetic and environmental factors that modulate miRNA expression. Currently, no miRNA data are available for HS. In this study, we profiled DNA methylation patterns of miRNA genes associated with HS susceptibility. Identify miRNA gene methylation profiles associated with HS susceptibility. This study examined the methylation patterns of DNAs from 24 healthy controls and 24 patients with HS using Illumina Infinium MethylationEPIC BeadChip array analysis. Methylation patterns of miRNA genes were analysed using KEGG pathway analysis to explore the inversely correlated pathways regulated by miRNAs. We identified 60 CpG sites representing 65 unique microRNA genes including 54 hypomethylated and 6 hypermethylated CpGs as potentially associated with HS. Some of these CpGs were found to be critical for skin function, such as miR-29, miR-200, miR-205, miR-548 and miR-132. The miR-192 is implicated in non-alcoholic fatty liver disease. The miR-200c gene was identified as a vital determinant in regulating skin repair after injury and may contribute to age-associated alterations in wound repair. miR-132 was significantly upregulated during the inflammation phase of wound repair, enhancing the activity of STAT3 and ERK pathways that promote keratinocyte proliferation. Epigenetically altered microRNA genes are implicated in wound healing, inflammation, keratinocyte proliferation and wound modulation. This is the first study to analyse methylation profiles of miRNA genes in the HS population, highlighting the unique role that miRNAs might play in diagnosing and treating HS.

Plasma Exo-miRNAs Correlated with AD-Related Factors of Chinese Individuals Involved in Aβ Accumulation and Cognition Decline

Numerous studies have investigated the risk factors of Alzheimer’s disease (AD); however, AD-risk factors related miRNAs were rarely reported. In this study, AD-risk factor related miRNAs of 105 Chinese individuals (45 AD patients and 60 cognitively normal controls) were investigated. The results showed that Hsa-miR-185-5p, Hsa-miR-20a-5p, and Hsa-miR-497-5p were related to AD and education, Hsa-miR-185-5p, Hsa-miR-181c-5p, Hsa-miR-664a-3p, Hsa-miR-27a-3p, Hsa-miR-451a, and Hsa-miR-320a were related to AD and depression. Target prediction of above miRNAs showed that these miRNAs were involved in the generation and clearance of amyloid-beta (Aβ), important molecules related to cognition, and disease-activated microglia response to AD. It is worth noting that Hsa-miR-185-5p was related to both education and depression, whose decreased expression pattern in AD patients was alleviated by education and enhanced by depression, and participates in Aβ generation and accumulation. Our results indicated that certain education and depression factors can contribute to AD progression by modulating miRNA expression, implying that preventive interventions might alter AD progression in Chinese patients.

Anti-Inflammatory microRNAs for Treating Inflammatory Skin Diseases.

Skin inflammation occurs due to immune dysregulation because of internal disorders, infections, and allergic reactions. The inflammation of the skin is a major sign of chronic autoimmune inflammatory diseases, such as psoriasis, atopic dermatitis (AD), and lupus erythematosus. Although there are many therapies for treating these cutaneous inflammation diseases, their recurrence rates are high due to incomplete resolution. MicroRNA (miRNA) plays a critical role in skin inflammation by regulating the expression of protein-coding genes at the posttranscriptional level during pathogenesis and homeostasis maintenance. Some miRNAs possess anti-inflammatory features, which are beneficial for mitigating the inflammatory response. miRNAs that are reduced in inflammatory skin diseases can be supplied transiently using miRNA mimics and agomir. miRNA-based therapies that can target multiple genes in a given pathway are potential candidates for the treatment of skin inflammation. This review article offers an overview of the function of miRNA in skin inflammation regulation, with a focus on psoriasis, AD, and cutaneous wounds. Some bioactive molecules can target and modulate miRNAs to achieve the objective of inflammation suppression. This review also reports the anti-inflammatory efficacy of these molecules through modulating miRNA expression. The main limitations of miRNA-based therapies are rapid biodegradation and poor skin and cell penetration. Consideration was given to improving these drawbacks using the approaches of cell-penetrating peptides (CPPs), nanocarriers, exosomes, and low-frequency ultrasound. A formulation design for successful miRNA delivery into skin and target cells is also described in this review. The possible use of miRNAs as biomarkers and therapeutic modalities could open a novel opportunity for the diagnosis and treatment of inflammation-associated skin diseases.

Withaferin A mediated changes of miRNA expression in breast cancer-derived mammospheres.

Breast cancer is a heterogeneous disease consisting of atypical cell populations that share stem cell-like characteristics associated with therapeutic resistance, disease relapse, and poor clinical outcome. MicroRNAs (miRNA),and small noncoding RNA, are pivotal in the regulation of self-renewal, stemness, and cellular differentiation. Withaferin A (WA), a steroidal lactone, is a major bioactive constituent of Withania somnifera (Solanaceae) known for its anticancer properties. In this study, the effect of WA on modulation of miRNA expression in breast cancer-derived mammosphere was assessed utilizing small RNA sequencing. Treatment with WA inhibited MCF-7 and T47D cells derived mammosphere formation with a significant decrease in CD44, EpCAM, Nanog, OCT4, and SOX2 as markers of self-renewal and stemness. Small RNA sequencing demonstrated a total of 395 differentially expressed miRNAs (DEMs) including 194 upregulated and 201 downregulated miRNAs in WA-treatedMCF-7 mammospheres. Bioinformatics analysis utilizing theKEGG pathway, Gene Ontology enrichment, protein-protein, and miRNA-mRNA interaction network identified altered expression in a few hub genes viz.AKT1, PTEN, MYC, CCND1,VEGFA,NOTCH1, andIGFR1associated with DEMs in WA-treatedmammospheres. Further quantitativeRT-PCR analysis validated the expression of DEMs including miR-549a-5p, miR-1247-5p, miR-124-5p, miR-137-5p, miR-34a-5p, miR-146a-5p, miR-99a-5p, miR-181a-5p, let-7c-5p, and let-7a-5p. In particular, let-7c-5p is designated as a tumor suppressor in breast cancer. An increase in miR-let-7c-5p expression was noted after WA treatment, with a simultaneous decrease in CCND1 and c-MYC at mRNA and protein levels. Taken together, our study demonstrated WA-mediated miRNA expression, in particular, upregulation of miR-let-7c-5p, leads to the inhibition of breast cancer cells derived mammospheres.

Angiotensin (1-7) protects against renal ischemia-reperfusion injury via regulating expression of NRF2 and microRNAs in Fisher 344 rats.

Ischemia-reperfusion (I/R) is considered the primary cause of acute kidney injury and is higher among older individuals. Although ischemic episodes are hard to predict and prevent, detrimental ischemic effects could be mitigated by exogenous intervention. This study aimed to identify the protective role of angiotensin (1-7) [ANG(1-7)] against I/R-induced renal injury in adult versus aged rats. Adult and aged male Fisher 344 rats were subjected to 40 min of bilateral renal ischemia followed by 28 days of reperfusion. ANG(1-7) was administered intraperitoneally in ischemic rats for 28 days with or without the Mas receptor antagonist A779. I/R increased blood pressure, plasma creatinine, urinary 8-isoprostane, and renal infiltration of pro- and anti-inflammatory macrophages and reduced glomerular filtration rate in both adult and aged rats compared with sham rats. In addition to causing glomerular sclerosis and tubular damage, I/R increased the expression of the following pathogenic miRNAs: miR-20a-5p, miR-21-5p, miR-24-3p, and miR-194-5p in both age groups. ANG(1-7) treatment of ischemic rats mitigated oxidative stress and renal inflammation, restored renal structure and function, and reduced high blood pressure. Also, ANG(1-7) suppressed the expression of pathogenic miRNAs. In addition, ANG(1-7) treatment of I/R rats increased the expression of the redox-sensitive transcription factor nuclear factor-erythroid factor 2-related factor 2 (NRF2) and phase II antioxidant enzymes. The beneficial effects of ANG(1-7) were sensitive to A779. Collectively, these data suggest that ANG(1-7) associated with NRF2 activation could alleviate post-I/R-induced kidney injury, and therefore serve as a potential therapeutic compound to protect against biochemical and morphological pathologies of I/R in both adults and aged populations.NEW & NOTEWORTHY This is the first study to show that ANG(1-7) via Mas receptors could activate the redox-sensitive nuclear factor-erythroid factor 2-related factor 2 (NRF2)-phase II antioxidant system and protect against ischemia-reperfusion (I/R)-induced renal injury, identifying ANG(1-7), Mas receptor agonists, or NRF2 activators as potential therapeutic interventions to protect against renal and cardiovascular diseases. Moreover, miRNAs have differential expression in adult versus aged rats, and I/R modulates miRNA expression in both age groups, indicating their involvement in kidney disease.

Impacts of MicroRNAs Induced by the Gut Microbiome on Regulating the Development of Colorectal Cancer.

Although a dysfunctional gut microbiome is strongly linked to colorectal cancer (CRC), our knowledge of the mediators between CRC and the microbiome is limited. MicroRNAs (miRNAs) affect critical cellular processes, such as apoptosis, proliferation, and differentiation, and contribute to the regulation of CRC progression. Increasingly, studies found that miRNAs can significantly mediate bidirectional interactions between the host and the microbiome. Notably, miRNA expression is regulated by the gut microbiome, which subsequently affects the host transcriptome, thereby influencing the development of CRC. This study typically focuses on the specific functions of the microbiome in CRC and their effect on CRC-related miRNA production and reviews the role of several bacteria on miRNA, including Fusobacterium nucleatum, Escherichia coli, enterotoxigenic Bacteroides fragilis, and Faecalibacterium prausnitzii. Based on the important roles of miRNAs and the gut microbiome in CRC, strategies for modulating miRNA expression and regulating the gut microbiome composition need to be applied, such as bioactive dietary components and fecal microorganism transplantation.