microRNA Expression Profiles Research Articles

MicroRNA expression profiling of cutaneous squamous cell carcinomas and precursor lesions

AbstractBackgroundActinic keratoses (AK) are pre‐malignant skin lesions caused by chronic sun exposure. Progression from an AK to intraepidermal carcinoma (IEC) and a cutaneous squamous cell carcinoma (SCC) is well known but the rate of transformation to an invasive SCC is highly variable. Since no definitive biomarkers are available, treatment decisions are made ad hoc.ObjectivesTo fully characterise our AK to SCC progression series, we performed microRNA (miRNA) microarray expression profiling of normal and photodamaged skin, as well as AKs, IEC, and invasive SCCs.MethodsThe study recruited 27 patients who donated fresh biopsies of normal skin, photodamaged skin, AK, IEC, and SCC (n = 67 specimens). All miRbase (v.21) miRNAs were profiled to identify miRNAs related to SCC progression. miRNAs were validated using qRT‐PCR and in vitro phenotypic assays.ResultsThere were 234 robustly expressed miRNAs across the tissue collection, which resulted in 20 miRNA that were differentially expressed ((cor)p ≤ 0.05 and ≥ 10 fold) between normal skin and SCC. Hierarchical clustering all samples illustrated that AKs, IEC, and SCCs were largely indistinguishable, which confirms the premalignant status of an AK. A panel of miRNAs showed significant dysregulation between normal and photodamaged skin and AK. Importantly, we found miR‐34a‐5p and miR‐31‐5p had significant differential expression between AKs and IEC and IEC and SCC respectively. Phenotypic assays determined that the miR‐31 duplex had opposing effects on SCC cell lines which suggests that dysregulation of this duplex may be related to the dynamic control of progression of transformed keratinocytes.ConclusionsThis study confirmed the continuum of AK with IEC and SCC highlighting that miRNA expression plays a role in keratinocyte transformation. Development of our putative miRNA biomarker candidates is warranted to aid in clinical management of patients experiencing high AK load to determine the most appropriate treatment.

MicroRNA expression profiling of urine exosomes in children with congenital cytomegalovirus infection

Congenital cytomegalovirus (cCMV) infection can damage the central nervous system in infants; however, its prognosis cannot be predicted from clinical evaluations at the time of birth. Urinary exosomes can be used to analyze neuronal damage in neuronal diseases. To investigate the extent of neuronal damage in patients with cCMV, exosomal miRNA expression in the urine was investigated in cCMV-infected infants and controls. Microarray analysis of miRNA was performed in a cohort of 30 infants, including 11 symptomatic cCMV (ScCMV), 7 asymptomatic cCMV (AScCMV), and one late-onset ScCMV cases, and 11 healthy controls (HC). Hierarchical clustering analysis revealed the distinct expression profile of ScCMV. The patient with late-onset ScCMV was grouped into the ScCMV cluster. Pathway enrichment analysis of the target mRNAs differed significantly between the ScCMV and HC groups; this analysis also revealed that pathways related to brain development were linked to upregulated pathways. Six miRNAs that significantly different between groups (ScCMV vs. HC and ScCMV vs. AScCMV) were selected for digital PCR in another cohort for further validation. Although these six miRNAs seemed insufficient for predicting ScCMV, expression profiles of urine exosomal miRNAs can reveal neurological damage in patients with ScCMV compared to those with AcCMV or healthy infants.

MicroRNA Expression Profile in Early-Stage Breast Cancers.

Breast cancer is one of the leading causes of cancer deaths in women. Early diagnosis offers the best hope for a cure. Ductal carcinoma in situ is considered a precursor of invasive ductal carcinoma of the breast. In this study, we carried out microRNA sequencing from 7 ductal carcinoma in situ (DCIS), 6 infiltrating ductal carcinomas (IDC Stage IIA) with paired normal, and 5 unpaired normal breast tissue samples. We have deployed miRge for microRNA analysis, DESeq for differential expression analysis, and Cytoscape for competing endogenous RNA network investigation. Here, we identified 76 miRNAs that were differentially expressed in DCIS and IDC. Additionally, we provide preliminary evidence of miR-365b-3p and miR-7-1-3p being overexpressed, and miR-6507-5p, miR-487b-3p, and miR-654-3p being downregulated in DCIS relative to normal breast tissue. We also identified a miRNA miR-766-3p that was overexpressed in earlystage IDCs. The overexpression of miR-301a-3p in DCIS and IDC was confirmed in 32 independent breast cancer tissue samples. Higher expression of miR-301a-3p is associated with poor overall survival in The Cancer Genome Atlas Breast Cancer (TCGA-BRCA) dataset, indicating that it may be associated with DCIS at high risk of progressing to IDC and warrants deeper investigation.

MicroRNAs as Potential Biomarkers of Mental Disorders: Diagnostic and Prognostic Implications

Background: microRNAs are small non-coding RNAs that play a crucial role in post-transcriptional regulation of gene expression. Recent studies indicate the involvement of microRNAs in the pathogenesis of various psychiatric disorders, which allows to consider them as diagnostic biomarkers and therapeutic targets.The aim of this literature review is to analyse curren research on the involvement of microRNAs in the formation of psychiatric disorders, focusing on their potential as diagnostic and prognostic biomarkers. Materials and methods: to find relevant publications, we searched eLibrary and PubMed databases using the following keywords and terms: microRNAs, mental disorders, psychological status, biomarkers, diagnosis, prognosis.Conclusion: numerous studies suggest that microRNAs are involved in the regulation of critical molecular pathways associated with psychiatric disorders, including neurotransmission, neurodevelopment, and synaptic plasticity. Dysregulation of certain microRNAs has been observed in various psychiatric disorders such as major depressive disorder, schizophrenia, bipolar disorder, anxiety disorders, autism spectrum disorders, attention-deficit/hyperactivity disorder and addictive disorders. It is highlighted that the investigated microRNAs have a high potential to be used as diagnostic biomarkers, opening up possibilities for early detection and personalised treatment strategies. The identification of specific microRNAs associated with different psychiatric disorders offers new opportunities to develop innovative diagnostic approaches and targeted therapeutic interventions. However, a number of challenges remain, including differences in microRNA expression levels and profiles due to the heterogeneity of psychiatric disorders, the need for standardisation of microRNA analysis protocols and their further validation in large-scale studies on different patient populations. Collaborative efforts between basic genetics researchers and clinicians are needed to harness the full potential of microRNA analysis for the diagnosis and treatment of psychiatric disorders.

Differential Expression of Down-regulated MicroRNA-126 and Micro RNA-22 in Ovarian Carcinogenesis

Background: Non-coding RNA i.e. MicroRNA plays an important role in the progression and pathogenesis of different types of tumours including ovarian cancer. Deregulated microRNA expression could transform the passivity of cancer, disease progression, chemoresistance, and mobility. The miRNA profile of healthy and cancerous samples was observed to be different. MicroRNA expression analysis and profiling have a bright future in improving the effectiveness of ovarian cancer treatment that is customized to the patient's specific requirements. Expression analysis of serum microRNA-126 and microRNA-22 in ovarian carcinogenesis has been done in the present study. Methods: Present study has been done in the serum of eighty- two epithelial ovarian cancer patients and eighty- two their age-matched healthy women to investigate +the expression of miR-126 and miR22 was TaqMan PCR microRNA assay. The correlation of expression miR-126 and miR-22 with epidemiological and clinicopathological factors was determined statistically. Results: Results showed a 3.37-fold decrease in miR-126 expression and a 2.67-fold reduction in miR-22 expression in ovarian cancer patients. Decreased serum level of miR-22 and miR-126 in ovarian cancer patients has been correlated with the FIGO stage. Results revealed 87.46 sensitivity and 91.12 specificities for down-regulated microRNA 22 with FIGO stage of ovarian cancer and 71.26 sensitivity and 81.12 specificities respectively. More sensitivity and specificity of microRNA 22 with FIGO stage of ovarian cancer was revealed as compared to microRNA 126. Conclusion: Present study revealed downregulated expression of miR-126 and miR-22 in the serum of epithelial ovarian cancer patients. Among all epidemiological and clinical parameters, the FIGO stage of ovarian cancer revealed a substantial association with microRNA level. Results revealed that the sensitivity and specificity of down-regulated microRNA 22 in ovarian cancer were 87.46 and 91.12 and for microRNA 126 with 71.26 and 81.12 respectively. This may be investigated and verified as a durable diagnostic biomarker for the pre-diagnosis of ovarian carcinogenesis.

Major approaches of inflammatory processes and peri-implant infections in the cellular and molecular scenario of mesenchymal stem cells, exosomes, and microRNAs: a systematic review

Introduction: Bone diseases are denoted by fractures, osteoporosis, and osteoarthritis that affect a large number of individuals, with a rising prevalence of osteopenia for 64.3 million American individuals and osteoporosis for 11.9 million by the year 2030. Dental implants are not free from possible complications with consequent failure, the causes of which are still the subject of debate in the dental scientific community. In particular, peri-implant infections are multifactorial pathological conditions characterized by inflammation of the peri-implant mucosa with or without progressive loss of supporting bone. Specific expression profiles of microRNAs (miRNAs) extracted from peri-implant tissues are predictive of specific clinical outcomes of dental implants and can be used as biomarkers in implant dentistry for diagnostic and prognostic purposes. Objective: It was to address the main approaches to inflammatory processes and peri-implant infections and dental implants in the cellular and molecular scenarios of mesenchymal stem cells, exosomes, and microRNAs, emphasizing the main biomarkers in the therapeutic control of harmful dental implant processes. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from October 2023 to January 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: A total of 138 articles were found, 44 articles were evaluated in full and 34 were included and developed in the present systematic review study. Considering the Cochrane tool for risk of bias, the overall assessment resulted in 26 studies with a high risk of bias and 24 studies that did not meet GRADE and AMSTAR-2. Most studies did not show homogeneity in their results, with X2=67.9%>50%. It was concluded that specific expression profiles of miRNAs extracted from peri-implant tissues are predictive of specific clinical outcomes of dental implants and can be used as biomarkers in implant dentistry for diagnostic and prognostic purposes. Studies have shown that many of the miRNAs extracted from the implant's peri-crevicular fluid were common to those detected in soft tissues taken from the same peri-implant sites. Evidence suggests that exosomes derived from adipose-derived stem cells exhibit similar functions to those cells, with low immunogenicity and no tumorization. Insufficient bone volume directly impacts the placement of dental implants. Adipose-derived stem cells can accelerate bone healing when combined with dental implants. An increase in the concentration of exosomes with negative expression of miRNA-21-3p and miRNA-150-5p may be related to the development of peri-implantitis.

Circulating miRNA’s biomarkers for early detection of hepatocellular carcinoma in Egyptian patients based on machine learning algorithms

Liver cancer, which ranks sixth globally and third in cancer-related deaths, is caused by chronic liver disorders and a variety of risk factors. Despite therapeutic improvements, the prognosis for Hepatocellular Carcinoma (HCC) remains poor, with a 5-year survival rate for advanced cases of less than 12%. Although there is a noticeable decrease in the frequency of cases, liver cancer remains a significant worldwide health concern, with estimates surpassing one million cases by 2025. The prevalence of HCC has increased in Egypt, and it includes several neoplasms with distinctive messenger RNA (mRNA) and microRNA (miRNA) expression profiles. In HCC patients, certain miRNAs, such as miRNA-483-5P and miRNA-21, are upregulated, whereas miRNA-155 is elevated in HCV-infected people, encouraging hepatocyte proliferation. Short noncoding RNAs called miRNAs in circulation have the potential as HCC diagnostic and prognostic markers. This paper proposed a model for examining circulating miRNAs as diagnostic and predictive markers for HCC in Egyptian patients and their clinical and pathological characteristics. The proposed HCC detection model consists of three main phases: data preprocessing phase, feature selection based on the proposed Binary African Vulture Optimization Algorithm (BAVO) phase, and finally, classification as well as cross-validation phase. The first phase namely the data preprocessing phase tackle the main problems associated with the adopted datasets. In the feature selection based on the proposed BAVO algorithm phase, a new binary version of the BAVO swarm-based algorithm is introduced to select the relevant markers for HCC. Finally, in the last phase, namely the classification and cross-validation phase, the support vector machine and k-folds cross-validation method are utilized. The proposed model is evaluated on three studies on Egyptians who had HCC. A comparison between the proposed model and traditional statistical studies is reported to demonstrate the superiority of using the machine learning model for evaluating circulating miRNAs as diagnostic markers of HCC. The specificity and sensitivity for differentiation of HCC cases in comparison with the statistical-based method for the first study were 98% against 88% and 99% versus 92%, respectively. The second study revealed the sensitivity and specificity were 97.78% against 90% and 98.89% versus 92.5%, respectively. The third study reported 83.2% against 88.8% and 95.80% versus 92.4%, respectively. Additionally, the results show that circulating miRNA-483-5p, 21, and 155 may be potential new prognostic and early diagnostic biomarkers for HCC.

MicroRNA Expression Profile in Obesity-Induced Kidney Disease Driven by High-Fat Diet in Mice.

Obesity is one of the main causes of chronic kidney disease; however, the precise molecular mechanisms leading to the onset of kidney injury and dysfunction in obesity-associated nephropathy remain unclear. The present study aimed to unveil the kidney microRNA (miRNA) expression profile in a model of obesity-induced kidney disease in C57BL/6J mice using next-generation sequencing (NGS) analysis. High-fat diet (HFD)-induced obesity led to notable structural alterations in tubular and glomerular regions of the kidney, increased renal expression of proinflammatory and profibrotic genes, as well as an elevated renal expression of genes involved in cellular lipid metabolism. The miRNA sequencing analysis identified a set of nine miRNAs differentially expressed in the kidney upon HFD feeding, with miR-5099, miR-551b-3p, miR-223-3p, miR-146a-3p and miR-21a-3p showing the most significant differential expression between standard diet (STD) and HFD mice. A validation analysis showed that the expression levels of miR-5099, miR-551b-3p and miR-146a-3p were consistent with NGS results, while Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analyses revealed that these three validated miRNAs modulated target genes involved in metabolic and adipocytokine pathways, fatty acid and lipid metabolism, and inflammatory, senescence and profibrotic pathways. Our results suggest that differentially expressed miRNAs play pivotal roles in the intricate pathophysiology of obesity-associated kidney disease and could potentially create novel treatment strategies to counteract the deleterious effects of obesity on kidney function.

Comprehensive Analysis of circRNA, lncRNA, miRNA and mRNA Expression Profiles and Their Competing Endogenous RNA Networks in Hepatitis B Virus-Related Hepatocellular Carcinoma.

Pursuing knowledge about circular RNA (circRNA), long non-coding RNA (lncRNA), microRNA (miRNA), and messenger RNA (mRNA) expression profiles and their competing endogenous RNA (ceRNA) networks in hepatitis B virus-related hepatocellular carcinoma (HBV-related HCC) was the focus of this research. Expression patterns of circRNAs, lncRNAs, miRNAs, and mRNAs were searched for in relation to HBV-related HCC using whole-transcriptome sequencing. The expression levels of chosen circRNA, lncRNA, miRNA, and mRNA were analyzed using quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The potential connections and roles of ceRNA were deduced via bioinformatics research. The sum of 284 circRNAs, 2,927 lncRNAs, 693 miRNAs, and 5566 mRNAs were discovered to be expressed at considerably different levels in HBV-related HCC tissue and adjacent normal tissue. And the most significantly up- and down-regulated circRNAs, lncRNAs, miRNAs, and mRNAs were verified in HBV-related HCC by qRT-PCR. The circRNA/miRNA/mRNA and lncRNA/miRNA/mRNA networks of HBV-related HCC were established, and the ceRNA regulatory networks revealed the gene expression mechanisms controlled by ncRNAs. Collectively, we revealed the contribution of various circRNA, lncRNA, miRNA, and mRNA expression profiles and identified their ceRNA regulatory networks in HBV-related HCC, providing a theoretical basis for further exploration.

Psychosocial Stress and MicroRNA Expression Profiles in Myometrial Tissue of Women Undergoing Surgical Treatment for Uterine Fibroids.

Uterine leiomyomas (fibroids) are the most common non-cancerous tumors affecting women. Psychosocial stress is associated with fibroid risk and severity. The relationship between psychosocial stress and fibroid pathogenesis may involve alterations in microRNAs (miRNAs) although this has yet to be examined. We investigated associations between two psychosocial stress measures, a composite measure of recent stressful life events and perceived social status, with expression levels of 401 miRNAs in myometrium (n = 20) and fibroids (n = 44; 20 with paired fibroid and myometrium samples) among pre-menopausal women who underwent surgery for fibroid treatment. We used linear regressions to identify psychosocial stressors associated with miRNAs, adjusting for covariates (age, body mass index, race/ethnicity, and oral contraceptive use). The association between psychosocial stressors and miRNAs was considered statistically significant at an FDR p < 0.10 and showed a monotonic response (nominal p-trend < 0.05). In the myometrium, 21 miRNAs were significantly associated with a composite measure of recent stressful events, and two miRNAs were associated with perceived social status. No fibroid miRNAs were associated with either stress measure. Pathway analyses revealed miRNA-mRNA targets were significantly enriched (FDR p < 0.05) in pathways relevant to cancer/tumor development. Of the 74 differentially expressed miRNAs between myometrium and fibroids, miR-27a-5p and miR-301b were also associated with stress exposure. Our pilot analysis suggests that psychosocial stress is associated with myometrial miRNA expression and, thus, may have a role in the pathogenesis of fibroids from healthy myometrium.

Gene Ex Vivo Transduction Effects on Flap Survival and MicroRNAs Expression Analysis in Rat Allotransplantation Model

The lack of noninvasive biomarkers for graft rejection remains a challenge for the accurate monitoring of vascularized composite allotransplants. Viral vector-mediated gene transfer is a promising method for preventing graft rejection. In this study, we aimed to establish the expression profile of microRNAs (miRNAs) in skin flap allotransplantation, with or without gene transfer, and determine the potential role of several miRNAs as biomarkers of acute rejection and immune tolerance. An abdominal epigastric flap was transplanted from SD (RT1a) to Wistar rats (RT1Au). The adenoviral interleukin 10 (vIL-10) gene was transferred to the experimental group via flap pedicle injection. Postoperatively, flap appearance, hematoxylin and eosin staining, immunohistochemical staining, and miRNA expression analyses were performed. The viral IL-10 gene-treated group showed improved flap survival and reduced acute rejection response compared with the control group. On postoperative day 7, IL-10 expression in the flap was identified using immunohistochemistry and real-time polymerase chain reaction. The expression of miR-191a, miR-31a, miR-16, and miR-3473 was upregulated in the skin tissue, and that of miR-484, miR-132, miR-139, miR-150, and miR-6216 was upregulated in the serum. AV IL-10 gene transfer could be an effective immunosuppressive strategy for the prevention of skin flap allograft rejection. Additionally, some miRNAs were upregulated in the experimental group, serving as potential biomarkers of immune tolerance.

Expression of microRNAs related to apoptosis in the aqueous humor and lens capsule of patients with glaucoma.

The aim of this study is to investigate the expression profiles of microRNAs (miRNAs) related to apoptosis in the aqueous humor (AH) and lens capsule (LC) of patients with glaucoma. AH and LC samples were collected from patients with open-angle glaucoma and control participants who were scheduled for cataract surgery. A miRNA PCR array comprising 84 miRNAs was used to analyze the AH (glaucoma, n = 3; control, n = 3) and LC samples (glaucoma, n = 3; control, n = 4). Additionally, the AH and LC samples (glaucoma, n = 3; control, n = 4) were subjected to quantitative real-time PCR to validate the differentially expressed miRNAs determined using the PCR array. Bioinformatics analysis was performed to identify the interactions between miRNAs and diseases. Additionally, the differential expression of these miRNAs and the target gene was validated through in vitro experiments using a retinal ganglion cell (RGC) model. Expression levels of 19 and 3 miRNAs were significantly upregulated in the AH and LC samples of the glaucoma group, respectively (p < 0.05). Of these, the expression levels of hsa-miR-193a-5p and hsa-miR-222-3p showed significant differences in both AH and LC samples. Bioinformatics analysis showed experimentally validated 8 miRNA:gene pairs. Among them, PTEN was selected to analyze the expression level in AH and LC from separate cohort (glaucoma, n = 5; control, n = 4). The result showed downregulation of PTEN concurrent with upregulation of the two miRNAs in LC samples of glaucoma group. In vitro experiments validated that the expression levels of hsa-miR-193a-5p and hsa-miR-222-3p were significantly upregulated, and that of PTEN was significantly downregulated in the H2O2-treated RGC, while the level of PTEN was recovered through co-treatment with miR-193a inhibitor or miR-222 inhibitor. This is the first study to investigate the differential expression of apoptosis-related miRNAs in the AH and LC of patients with glaucoma. Hsa-miR-193a-5p and hsa-miR-222-3p, which were upregulated in both AH and LC, may be considered potential biomarkers for glaucoma.

Integrated analysis of microRNA and messenger RNA expression profiles reveals functional microRNA in infectious bovine rhinotracheitis virus-induced mitochondrial damage in Madin-Darby bovine kidney cells

BackgroundStudies have confirmed that Infectious bovine rhinotracheitis virus (IBRV) infection induces mitochondrial damage. MicroRNAs (miRNAs) are a class of noncoding RNA molecules, which are involved in various biological processes and pathological changes associated with mitochondrial damage. It is currently unclear whether miRNAs participate in IBRV-induced mitochondrial damage in Madin-Darby bovine kidney (MDBK) cells.ResultsIn the present study, we used high-throughput sequencing technology, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis to screen for mitochondria-related miRNAs and messenger RNAs (mRNAs). In total, 279 differentially expressed miRNAs and 832 differentially expressed mRNAs were identified in 6 hours (IBRV1) versus 24 hours (IBRV2) after IBRV infection in MDBK cells. GO and KEGG enrichment analysis revealed that 42 differentially expressed mRNAs and 348 target genes of differentially expressed miRNAs were correlated with mitochondrial damage, and the miRNA-mitochondria-related target genes regulatory network was constructed to elucidate their potential regulatory relationships. Among the 10 differentially expressed miRNAs, 8 showed expression patterns consistent with the high-throughput sequencing results. Functional validation results showed that overexpression of miR-10a and miR-182 aggravated mitochondrial damage, while inhibition of miR-10a and miR-182 alleviated mitochondrial damage.ConclusionsThis study not only revealed the expression changes of miRNAs and mRNAs in IBRV-infected MDBK cells, but also revealed possible biological regulatory relationship between them. MiR-10a and miR-182 may have the potential to be developed as biomarkers for the diagnosis and treatment of IBRV. Together, Together, these data and analyses provide additional insights into the roles of miRNA and mRNA in IBRV-induced mitochondria damage

Gene expression profile of mitogen-activated kinases and microRNAs controlling their expression in HaCaT cell culture treated with lipopolysaccharide A and cyclosporine A

ABSTRACT Studies indicate that mitogen-activated protein kinases (MAPKs) are activated and overexpressed in psoriatic lesions. The aim of the study was to assess changes in the expression pattern of genes encoding MAPKs and microRNA (miRNA) molecules potentially regulating their expression in human adult low-calcium high-temperature (HaCaT) keratinocytes exposed to bacterial lipopolysaccharide A (LPS) and cyclosporine A (CsA). HaCaT cells were treated with 1 µg/mL LPS for 8 h, followed by treatment with 100 ng/mL cyclosporine A for 2, 8, or 24 h. Untreated cells served as controls. The molecular analysis consists of microarray, quantitative real-time polymerase chain reaction, and enzyme-linked immunosorbent assay analyses. The statistical analysis of the obtained results was performed using Transcriptome Analysis Console and STATISTICA 13.5 PL with the statistical significance threshold of p < 0.05. Changes in the expression profile of six mRNAs: dual-specificity phosphatase 1 (DUSP1), dual-specificity phosphatase 4 (DUSP4), mitogen-activated protein kinase kinase 2 (MAP2K2), mitogen-activated protein kinase kinase 7 (MAP2K7), mitogen-activated protein kinase kinase kinase 2 (MAP3K2) and mitogen-activated protein kinase 9 (MAPK9) in cell culture exposed to LPS or LPS and the drug compared to the control. We observed that under the LPS and cyclosporine treatment, the expression o/ miR-34a, miR-1275, miR-3188, and miR-382 changed significantly (p < 0.05). We demonstrated a potential relationship between DUSP1 and miR-34a; DUSP4 and miR-34a, miR-382, and miR-3188; MAPK9 and miR-1275, MAP2K7 and mir-200-5p; MAP3K2 and mir-200-5p, which may be the subject of further research in the context of psoriasis.

Exploring the expression and clinical significance of the miR-140-3p-HOXA9 axis in colorectal cancer

PurposeThis study aims to investigate the expression patterns and clinical significance of miR-140-3p and homeobox A9 (HOXA9) in colorectal cancer (CRC) selected by bioinformatic study, while elucidating their potential interplay.MethodsThe microRNA expression profiles of paired colorectal cancer and matched normal tissues were retrieved from the Gene Expression Omnibus Database. Differentially expressed microRNAs and microRNA candidates were filtered and subjected to further analysis. Clinicopathological data, along with paraffin-embedded samples of colorectal tumor tissues were collected to facilitate comprehensive analysis. Expression levels of miR-140-3p and HOXA9 were quantified using qRT-PCR and immunohistochemistry. Survival rates were determined using the Kaplan–Meier method, and the COX regression model was utilized to identify independent prognostic factors that impact the overall prognosis.ResultsMiR-140-3p was significantly downregulated in colorectal tumors compared to normal tissue, and HOXA9 was identified as a previously unreported potential downstream target. HOXA9 expression was elevated in tumors compared to normal tissues. Reduced miR-140-3p expression was associated with lymph node metastasis, while high HOXA9 expression correlated with both lymph node metastasis and lympho-vascular invasion. Patients with low miR-140-3p and high HOXA9 expression had a poorer prognosis. HOXA9 was identified as an independent risk factor for CRC patient survival.ConclusionThe miR-140-3p-HOXA9 signaling disruption is closely linked to lymph node metastasis and unfavorable prognosis in CRC. This axis shows promise as a clinical biomarker for predicting the CRC patient survival and a potential therapeutic target.

Differential expression of tsRNAs and miRNAs in embryo culture medium: potential impact on embryo implantation.

Can small RNA derived from embryos in conditioned embryo culture medium (ECM) influence embryo implantation? We employed small RNA sequencing to investigate the expression profiles of transfer RNA-derived small RNA (tsRNA) and microRNA (miRNA) in ECM from high-quality and low-quality embryos. Quantitative real-time PCR was employed to validate the findings of small RNA sequencing. Additionally, we conducted bioinformatics analysis to predict the potential functions of these small RNAs in embryo implantation. To establish the role of tiRNA-1:35-Leu-TAG-2 in embryonic trophoblast cell adhesion, we utilized co-culture systems involving JAR and Ishikawa cells. Our analysis revealed upregulation of nine tsRNAs and four miRNAs in ECM derived from high-quality embryos, whereas 37 tsRNAs and 12 miRNAs exhibited upregulation in ECM from low-quality embryos. The bioinformatics analysis of tsRNA, miRNA, and mRNA pathways indicated that their respective target genes may play pivotal roles in both embryo development and endometrial receptivity. Utilizing tiRNA mimics, we demonstrated that the prominently expressed tiRNA-1:35-Leu-TAG-2 in the low-quality ECM group can be internalized by Ishikawa cells. Notably, transfection of tiRNA-1:35-Leu-TAG-2 into Ishikawa cells reduced the attachment rate of JAR spheroids. Our investigation uncovers significant variation in the expression profiles of tsRNAs and miRNAs between ECM derived from high- and low-quality embryos. Intriguingly, the release of tiRNA-1:35-Leu-TAG-2 by low-quality embryos detrimentally affects embryo implantation and endometrial receptivity. These findings provide fresh insights into understanding the molecular foundations of embryo-endometrial communication.

Endogenously Gated DNA Walking Machine for Prescreened MicroRNA Detection in Extracellular Vesicles.

Tumor-derived extracellular vesicle (T-EV) microRNAs have been investigated as promising biomarkers in clinical diagnosis as well as disease progression monitoring. However, the expression profiles of microRNA in different tissues vary widely, the precise monitoring of microRNA levels in EVs originating from diseased tissues is susceptible to background interference, thus remains a challenge. Conventional assays require extensive processing, such as EV isolation and even sample lysis, which is both slow and laborious, and the cumbersome pretreatment could spoil the downstream analysis. To address this issue, we developed a generalizable strategy for T-EVs-selective activation and therefore specific amplified microRNA imaging. The conditional signal amplification is established by integrating a traditional DNA walker system with endogenously activated motif to achieve sensitized microRNA imaging in T-EVs. The preorganized endogenous activation with additional sensing criteria narrowed the scope against the complex specimens, and the amplified sensing with reduced off-target signals was supposed to be sensitive to monitor the tiny changes of microRNA expression during the disease course, which holds great potential for accurate diagnosis and prognosis.

Urinary Exosomal miR-17-5p Accelerates Bladder Cancer Invasion by Repressing its Target Gene ARID4B and Regulating the Immune Microenvironment

BackgroundUrothelial bladder cancer (BCa) is a common malignant tumor of the urinary system. It has been identified that exosomal miRNAs contribute to the development of BCa. However, its significance and mechanism in the malignant biological behavior of BCa remain unclear. In this study, the influence of exosomal miRNAs on BCa progression was investigated. MethodsHigh-throughput sequencing was conducted to analyze the microRNA-expression profile in urinary exosomes to screen out the key miRNA of muscle-invasive bladder cancer (MIBC). Then, candidate miRNA expression was verified and validated in urinary exosomes and tissue samples. To address the potential role of the candidate miRNA, we overexpressed and knocked down the candidate miRNA and explored its activity in BCa cell lines. Furthermore, the target gene of the selected miRNA was predicted and validated. ResultsThe expression profile of miRNAs revealed increased expression of miR-17-5p in MIBC urinary exosomes, and this was later confirmed in urinary exosomes and tissue samples. Cell function studies revealed that exosomal miR-17-5p significantly promoted the growth and invasion of BCa cells. Bioinformatics and luciferase experiments demonstrated that the ARID4B mRNA 3′ UTR might be the binding site for miR-17-5p. Low ARID4B levels were linked to high-grade BCa patients and were associated with a better prognosis. ConclusionElevated miR-17-5p contributes to BCa progression by targeting ARID4B and influencing the immune system. Based on these findings, miR-17-5p has the potential to be a new therapeutic target for the treatment of BCa.

Analyzing of colorectal cancerrelated genes and microRNAs expression profiles in response to probiotics Lactobacillus acidophilus and Saccharomyces cerevisiae in colon cancer cell lines.

Colorectal cancer is the world's third most frequent cancer and the fourth cause of mortality. Probiotics play an important function in preventing metastasis as well as the growth and proliferation of malignant cancer cells. The study investigated the anticancer effect of Lactobacillus acidophilus supernatant and Saccharomyces cerevisiae yeast on colorectal cell lines, including HT29 and SW480 as a colorectal cancer model. The extract from the Lactobacillus acidophilus and Saccharomyces cerevisiae standard probiotics were prepared, and probiotics characterization was confirmed by morphological and Biochemical tests. The viability of HT29 and SW480 colon cancer cell lines on effecting probiotic supernatant was evaluated by measuring the MTT colorimetric method. Comparison of the expression profile of several genes involved in apoptosis, cell cycle, and metastatic pathway in HT29 and SW480 cell lines with the treatment of probiotics extract showed an upregulation in the BAX, CASP3, and CASP9 and down regulation BCl-2, MMP2, and MMP9 genes. Also, a comparison of microRNA expression profiles indicated an increase of miR 34, 135, 25, 16, 195, 27, 98, let7 and a decrease of miR 9, 106b, 17, 21, 155, 221. The findings of this study indicate that probiotics can effectively suppress the proliferation of colorectal cancer cells and even reverse their development. Additionally, the study of cellular genes and miRNA profiles associated with colorectal cancer have demonstrated that our probiotics play a crucial role in CRC prevention by increasing the expression of tumor suppressor microRNAs and their target genes while decreasing oncogenes.

Identification and expression profiling of flowering-related microRNAs and their targets reveals complex regulatory networks associated with bolting time in spinach

Bolting is one of the most important limiting traits in vegetable crops, like spinach, when spurt to flowering before harvesting. The evidence indicates bolting is controlled by various environmental factors including temperature, photoperiod, stresses, and genetic factors such as lncRNAs and miRNAs, but there is no information about miRNA-mediated gene expressions and their roles in flowering-time regulatory networks in spinach. Therefore, to gain more insights into the molecular mechanisms of flowering and bolting, we undertook a comprehensive analysis of miRNAs and their expression profiles in two distinct spinach accessions, namely Kashan (early bolting) and Viroflay (late bolting) by employing cutting-edge high-throughput sequencing technology. Our investigation identified 720 and 750 miRNAs in Kashan and Viroflay, respectively. Remarkably, amid the conserved miRNAs, a convergence of 15 families, exemplified by miR156, miR160, miR164, miR166, miR169, and miR399, renowned for their pivotal roles in flowering/bolting temporal control, was discerned across both accessions. Concerning differentially expressed miRNAs (DEMs), 64 target genes were identified, of which 40 genes were classified into seven flowering-related pathways including age, autonomous, circadian clock, hormone, integrator, photoperiodism, and vernalization. Moreover, novel crosstalks between miRNAs and various flowering-associated genes operating in flowering-related pathways, such as miR156 and squamosa promoter-binding proteins, and miR159 and GAMYB genes in the GA flowering pathway, were identified. Additionally, miR172 influenced MADS-box and AP2-like, while miR319 family, miR164, miR160, and miR169 played distinct roles in modulating key factors associated with flowering processes, including Flowering locus T, FLOWERING PROMOTING FACTOR 1, NAC domain, auxin response factor genes, zinc finger genes, and inorganic phosphate transporter genes, showcasing their intricate regulatory involvement in flowering and bolting pathways. The findings of this study will extend our knowledge of miRNA-mediated flowering modulation and can be used in breeding programs aimed at manipulating the spinach floral regulation system.