Evaluation of circulating microRNA signature in patients with erosive hand osteoarthritis: The HOAmiR study.

OBJECTIVES: To identify circulating micro-RNAs differentially expressed in patients with erosive hand osteoarthritis (HOA) compared to patients with non-erosive HOA and patients without HOA. METHODS: In the screening phase, 768 well-characterized micro-RNAs using Taqman low-density array cards were measured in 30 sera from 10 patients with erosive HOA, 10 patients with non-erosive HOA, and 10 controls without HOA, matched for age and body mass index (BMI). In a second step, we validated the micro-RNAs identified at the screening phase (adjusted p value < 0.05 after false discovery rate correction using Benjamini-Hochberg method and literature review) in larger samples (60 patients with erosive HOA and 60 patients without HOA matched for age and BMI). RESULTS: In the screening phase, we identified 21 down-regulated and 4 up-regulated micro-RNAs of interest between erosive HOA and control groups. Among these, 9 micro-RNAs (miR-373-3p, miR-558, miR-607, miR-653-5p, miR-137 and miR448 were down-regulated, and miR-142-3p, miR-144-3p and miR-34a-5p were up-regulated) were previously described in chondrocytes homeostasis or OA. We found only one significantly down-regulated micro-RNA between erosive and non-erosive HOA. In the validation phase, we showed replication of a single micro-RNA the significant downregulation of miR-196-5p, that had been previously identified in the screening phase among patients with erosive HOA compared to those without HOA. After reviewing the literature and the miRNA-gene interaction prediction model, we found that this microRNA could interact with bone homeostasis and HOXC8, which could explain its role in osteoarthritis. CONCLUSIONS: We found that miR-196-5p was down-regulated in patients with erosive HOA and some of its targets could explain a role in OA.

Application of microRNAs in the diagnosis and monitoring of pediatric germ cell tumors: Kazakh experience.

GCT is characterized by specific biochemical markers expression, such as human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP), which are the main tools in the diagnosis and monitoring of GCT treatment. They are expressed in 15-20% of cases of seminoma and in 60-80% of cases of non-seminoma. MicroRNA profiling allows to identify a number of microRNAs that are superior to classical serum tumor markers in the diagnosis of primary tumors, as well as in subsequent monitoring and prediction of recurrence. We analyzed the expression of 9 microRNAs (microRNA clusters 302/367 and 371-373, microRNA375) in the blood serum of 20 children with extracranial GCT at different stages of therapy and showed their usefulness and informativeness in early detection of events. Taking into consideration the high sensitivity and specificity, serum microRNAs 367,371,372,373,302d are of great interest for clinical use in malignant GCT. Significant expression of miR 375-3p was not detected either in malignant GCT or in teratomas.

Plasma microRNA Signature as Companion Diagnostic for Abiraterone Acetate Treatment in Metastatic Castration-Resistant Prostate Cancer: A Pilot Study.

Abiraterone acetate (AA) serves as a medication for managing persistent testosterone production in patients with metastatic castration-resistant prostate cancer (mCRPC). However, its efficacy varies among individuals; thus, the identification of biomarkers to predict and follow treatment response is required. In this pilot study, we explored the potential of circulating microRNAs (c-miRNAs) to stratify patients based on their responsiveness to AA. We conducted an analysis of plasma samples obtained from a cohort of 33 mCRPC patients before and after three, six, and nine months of AA treatment. Using miRNA RT-qPCR panels for candidate discovery and TaqMan RT-qPCR for validation, we identified promising miRNA signatures. Our investigation indicated that a signature based on miR-103a-3p and miR-378a-5p effectively discriminates between non-responder and responder patients, while also following the drug's efficacy over time. Additionally, through in silico analysis, we identified target genes and transcription factors of the two miRNAs, including PTEN and HOXB13, which are known to play roles in AA resistance in mCRPC. In summary, our study highlights two c-miRNAs as potential companion diagnostics of AA in mCRPC patients, offering novel insights for informed decision-making in the treatment of mCRPC.

Circulating Liquid Biopsy Biomarkers in Glioblastoma: Advances and Challenges.

Gliomas, particularly glioblastoma (GBM), represent the most prevalent and aggressive tumors of the central nervous system (CNS). Despite recent treatment advancements, patient survival rates remain low. The diagnosis of GBM traditionally relies on neuroimaging methods such as magnetic resonance imaging (MRI) or computed tomography (CT) scans and postoperative confirmation via histopathological and molecular analysis. Imaging techniques struggle to differentiate between tumor progression and treatment-related changes, leading to potential misinterpretation and treatment delays. Similarly, tissue biopsies, while informative, are invasive and not suitable for monitoring ongoing treatments. These challenges have led to the emergence of liquid biopsy, particularly through blood samples, as a promising alternative for GBM diagnosis and monitoring. Presently, blood and cerebrospinal fluid (CSF) sampling offers a minimally invasive means of obtaining tumor-related information to guide therapy. The idea that blood or any biofluid tests can be used to screen many cancer types has huge potential. Tumors release various components into the bloodstream or other biofluids, including cell-free nucleic acids such as microRNAs (miRNAs), circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), proteins, extracellular vesicles (EVs) or exosomes, metabolites, and other factors. These factors have been shown to cross the blood-brain barrier (BBB), presenting an opportunity for the minimally invasive monitoring of GBM as well as for the real-time assessment of distinct genetic, epigenetic, transcriptomic, proteomic, and metabolomic changes associated with brain tumors. Despite their potential, the clinical utility of liquid biopsy-based circulating biomarkers is somewhat constrained by limitations such as the absence of standardized methodologies for blood or CSF collection, analyte extraction, analysis methods, and small cohort sizes. Additionally, tissue biopsies offer more precise insights into tumor morphology and the microenvironment. Therefore, the objective of a liquid biopsy should be to complement and enhance the diagnostic accuracy and monitoring of GBM patients by providing additional information alongside traditional tissue biopsies. Moreover, utilizing a combination of diverse biomarker types may enhance clinical effectiveness compared to solely relying on one biomarker category, potentially improving diagnostic sensitivity and specificity and addressing some of the existing limitations associated with liquid biomarkers for GBM. This review presents an overview of the latest research on circulating biomarkers found in GBM blood or CSF samples, discusses their potential as diagnostic, predictive, and prognostic indicators, and discusses associated challenges and future perspectives.

Microarray profiling of serum micro-RNAs in women with Chlamydia trachomatis-associated recurrent spontaneous abortion: A case control study.

Chlamydia trachomatis infection is a major cause of sexually transmitted diseases and adverse pregnancy outcomes such as recurrent spontaneous abortion (RSA). Micro-RNAs (miRNAs) have been known to be upregulated/downregulated in various reproductive-associated diseases such as ectopic pregnancy, preterm birth and pre-eclampsia. However, there is paucity of literature on miRNA profile in C. trachomatis-infected RSA. The present study aimed to determine the profile of serum miRNAs followed by their validation in C. trachomatis-infected RSA and to find target genes involved in biological pathways. Non-heparinized blood and first void urine were collected from 30 non-pregnant women with RSA and 30 non-pregnant women with ≥2 successful deliveries (controls) attending Department of Obstetrics and Gynaecology, Safdarjung hospital, New Delhi, India. C. trachomatis detection was done in urine by PCR and chlamydial load was determined by quantitative real-time PCR (qRT-PCR). miRNA expression was studied by microarray analysis followed by in vitro validation by qRT-PCR. Analysis of target genes/pathways was characterized in silico. 06 RSA patients were infected with C. trachomatis, while chlamydial load was found to be 6000-12,000 copies/ml. 110 circulating miRNAs were expressed differentially in infected RSA patients compared with controls. Of these, 16 were overexpressed and 94 downregulated. 06 differentially expressed circulating miRNAs were selected to validate the microarray results. qRT-PCR data confirmed the reliability of the microarray results: miR-4443, -5100, -7975 showed statistically significant upregulation, while miR-6808-5p, -3148, -6727-5p were significantly downregulated in infected RSA patients versus controls. Chlamydial load was positively correlated with these upregulated miRNAs. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that target genes of miRNAs in RSA are involved in AMPK, Akt and mTOR signaling pathways. Overall results indicate that differentially expressed circulating miRNAs are involved in pathogenesis of C. trachomatis-associated RSA and have the potential to be used as biomarkers for predicting RSA.

Circulating microRNAs as diagnostic biomarkers for ischemic stroke: evidence from comprehensive analysis and real-world validation.

Ischemic stroke (IS) is the majority of strokes which remain the second leading cause of deaths in the last two decades. Circulating microRNAs (miRNAs) have been suggested as potential diagnostic and therapeutic tools for IS by previous studies analyzing their differential expression. However, inconclusive and controversial conclusions of these results have to be addressed. In this study, comprehensive analysis and real-world validation were performed to assess the associations between circulating miRNAs and IS. 29 studies with 112 miRNAs were extracted after manual selection and filtering, 12 differentially expressed miRNAs were obtained from our results of meta-analysis. These miRNAs were evaluated in 20 IS patients, compared to 20 healthy subjects. 4 miRNAs (hsa-let-7e-5p, hsa-miR-124-3p, hsa-miR-17-5p, hsa-miR-185-5p) exhibited the significant expression level in IS patient plasma samples. Pathway and biological process enrichment analysis for the target genes of the 4 validated miRNAs identified cellular senescence and neuroinflammation as key post-IS response pathways. The results of our analyses closely correlated with the pathogenesis and implicated pathways observed in IS subjects suggested by the literature, which may provide aid in the development of circulating diagnostic or therapeutic targets for IS patients.

Correlation between Circulating miR-16, miR-29a, miR-144 and miR-150, and the Radiotherapy Response and Survival of Non-Small-Cell Lung Cancer Patients.

Despite the success of current therapy concepts, patients with advanced non-small-cell lung cancer (NSCLC) still have a very poor prognosis. Therefore, biological markers are urgently needed, which allow the assessment of prognosis, or prediction of the success of therapy or resistance in this disease. Circulating microRNAs (miRs) have potential as biomarkers for the prognosis and prediction of response to therapy in cancer patients. Based on recent evidence that circulating miR-16, miR-29a, miR-144 and miR-150 can be regulated by ionizing radiation, the concentration of these four miRs was assessed in the plasma of NSCLC patients at different time points of radiotherapy by digital droplet PCR (ddPCR). Furthermore, their impact on patients' prognosis was evaluated. The mean plasma levels of miR-16, miR-29a, miR-144 and miR-150 significantly differed intra- and inter-individually, and during therapy in NSCLC patients, but showed a strong positive correlation. The individual plasma levels of miR-16, miR-29a and miR-144 had prognostic value in NSCLC patients during or at the end of radiotherapy in Cox's regression models. NSCLC patients with low levels of these three miRs at the end of radiotherapy had the worst prognosis. However, miR-150 plasma levels and treatment-dependent changes were not predictive. In conclusion, circulating miR-16, miR-29a and miR-144, but not miR-150, have a prognostic value in NSCLC patients undergoing radiotherapy.

Modulation of miR-146b Expression during Aging and the Impact of Physical Activity on Its Expression and Chondrogenic Progenitors.

The finding of molecules associated with aging is important for the prevention of chronic degenerative diseases and for longevity strategies. MicroRNAs (miRNAs) are post-transcriptional regulators involved in many biological processes and miR-146b-5p has been shown to be involved in different degenerative diseases. However, miR-146b-5p modulation has not been evaluated in mesenchymal stem cells (MSCs) commitment or during aging. Therefore, the modulation of miR-146b-5p in the commitment and differentiation of mesenchymal cells as well as during maturation and aging in zebrafish model were analyzed. In addition, circulating miR-146b-5p was evaluated in human subjects at different age ranges. Thus, the role of physical activity in the modulation of miR-146b-5p was also investigated. To achieve these aims, RT (real-time)-PCR, Western blot, cell transfections, and three-dimensional (3D) culture techniques were applied. Our findings show that miR-146b-5p expression drives MSCs to adipogenic differentiation and increases during zebrafish maturation and aging. In addition, miR-146b-5p expression is higher in females compared to males and it is associated with the aging in humans. Interestingly, we also observed that the physical activity of walking downregulates circulating miR-146b-5p levels in human females and increases the number of chondroprogenitors. In conclusion, miR-146b-5p can be considered an age-related marker and can represent a useful marker for identifying strategies, such as physical activity, aimed at counteracting the degenerative processes of aging.

Eight weeks of combined exercise training do not alter circulating microRNAs-29a, -133a, -133b, and -155 in young, healthy men.

PURPOSE: Individuals with a family history of type 2 diabetes (FH +) have an increased risk of developing type 2 diabetes. Circulating microRNAs (miRNAs) have been implicated as biomarkers of type 2 diabetes risk. Here, we investigated if four circulating miRNAs related to glucose metabolism were altered in men with a FH + and we conducted a preliminary analysis to determine if miRNA expressions were responsive to 8 weeks of combined exercise training. METHODS: Sixteen young healthy men (mean ± SD; age 22.5 ± 2.5; BMI 26.4 ± 4.0) with FH + or without a family history of type 2 diabetes (FH -) underweight 8 weeks of combined endurance and resistance exercise training (n = 8 FH -; n = 8 FH +). The expression of miR-29a, miR-133a, miR-133b, and miR-155 were measured in serum before and after exercise training. QIAGEN's Ingenuity® Pathway Analysis was used to examine miRNA target genes and their involvement in glucose metabolism signaling pathways. RESULTS: There were no differences in miRNA expressions between FH - and FH + . Exercise training did not alter miRNA expressions in either FH - or FH + despite improvements in insulin sensitivity, aerobic capacity, and muscular strength. miR-29a and miR-155 were inversely related to fasting glucose, and miR-133a and miR-133b were negatively correlated with glucose tolerance; however, correlations were not observed with insulin sensitivity. CONCLUSIONS: The circulating miRNAs- miR-29a, miR-133a, miR-133b, and miR-155 are related to measures of glucose metabolism in healthy, normoglycemic men, but do not reflect peripheral insulin sensitivity or improvements in metabolic health following 8 weeks of combined exercise training.

HDL and microRNAs.

In previous chapters, we know that high-density lipoproteins (HDLs) could act at multiple cell lines and then trigger intracellular molecular pathway to prevent several metabolic diseases. Besides the classic genes regulating cholesterol efflux and reverse cholesterol transport (RCT), microRNAs (miRNAs) could also affect HDLs biogenesis, metabolism, and functions. This chapter summarizes the miRNAs, which regulate HDLs functions in table. In addition, HDLs are good vectors for miRNAs. They could carry miRNAs in circulation and take them into several cells such as macrophages and endothelial cells. Complete understanding of the miRNAs associated with HDL regulation would give us broader insights to prevent and treat metabolic diseases.

Circulating miR-200 family as predictive markers during systemic therapy of metastatic breast cancer.

PURPOSE: Circulating miRNAs can provide valid prognostic and predictive information for breast cancer diagnosis and subsequent management. They may comprise quintessential biomarkers that can be obtained minimally invasively from liquid biopsy in metastatic breast cancer patients. Therefore, they would be clinically crucial for monitoring therapy response, with the goal of detecting early relapse. This study investigated miRNA expression in patients with early and/or late relapse, and the predictive value for assessing overall (OS) and progression-free survival (PFS). METHODS: Forty-seven patients with metastatic breast cancer from the University Women's Hospital Heidelberg were enrolled in this study. Expression of miR-200a, miR-200b, miR-200c, miR-141, and miR-429 was analyzed by RT-qPCR before a new line of systemic therapy and after the first cycle of a respective therapy. Tumor response was assessed every 3 months using the RECIST criteria. Statistical analysis focused on the relation of miR-200s expression and early vs. late cancer relapse in relation to systemic treatment. The association of miRNAs with PFS and OS was investigated. RESULTS: Before starting a new line of systemic therapy, miR-429 (p = 0.024) expression was significantly higher in patients with early relapse (PFS ≤ 4 months) than in patients with late relapse (PFS > 4 months). After one cycle of systemic therapy, miR-200a (p = 0.039), miR-200b (p = 0.003), miR-141 (p = 0.017), and miR-429 (p = 0.010) expression was higher in early than in late progressive cancer. In addition, 4 out of 5 miR-200 family members (miR-200a, miR-200b, miR-141, and miR-429) predicted PFS (p = 0.048, p = 0.008, p = 0.026, and p = 0.016, respectively). Patients with heightened miRNA levels showed a significant reduction in OS and PFS. CONCLUSION: Circulating miR-200s were differentially expressed among patients with late and/or early relapse. 4 of 5 members of the miR-200 family predicted significantly early relapse after systemic treatment. Our results encourage the use of circulating miR-200s as valuable prognostic biomarkers during metastatic breast cancer therapy.

Hepato-Protective Effects of Delta-Tocotrienol and Alpha-Tocopherol in Patients with Non-Alcoholic Fatty Liver Disease: Regulation of Circulating MicroRNA Expression.

MicroRNAs (miRNAs) play a key role in the regulation of genes for normal metabolism in the liver. Dysregulation of miRNAs is involved in the development and progression of non-alcoholic fatty liver disease (NAFLD). We aimed to explore changes in circulating miRNA expression in response to delta-tocotrienol (δT3) and alpha-tocopherol (αTF) supplementation and correlate them with relevant biochemical markers in patients with NAFLD. In total, 100 patients with NAFLD were randomized to either receive δT3 (n = 50) 300 mg or αTF (n = 50) 268 mg twice/day for 48 weeks. Plasma expression of miRNA-122, -21, -103a-2, -421, -375 and -34a were determined at baseline, 24 and 48 weeks of intervention using RT-qPCR. Both δT3 and αTF significantly downregulated expression of miRNA-122, -21, -103a-2, -421, -375 and -34a. Moreover, δT3 was more effective than αTF in reducing expression of miRNA-375 and -34a. A significant correlation was observed between miRNA expression and biochemical markers of hepatic steatosis, insulin resistance (IR), oxidative stress (OS), inflammation and apoptosis. δT3 and αTF exert hepato-protective effects by downregulating miRNAs involved in hepatic steatosis, IR, OS, inflammation and apoptosis in patients with NAFLD. Furthermore, δT3 has more pronounced effects than αTF in reducing miR-375 and miR-34a, which are linked to regulation of inflammation and apoptosis.

A microRNA Signature for the Diagnosis of Statins Intolerance.

Atherosclerotic cardiovascular diseases (ASCVD) are the leading cause of morbidity and mortality in Western societies. Statins are the first-choice therapy for dislipidemias and are considered the cornerstone of ASCVD. Statin-associated muscle symptoms are the main reason for dropout of this treatment. There is an urgent need to identify new biomarkers with discriminative precision for diagnosing intolerance to statins (SI) in patients. MicroRNAs (miRNAs) have emerged as evolutionarily conserved molecules that serve as reliable biomarkers and regulators of multiple cellular events in cardiovascular diseases. In the current study, we evaluated plasma miRNAs as potential biomarkers to discriminate between the SI vs. non-statin intolerant (NSI) population. It is a multicenter, prospective, case-control study. A total of 179 differentially expressed circulating miRNAs were screened in two cardiovascular risk patient cohorts (high and very high risk): (i) NSI (n = 10); (ii) SI (n = 10). Ten miRNAs were identified as being overexpressed in plasma and validated in the plasma of NSI (n = 45) and SI (n = 39). Let-7c-5p, let-7d-5p, let-7f-5p, miR-376a-3p and miR-376c-3p were overexpressed in the plasma of SI patients. The receiver operating characteristic curve analysis supported the discriminative potential of the diagnosis. We propose a three-miRNA predictive fingerprint (let-7f, miR-376a-3p and miR-376c-3p) and several clinical variables (non-HDLc and years of dyslipidemia) for SI discrimination; this model achieves sensitivity, specificity and area under the receiver operating characteristic curve (AUC) of 83.67%, 88.57 and 89.10, respectively. In clinical practice, this set of miRNAs combined with clinical variables may discriminate between SI vs. NSI subjects. This multiparametric model may arise as a potential diagnostic biomarker with clinical value.

Circulating microRNAs in Medicine.

Circulating microRNAs (c-microRNAs, c-miRNAs), which are present in almost all biological fluids, are promising sensitive biomarkers for various diseases (oncological and cardiovascular diseases, neurodegenerative pathologies, etc.), and their signatures accurately reflect the state of the body. Studies of the expression of microRNA markers show that they can enable a wide range of diseases to be diagnosed before clinical symptoms are manifested, and they can help to assess a patient's response to therapy in order to correct and personalize treatments. This review discusses the latest trends in the uses of miRNAs for diagnosing and treating various diseases, viral and non-viral. It is concluded that exogenous microRNAs can be used as high-precision therapeutic agents for these purposes.

Expression of Selected Genes and Circulating microRNAs in Patients with Celiac Disease.

Background and Objectives: Celiac disease (CD) is an immune-mediated enteropathy with characteristic intestinal alterations. CD occurs as a chronic inflammation secondary to gluten sensitivity in genetically susceptible individuals. Until now, the exact cause of the disease has not been established, which is why new studies have appeared that address the involvement of various genes and microRNAs (miRNAs) in the pathogenesis. The aim of the study is to describe the expression of selected genes (Wnt family member 3, WNT3; Wnt family member 11, WNT11; tumor necrosis factor alpha, TNFα; mitogen-activated protein kinase 1, MAPK1; AKT serine/threonine kinase 3, AKT3; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha, PIK3CA; and cyclin D1, CCND1) and miRNAs (miR-192-5p, miR-194-5p, miR-449a and miR-638) in adult patients with CD. Materials and Methods: In total, 15 patients with CD at diagnosis (newly diagnosed), 33 patients on a gluten-free diet (GFD) for at least 1 year and 10 controls (control) were prospectively included. Blood samples were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Results: The results show that TNFα, MAPK1 and CCND1 were significantly overexpressed (p = 0.0249, p = 0.0019 and p = 0.0275, respectively) when comparing the newly diagnosed group to the controls. The other genes studied in CD patients were mostly with high values compared to controls, without reaching statistical significance. Among the miRNAs, the closest to a statistically significant value was miR-194-5p when the newly diagnosed group versus control (p = 0.0510) and GFD group versus control (p = 0.0671) were compared. The DIANA and miRNet databases identified significant functional activity for miR-449a and miR-192-5p and an interconnection of miR-194-5p and miR-449a with CCND1. Conclusions: In conclusion, genes and circulating miRNAs require further studies as they could represent important biomarkers in clinical practice.

MiR-22, a serum predictor of poor outcome and therapy response in diffuse large B-cell lymphoma patients.

Diffuse large B-cell lymphoma (DLBCL) is an aggressive, heterogeneous neoplasm where prognostication and therapeutic decision are challenging. The available prognostic tools are not able to identify all patients refractory to treatment. MicroRNAs, small RNAs frequently deregulated in cancer, stably circulate in biofluids, representing interesting candidates for non-invasive biomarkers. Here we validated serum miR-22, an evolutionarily conserved microRNA, as a prognostic/predictive biomarker in DLBCL. Moreover, we found that its expression and release from DLBCL cells are related to therapy response and adversely affect cell proliferation. These results suggest that miR-22 is a promising complementary or even independent non-invasive biomarker for DLBCL management.

Circulating miR-455-3p, miR-5787, and miR-548a-3p as potential noninvasive biomarkers in the diagnosis of acute graft-versus-host disease: a validation study.

Currently, acute graft-versus-host disease (aGVHD) diagnosis is based on clinical features and pathological findings. Until now, there is no non-invasive diagnostic test for aGVHD. MicroRNAs may act as promising predictive, diagnostic, or prognostic biomarkers for aGVHD. The purpose of the current study was to validate circulating microRNAs as diagnostic biomarkers to assist clinicians in promptly diagnosing aGVHD, so that treatment can be initiated earlier. In the present study, we evaluated six microRNAs (miR-455-3p, miR-5787, miR-6729-5p, miR-6776-5p, miR-548a-3p, and miR-6732-5p) selected from miRNA array data in 40 aGVHD patients compared to 40 non-GVHD patients with RT-qPCR. Target genes of differentially expressed microRNAs (DEMs) were predicted using Targetscan, miRanda, miRDB, miRWalk, PICTAR5, miRmap, DIANA, and miRTarBase algorithms, and their functions were analyzed using EnrichNet, Metascape, and DIANA-miRPath databases. The expressions of plasma miR-455-3p and miR-5787 were significantly downregulated, whereas miR-548a-3p was significantly upregulated in aGVHD patients compared to non-GVHD patients. Moreover, DEMs showed potentially high diagnostic accuracy for aGVHD. In silico analysis of DEMs provided valuable information on the role of DEMs in GVHD, immune regulation, and inflammatory response. Our study suggested that miR-455-3p, miR-5787, and miR-548a-3p could be used as potential noninvasive biomarkers in the diagnosis of aGVHD in addition to possible therapeutic targets in aGVHD.

Evaluation of circulating microRNAs-211 and 25 as diagnostic biomarkers of colorectal cancer.

Colorectal cancer is one of the most prevalent and deadly cancers worldwide. MicroRNAs are short single stranded non-coding RNAs that play important roles in carcinogenesis, tumor growth and tumor survival. Circulating microRNAs are increasingly becoming efficient and important biomarkers for several types of cancers. Herein, we aim to evaluate the diagnostic potentials of plasma microRNA-211 and microRNA-25 in colorectal cancer patients. Forty-four patients diagnosed with colorectal cancer and 40 healthy controls were recruited for the present study. Expressions of circulating microRNAs -211 and 25 were assessed by quantitative real-time polymerase chain reaction (RT-qPCR). Expression of transforming growth factor-beta, a key factor in tumorigenesis and a key inducer of epithelial to mesenchymal transition was assessed by enzyme-linked immunosorbent assay (ELISA) in patients' tissue and plasma. Our results demonstrated upregulated expressions of plasma microRNAs-211 and 25 correlated with the high transforming growth factor-beta (TGF-ß1) expression in patients. In addition, plasma levels were positively correlated with lymph node metastasis. Moreover, receiver operating characteristic analysis demonstrated the reliability of microRNAs-211 and 25 for discriminating colorectal cancer patients from healthy individuals. MicroRNA-211 and microRNA-25 might have a tumorigenic role in colorectal cancer and their plasma levels could be potential biomarkers in its diagnosis.

Identification of transcription factors and construction of a novel miRNA regulatory network in primary osteoarthritis by integrated analysis.

BACKGROUNDS: As osteoarthritis (OA) disease-modifying therapies are not available, novel therapeutic targets need to be discovered and prioritized. Here, we aim to identify miRNA signatures in patients to fully elucidate regulatory mechanism of OA pathogenesis and advance in basic understanding of the genetic etiology of OA. METHODS: Six participants (3 OA and 3 controls) were recruited and serum samples were assayed through RNA sequencing (RNA-seq). And, RNA-seq dataset was analysed to identify genes, pathways and regulatory networks dysregulated in OA. The overlapped differentially expressed microRNAs (DEMs) were further screened in combination with the microarray dataset GSE143514. The expression levels of candidate miRNAs were further validated by quantitative real-time PCR (qRT-PCR) based on the GEO dataset (GSE114007). RESULTS: Serum samples were sequenced interrogating 382 miRNAs. After screening of independent samples and GEO database, the two comparison datasets shared 19 overlapped candidate micRNAs. Of these, 9 up-regulated DEMs and 10 down-regulated DEMs were detected, respectively. There were 236 target genes for up-regulated DEMs and 400 target genes for those down-regulated DEMs. For up-regulated DEMs, the top 10 hub genes were KRAS, NRAS, CDC42, GDNF, SOS1, PIK3R3, GSK3B, IRS2, GNG12, and PRKCA; for down-regulated DEMs, the top 10 hub genes were NR3C1, PPARGC1A, SUMO1, MEF2C, FOXO3, PPP1CB, MAP2K1, RARA, RHOC, CDC23, and CREB3L2. Mir-584-5p-KRAS, mir-183-5p-NRAS, mir-4435-PIK3R3, and mir-4435-SOS1 were identified as four potential regulatory pathways by integrated analysis. CONCLUSIONS: We have integrated differential expression data to reveal putative genes and detected four potential miRNA-target gene pathways through bioinformatics analysis that represent new mediators of abnormal gene expression and promising therapeutic targets in OA.

Circulating microRNA-92a-3p in colorectal cancer: a review.

Recent studies have found that microRNAs (miRNAs) are present in body fluids, including blood, cerebrospinal fluid, tears, saliva, breast milk, and urine in a stable form, and are called circulating miRNAs. Although their biological roles remain to be determined, circulating miRNAs are considered as mediators of intercellular communication like hormones and cytokines. Because circulating miRNAs can be collected in a non-invasive manner called as "liquid biopsy", they have also been studied as potential biomarkers for early detection, evaluation of therapeutic effects, and prediction of prognosis in various diseases, including cancers. In this review, we focus on the studies on circulating microRNA-92a-3p (miR-92a-3p) in colorectal cancer (CRC), considering their existence form, isolation methods, potential as biomarkers, and roles in CRC development and progression.