Shared genes of polycystic ovary syndrome and sedentary behavior as a novel immune landscape biomarker for endometrial cancer.

Endometrial cancer (EC) is associated with significant risk factors such as polycystic ovarian syndrome (PCOS) and sedentary behavior. In our study, we aim to employ machine learning algorithms to investigate the potential molecular processes that underlie their interaction and explore their respective roles in the diagnosis and immunotherapy of EC. The GEO database provides access to microarray data, which was utilized in this study to identify gene expression modules associated with PCOS and sedentary behavior, using weighted gene expression network analysis (WGCNA). Cluego software was then employed to investigate the energy enrichment of shared pathways in both PCOS and sedentary individuals, and differential gene analysis was used to confirm another two databases. The miRNAs-mRNAs controlled network was constructed to verify the pathway. The immune-related factors of the shared pathway in EC were then analyzed. Finally, to validate our findings, we conducted cell experiments using EC cell lines (AN3CA, KLE, Ishikawa, RL95-2, and HEC-1A). We found that increased intracellular aromatic compound anabolism is a common feature of both PCOS and sedentary individuals. We then developed a disease pathway model that was based on the common genetic characteristics of PCOS and sedentary behavior. We utilized pathway typing in EC samples and found a significant survival difference between the two subgroups, with the upregulated expression type exhibiting an immune-hot phenotype. Finally, the experimental results confirmed the expression of the hub gene (NAA15) in EC. The findings of our study suggest that genes related to the intracellular aromatic compound metabolic pathway can be used for immunotherapy of EC.

Circulating adipose-tissue miRNAs in gastrointestinal cancer patients and their association with the level and type of adiposity at body composition analysis.

Background: Adipose tissue (AT) wasting in cancer is an early catabolic event with negative impact on outcomes. Circulating miRNAs may promote body weight loss and cachexia. We measured circulating miRNAs linked to AT alterations and compared their levels between i) gastrointestinal (GI) cancer patients and controls, ii) cachectic and non-cachectic cancer patients, and iii) according to adiposity level and its distribution. Methods: Patients with GI cancer and subjects with benign diseases as controls were considered. Cachexia was assessed and adiposity evaluated by CT-scan for subcutaneous AT area (SAT), visceral AT area and the total AT area (TAT). MiRNAs involved were measured in plasma by RT-qPCR. Results: 37 naïve GI cancer patients and 14 controls were enrolled. Patients with cachexia presented with lower SAT compared to non-cachectic (p < 0.05). In cancer patients, we found higher levels of miR-26a, miR-128, miR-155 and miR-181a vs. controls (p < 0.05). Cancer patients with BMI < 25 kg/m2 showed higher levels of miR-26a vs. those with BMI ≥ 25 (p = 0.035). MiR-26a and miR-181a were higher in cachectic and non-cachectic vs. controls (p < 0.05). Differences between cachectic and controls were confirmed for miR-155 (p < 0.001) but not between non-cachectic vs. control (p = 0.072). MiR-155 was higher in cachectic patients with low TAT vs. those without cachexia and high TAT (p = 0.036). Conclusion: Our data confirm a modulation of specific and different miRNAs involved in AT metabolism in cancer and cachexia. MiR-155 levels were higher in patients presenting with cachexia and low adiposity with implications in the pathogenic mechanisms and clinical consequences of GI cancer patients.

The Host miR-17-92 Cluster Negatively Regulates Mouse Mammary Tumor Virus (MMTV) Replication Primarily Via Cluster Member miR-92a.

The mouse mammary tumor virus (MMTV) is a well-known causative agent of breast cancer in mice. Previously, we have shown that MMTV dysregulates expression of the host miR-17-92 cluster in MMTV-infected mammary glands and MMTV-induced tumors. This cluster, better known as oncomiR-1, is frequently dysregulated in cancers, particularly breast cancer. In this study, our aim was to uncover a functional interaction between MMTV and the cluster. Our results reveal that MMTV expression led to dysregulation of the cluster in both mammary epithelial HC11 and HEK293T cells with the expression of miR-92a cluster member being affected the most. Conversely, overexpression of the whole or partial cluster significantly repressed MMTV expression. Notably, overexpression of cluster member miR-92a alone repressed MMTV expression to the same extent as overexpression of the complete/partial cluster. Inhibition of miR-92a led to nearly a complete restoration of MMTV expression, while deletion/substitution of the miR-92a seed sequence rescued MMTV expression. Dual luciferase assays identified MMTV genomic RNA as the potential target of miR-92a. These results show that the miR-17-92 cluster acts as part of the cell's well-known miRNA-based anti-viral response to thwart incoming MMTV infection. Thus, this study provides the first evidence highlighting the biological significance of host miRNAs in regulating MMTV replication and potentially influencing tumorigenesis.

Small molecules targeting microRNAs: new opportunities and challenges in precision cancer therapy.

Noncoding RNAs, especially miRNAs, play a pivotal role in cancer initiation and metastasis, underscoring their susceptibility to precise modulation via small molecule inhibitors. This review examines the innovative strategy of targeting oncogenic miRNAs with small drug-like molecules, an approach that can reshape the cancer treatment landscape. We review the current understanding of the multifaceted roles of miRNAs in oncogenesis, highlighting emerging therapeutic paradigms that have the potential to expand cancer treatment options. As research on small molecule inhibitors of miRNA is still in its early stages, ongoing investigative efforts and the development of new technologies and chemical matter are essential to fulfill the significant potential of this innovative approach to cancer treatment.

Pericardial Fluid Accumulates microRNAs That Regulate Heart Fibrosis after Myocardial Infarction.

Pericardial fluid (PF) has been suggested as a reservoir of molecular targets that can be modulated for efficient repair after myocardial infarction (MI). Here, we set out to address the content of this biofluid after MI, namely in terms of microRNAs (miRs) that are important modulators of the cardiac pathological response. PF was collected during coronary artery bypass grafting (CABG) from two MI cohorts, patients with non-ST-segment elevation MI (NSTEMI) and patients with ST-segment elevation MI (STEMI), and a control group composed of patients with stable angina and without previous history of MI. The PF miR content was analyzed by small RNA sequencing, and its biological effect was assessed on human cardiac fibroblasts. PF accumulates fibrotic and inflammatory molecules in STEMI patients, namely causing the soluble suppression of tumorigenicity 2 (ST-2), which inversely correlates with the left ventricle ejection fraction. Although the PF of the three patient groups induce similar levels of fibroblast-to-myofibroblast activation in vitro, RNA sequencing revealed that PF from STEMI patients is particularly enriched not only in pro-fibrotic miRs but also anti-fibrotic miRs. Among those, miR-22-3p was herein found to inhibit TGF-ß-induced human cardiac fibroblast activation in vitro. PF constitutes an attractive source for screening diagnostic/prognostic miRs and for unveiling novel therapeutic targets in cardiac fibrosis.

Dysregulation of plasma circulating microRNAs in all-cause and cause-specific cancers: the Rotterdam Study.

MicroRNAs (miRNAs) are small non-coding RNAs involved in post-transcriptional regulation of gene expression. Mounting evidence underscores the dysregulation of miRNAs to be associated with cancer development and progression by acting as tumour suppressors and oncogenes. However, their potential as biomarkers for early diagnosis of different cancers remains incompletely unraveled. We explored the relationship between plasma circulatory miRNAs and cancer risk within the population-based Rotterdam Study cohort. Plasma samples were collected at baseline (between 2002 and 2005) and miRNA levels were measured in 1,999 participants, including 169 prevalent cancer cases. The occurrence of cancer was assessed by continuous monitoring of medical records in 1,830 cancer-free participants until January 1, 2015. We assessed the association between incidence of five common cancers (blood, lung, breast, prostate, and colorectal) and 591 miRNAs well-expressed in plasma, using adjusted Cox proportional-hazards regression models. Our longitudinal analysis identified 13 miRNAs significantly associated with incident hematologic tumors surpassing the Bonferroni-corrected P < 8.46 × 10- 5, 12 of them (miR-6124, miR-6778-5p, miR-5196, miR-654-5p, miR-4478, miR-4430, miR-4534, miR-1915-3p, miR-4644, miR-4292, miR-7111-5p, and miR-6870-5p) were also associated with prevalent hematologic tumors in the cross-sectional analysis at the baseline. In-silico analyses of the putative target genes of 13 identified miRNAs highlighted relevant genes and pathways linked to hematologic tumors. While no significant miRNA association was found for other four studied cancers, two miRNAs (miR-3157-5p and miR-3912-5p) showed nominal association with incident of three different cancer types. Overall, this study indicates that plasma levels of several miRNAs are dysregulated in hematologic tumors, highlighting their potential as biomarkers for early diagnosis as well as being involved in the pathogenesis of blood cancers.

Identification of miRNA signature in cancer-associated fibroblast to predict recurrent prostate cancer.

BACKGROUND: Cancer-associated fibroblasts (CAFs) are one of the major components of prostate stromal cells, which play a crucial part in tumor development and treatment resistance. This study aimed to establish a model of CAFs-related microRNAs (miRNAs) to assess prognostic differences, tumor microenvironments, and screening of anticancer drugs by integrating data from single-cell RNA sequencing (scRNA-seq) and bulk RNA sequencing (buRNA-seq). METHODS: scRNA-seq and buRNA-seq data of primary prostate cancer (PCa) were downloaded from Gene Expression Omnibus and The Cancer Genome Atlas databases. Statistical methods including Least absolute shrinkage and selection operator (Lasso), Lasso penalized, Random Forest, Random Forest Combination, and Support Vector Machine (SVM) were performed to select hub miRNAs. Pathway analyses and assessment of infiltrating immune cells were conducted using Gene Set Enrichment Analysis and the CIBERSORT algorithm. The expression of CAFs-related miRNAs in fibroblast cell lines were validated through quantitative real-time PCR. Cell Counting Kit 8 (CCK8), wound-healing, clone formation, and cell migration assays were used to explore cell proliferation, growth, and migration in vitro. A mouse xenograft model was established to investigate the effect of CAFs on tumor growth in vivo. RESULTS: Through single-cell transcriptomics analysis in 34 PCa patients, 89 CAFs-related mRNAs were identified. A prognostic model based on 9 CAFs-related miRNAs (hsa-miR-1258, hsa-miR-133b, hsa-miR-222-3p, hsa-miR-145-3p, hsa-miR-493-5p, hsa-miR-96-5p, hsa-miR-15b-5p, hsa-miR-106b-5p, and hsa-miR-191-5p) was established to predict biochemical recurrence (BCR). We have determined through two prediction methods that NVP-TAE684 may be the optimal targeted therapy drug for treating CAFs. Downregulation of hsa-miR-106b-5p in CAFs significantly suppressed cell proliferation, migration, and colony formation in vitro. In vivo studies using a xenograft model further confirmed that hsa-miR-106b-5p downregulation significantly reduced tumor growth. CONCLUSION: Our findings conducted an integrated bioinformatic analysis to develop a CAFs-related miRNAs model that provides prognostic insights into individualized and precise treatment for prostate adenocarcinoma patients. Downregulation of miR-106b-5p in CAFs significantly suppressed tumor growth, suggesting a potential therapeutic target for cancer treatment.

Deciphering the Molecular Complexity of Hepatocellular Carcinoma: Unveiling Novel Biomarkers and Therapeutic Targets Through Advanced Bioinformatics Analysis.

BACKGROUND: Hepatocellular carcinoma (HCC) represents a primary liver tumor characterized by a bleak prognosis and elevated mortality rates, yet its precise molecular mechanisms have not been fully elucidated. This study uses advanced bioinformatics techniques to discern differentially expressed genes (DEGs) implicated in the pathogenesis of HCC. The primary objective is to discover novel biomarkers and potential therapeutic targets that can contribute to the advancement of HCC research. METHODS: The bioinformatics analysis in this study primarily utilized the Gene Expression Omnibus (GEO) database as data source. Initially, the Transcriptome analysis console (TAC) screened for DEGs. Subsequently, we constructed a protein-protein interaction (PPI) network of the proteins associated to the identified DEGs with the STRING database. We obtained our hub genes using Cytoscape and confirmed the results through the GEPIA database. Furthermore, we assessed the prognostic significance of the identified hub genes using the GEPIA database. To explore the regulatory interactions, a miRNA-gene interaction network was also constructed, incorporating information from the miRDB database. For predicting the impact of gene overexpression on drug effects, we utilized CANCER DP. RESULTS: A comprehensive analysis of HCC gene expression profiles revealed a total of 4716 DEGs, consisting of 2430 upregulated genes and 2313 downregulated genes in HCC sample compared to healthy control group. These DEGs exhibited significant enrichment in key pathways such as the PI3K-Akt signaling pathway, nuclear receptors meta-pathway, and various metabolism-related pathways. Further exploration of the PPI network unveiled the P53 signaling pathway and pyrimidine metabolism as the most prominent pathways. We identified 10 hub genes (ASPM, RRM2, CCNB1, KIF14, MKI67, SHCBP1, CENPF, ANLN, HMMR, and EZH2) that exhibited significant upregulation in HCC samples compared to healthy control group. Survival analysis indicated that elevated expression levels of these genes were strongly associated with changes in overall survival in HCC patients. Lastly, we identified specific miRNAs that were found to influence the expression of these genes, providing valuable insights into potential regulatory mechanisms underlying HCC progression. CONCLUSION: The findings of this study have successfully identified pivotal genes and pathways implicated in the pathogenesis of HCC. These novel discoveries have the potential to significantly enhance our understanding of HCC at the molecular level, opening new ways for the development of targeted therapies and improved prognosis evaluation.

miRNA-Driven Regulation of Endothelial-to-Mesenchymal Transition Differs among Thoracic Aortic Aneurysms.

Thoracic aortic aneurysms (TAAs) represent a serious health concern, as they are associated with early aortic dissection and rupture. TAA formation is triggered by genetic conditions, in particular Marfan syndrome (MFS) and bicuspid aortic valve (BAV). During the aneurysmatic process, aortic endothelial cells can undergo endothelial-to-mesenchymal transition (End-MT) with consequent phenotypic and functional alterations. We previously documented that MFS TAA is characterized by miR-632-driven End-MT exacerbation, whereas in BAV aortopathy, the occurrence of this process remains still controversial. We investigated the End-MT process and the underlined regulatory mechanisms in BAV, TAV and MFS TAA tissues. Gene expression and immunohistochemical analysis were performed in order to analyze some important miRNAs and genes characterizing End-MT. We documented that BAV endothelium maintains the expression of the endothelial homeostasis markers, such as ERG, CD31 and miR-126-5p, while it shows lower levels of miR-632 and mesenchymal markers compared with MFS. Interestingly, we also found higher levels of miR-632 in MFS patients' blood. Our findings definitively demonstrate that the End-MT process does not characterize BAV that, among the other TAAs, better maintains the endothelial features. In addition, our results suggest miR-632 as a promising diagnostic/prognostic factor in MFS aortopathy.

Precision-engineered PEGylated liposome for dual payload delivery: enhancing efficacy of Doxorubicin hydrochloride and miR-145 mimics in breast cancer cells.

Micro-145 down-regulation is frequently found in breast cancers, indicating its potential as a therapeutic target. The introduction of exogenous miR-145 directly to the tumor sites has been a hurdle due to limited delivery, low bioavailability, and hence lower therapeutic efficacy. Thus, this study aims to synthesize and characterize PEGylated liposome co-loaded with Dox-HCl and miR-145 mimics to investigate its in-vitro anti-proliferative activity against MDA-MB-231 cells. The formulations were developed using a composite central design to optimize nanoparticle size and encapsulation efficiency (EE%) of Dox-HCl and miR-145 mimics. The optimized formulation exhibited the highest desirability function (D = 0.814) and displayed excellent stability over 60 days at 4 °C, maintaining a stable nanoparticle size and zeta potential, with relative EE% of Dox-HCl and miR-145 mimics on the final incubation day 94.97 ± 0.53% and 51.96 ± 2.67%, respectively. The system displayed a higher rate of drug release within 4 h of incubation at an acidic condition. Additionally, the optimized formulation demonstrated a higher toxicity (IC50 = 0.58 µM) against MDA-MB-231 cells than the free Dox- HCl and miR-145 regimen (IC50 = 1.00 µM). Our findings suggest that PEGylated liposome is tunable for effective concurrent delivery of anticancer drugs and therapeutic miRNAs into tumor cells, necessitating further investigation.

Non-coding RNAs in hepatocellular carcinoma metastasis: Remarkable indicators and potential oncogenic mechanism.

Non-coding RNAs (ncRNAs), as key regulators involving in intercellular biological processes, are more prominent in many malignancies, especially for hepatocellular carcinoma (HCC). Herein, we conduct a comprehensive review to summarize diverse ncRNAs roles in HCC metastatic mechanism. We focus on four signaling pathways that predominate in HCC metastatic process, including Wnt/ß-catenin, HIF-1α, IL-6, and TGF-ß pathways. MicroRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) employed different mechanisms to participate in the regulation of the key genes in these pathways, typical as interaction with DNA to control transcription, with RNA to control translation, and with protein to control stability. Therefore, ncRNAs may become potential biomarkers and therapeutic targets for HCC metastasis.

The interplay between microRNAs and Nrf2 signaling in human cancers.

MicroRNAs (miRNAs), as a class of nonprotein-coding RNAs, post-transcriptionally regulate the expression of target genes by base pairing to 3'-untranslated regions (3'-UTRs). Nuclear factor E2-related factor 2 (Nrf2) has been identified as a critical component of the antioxidant defense mechanism. Dysregulation is associated with chemoresistance and radioresistance in cancerous cells. MiRNA-mediated regulation of the Nrf2 signaling pathway has been shown to have important implications for the development of various cancers. In this article, we review the roles of miRNAs as regulators of the Nrf2 pathway in different human cancers. Ras-associated binding (Rab) proteins have an essential role regulation of vesicle transport, as well as oncogenic functions in preventing chemotherapy efficacy and cancer development. More importantly, increased evidence indicated that the interaction between miRNAs and Rabs has been determined to play critical roles in cancer therapy. However, the significant limitations in using miRNAs for therapeutic applications include cross-targeting and instability of miRNAs. The detailed aspect of the interaction of miRNAs and Rabs is not clearly understood. In the current review, we highlighted the involvement of these molecules as regulators of the Nrf2 pathway in cancer pathogenesis. Potential methods and several obstacles in developing miRNAs as an anticancer therapy are also mentioned.

Ultrasensitive Photoelectrochemical Biosensor for Dual-miRNAs Detection Based on Molecular Logic Gates and Methylene Blue Sensitized ZnO@CdS@Au Nanorods.

The occurrence of cancer is often closely related to multiple tumor markers, so it is important to develop multitarget detection methods. By the proper design of the input signals and logical operations of DNA logic gates, detection and diagnosis of cancer at different stages can be achieved. For example, in the early stages, specific input signals can be designed to correspond to early specific tumor markers, thereby achieving early cancer detection. In the late stage, logic gates for multitarget detection can be designed to simultaneously detect multiple biomarkers to improve diagnostic accuracy and comprehensiveness. In this work, we constructed a dual-target-triggered DNA logic gate for anchoring DNA tetrahedra, where methylene blue was embedded in the DNA tetrahedra to sensitize ZnO@CdS@Au, achieving ultrasensitive detection of the target substance. We tested the response of AND and OR logic gates to the platform. For AND logic gates, the sensing platform only responds when both miRNAs are present. In the concentration range of 10 aM to 10 nM, the photoelectric signal gradually increases with an increase of the target concentration. Subsequently, we used OR logic gates for miRNA detection. Even if only one target exists, the sensing platform exhibits excellent performance. Similarly, within the concentration range of 10 aM to 10 nM, the photoelectric signal gradually increases with an increase of the target concentration. The minimum detection limit is 1.10 aM. Whether it is the need to detect multiple targets simultaneously or only one of them, we can achieve it by selecting the appropriate logic gate. This strategy holds promising application prospects in fields such as biosensing, medical diagnosis, and environmental monitoring.

Deciphering the molecular landscape of ionising radiation-induced eye damage with the help of genomic data mining.

Even at low levels, exposure to ionising radiation can lead to eye damage. However, the underlying molecular mechanisms are not yet fully understood. We aimed to address this gap with a comprehensive in silico approach to the issue. For this purpose we relied on the Comparative Toxicogenomics Database (CTD), ToppGene Suite, Cytoscape, GeneMANIA, and Metascape to identify six key regulator genes associated with radiation-induced eye damage (ATM, CRYAB, SIRT1, TGFB1, TREX1, and YAP1), all of which have physical interactions. Some of the identified molecular functions revolve around DNA repair mechanisms, while others are involved in protein binding, enzymatic activities, metabolic processes, and post-translational protein modifications. The biological processes are mostly centred on response to DNA damage, the p53 signalling pathway in particular. We identified a significant role of several miRNAs, such as hsa-miR-183 and hsamiR-589, in the mechanisms behind ionising radiation-induced eye injuries. Our study offers a valuable method for gaining deeper insights into the adverse effects of radiation exposure.

Hodgkin lymphoma and liquid biopsy: a story to be told.

Hodgkin lymphoma (HL) represents a neoplasm primarily affecting adolescents and young adults, necessitating the development of precise diagnostic and monitoring tools. Specifically, classical Hodgkin lymphoma (cHL), comprising 90% of cases, necessitating tailored treatments to minimize late toxicities. Although positron emission tomography/computed tomography (PET/CT) has enhanced response assessment, its limitations underscore the urgency for more reliable progression predictive tools. Genomic characterisation of rare Hodgkin Reed-Sternberg (HRS) cells is challenging but essential. Recent studies employ single-cell molecular analyses, mass cytometry, and Next-Generation Sequencing (NGS) to unveil mutational landscapes. The integration of liquid biopsies, particularly circulating tumor DNA (ctDNA), extracellular vesicles (EVs), miRNAs and cytokines, emerge as groundbreaking approaches. Recent studies demonstrate ctDNA's potential in assessing therapy responses and predicting relapses in HL. Despite cHL-specific ctDNA applications being relatively unexplored, studies emphasize its value in monitoring treatment outcomes. Overall, this review underscores the imperative role of liquid biopsies in advancing HL diagnosis and monitoring.

The Effect of Physical Activity/Exercise on miRNA Expression and Function in Non-Communicable Diseases-A Systematic Review.

Exercise may differently affect the expression of key molecular markers, including skeletal muscle and circulating miRNAs, involved in cellular and metabolic pathways' regulation in healthy individuals and in patients suffering from non-communicable diseases (NCDs). Epigenetic factors are emerging as potential therapeutic biomarkers in the prognosis and treatment of NCDs and important epigenetic factors, miRNAs, play a crucial role in cellular pathways. This systematic review aims to underline the potential link between changes in miRNA expression after different types of physical activity/exercise in some populations affected by NCDs. In June 2023, we systematically investigated the following databases: PubMed, MEDLINE, Scopus, and Web of Science, on the basis of our previously established research questions and following the PRISMA guidelines. The risk of bias and quality assessment were, respectively, covered by ROB2 and the Newcastle Ottawa scale. Of the 1047 records extracted from the initial search, only 29 studies were found to be eligible. In these studies, the authors discuss the association between exercise-modulated miRNAs and NCDs. The NCDs included in the review are cancer, cardiovascular diseases (CVDs), chronic obstructive pulmonary disease (COPD), and type 2 diabetes mellitus (T2DM). We evidenced that miR-146, miR-181, miR-133, miR-21, and miRNA-1 are the most reported miRNAs that are modulated by exercise. Their expression is associated with an improvement in health markers and they may be a potential target in terms of the development of future therapeutic tools.

Molecular insights into programmed cell death in esophageal squamous cell carcinoma.

Background: Esophageal squamous cell carcinoma (ESCC) is a deadly type of esophageal cancer. Programmed cell death (PCD) is an important pathway of cellular self-extermination and is closely involved in cancer progression. A detailed study of its mechanism may contribute to ESCC treatment. Methods: We obtained expression profiling data of ESCC patients from public databases and genes related to 12 types of PCD from previous studies. Hub genes in ESCC were screened from PCD-related genes applying differential expression analysis, machine learning analysis, linear support vector machine (SVM), random forest and Least Absolute Shrinkage and Selection Operator (LASSO) regression analysis. In addition, based on the HTFtarget and TargetScan databases, transcription factors (TFs) and miRNAs interacting with the hub genes were selected. The relationship between hub genes and immune cells were analyzed using the CIBERSORT algorithm. Finally, to verify the potential impact of the screened hub genes on ESCC occurrence and development, a series of in vitro cell experiments were conducted. Results: We screened 149 PCD-related DEGs, of which five DEGs (INHBA, LRRK2, HSP90AA1, HSPB8, and EIF2AK2) were identified as the hub genes of ESCC. The area under the curve (AUC) of receiver operating characteristic (ROC) curve of the integrated model developed using the hub genes reached 0.997, showing a noticeably high diagnostic accuracy. The number of TFs and miRNAs regulating hub genes was 105 and 22, respectively. INHBA, HSP90AA1 and EIF2AK2 were overexpressed in cancer tissues and cells of ESCC. Notably, INHBA knockdown suppressed ECSS cell migration and invasion and altered the expression of important apoptotic and survival proteins. Conclusion: This study identified significant molecules with promising accuracy for the diagnosis of ESCC, which may provide a new perspective and experimental basis for ESCC research.

MicroRNA-mediated metabolic regulation of immune cells in cancer: an updated review.

The study of immunometabolism, which examines how immune cells regulate their metabolism to maintain optimal performance, has become an important area of focus in cancer immunology. Recent advancements in this field have highlighted the intricate connection between metabolism and immune cell function, emphasizing the need for further research. MicroRNAs (miRNAs) have gained attention for their ability to post-transcriptionally regulate gene expression and impact various biological processes, including immune function and cancer progression. While the role of miRNAs in immunometabolism is still being explored, recent studies have demonstrated their significant influence on the metabolic activity of immune cells, such as macrophages, T cells, B cells, and dendritic cells, particularly in cancer contexts. Disrupted immune cell metabolism is a hallmark of cancer progression, and miRNAs have been linked to this process. Understanding the precise impact of miRNAs on immune cell metabolism in cancer is essential for the development of immunotherapeutic approaches. Targeting miRNAs may hold potential for creating groundbreaking cancer immunotherapies to reshape the tumor environment and improve treatment outcomes. In summary, the recognition of miRNAs as key regulators of immune cell metabolism across various cancers offers promising potential for refining cancer immunotherapies. Further investigation into how miRNAs affect immune cell metabolism could identify novel therapeutic targets and lead to the development of innovative cancer immunotherapies.

Unveiling the Cutting-Edge Impact of Polarized Macrophage-Derived Extracellular Vesicles and MiRNA Signatures on TGF-ß Regulation within Lung Fibroblasts.

Depending on local cues, macrophages can polarize into classically activated (M1) or alternatively activated (M2) phenotypes. This study investigates the impact of polarized macrophage-derived Extracellular Vesicles (EVs) (M1 and M2) and their cargo of miRNA-19a-3p and miRNA-425-5p on TGF-ß production in lung fibroblasts. EVs were isolated from supernatants of M0, M1, and M2 macrophages and quantified using nanoscale flow cytometry prior to fibroblast stimulation. The concentration of TGF-ß in fibroblast supernatants was measured using ELISA assays. The expression levels of miRNA-19a-3p and miRNA-425-5p were assessed via TaqMan-qPCR. TGF-ß production after stimulation with M0-derived EVs and with M1-derived EVs increased significantly compared to untreated fibroblasts. miRNA-425-5p, but not miRNA-19a-3p, was significantly upregulated in M2-derived EVs compared to M0- and M1-derived EVs. This study demonstrates that EVs derived from both M0 and M1 polarized macrophages induce the production of TGF-ß in fibroblasts, with potential regulation by miRNA-425-5p.

Identification of miRNAs Present in Cell- and Plasma-Derived Extracellular Vesicles-Possible Biomarkers of Colorectal Cancer.

Globally, an increasing prevalence of colorectal cancer (CRC) prompts a need for the development of new methods for early tumor detection. MicroRNAs (also referred to as miRNAs) are short non-coding RNA molecules that play a pivotal role in the regulation of gene expression. MiRNAs are effectively transferred to extracellular vesicle (EVs) membrane sacs commonly released by cells. Our study aimed to examine the expression of miRNAs in four CRC cell lines and EVs derived from them (tumor EVs) in comparison to the normal colon epithelium cell line and its EVs. EVs were isolated by ultracentrifugation from the culture supernatant of SW480, SW620, SW1116, HCT116 and normal CCD841CoN cell lines and characterized according to the MISEV2023 guidelines. MiRNAs were analyzed by small RNA sequencing and validated by quantitative PCR. The performed analysis revealed 22 common miRNAs highly expressed in CRC cell lines and effectively transferred to tumor EVs, including miR-9-5p, miR-182-5p, miR-196b-5p, miR-200b-5p, miR-200c-3p, miR-425-5p and miR-429, which are associated with development, proliferation, invasion and migration of colorectal cancer cells, as well as in vesicle maturation and transport-associated pathways. In parallel, normal cells expressed miRNAs, such as miR-369 and miR-143, which play a role in proinflammatory response and tumor suppression. The analysis of selected miRNAs in plasma-derived EVs and tumor samples from CRC patients showed the similarity of miRNA expression profile between the patients' samples and CRC cell lines. Moreover, miR-182-5p, miR-196-5p, miR-425-5p and miR-429 were detected in several EV samples isolated from patients' plasma. Our results suggest that miR-182-5p, miR-196b-5p and miR-429 are differentially expressed between EVs from CRC patients and healthy donors, which might have clinical implications.