Endocrine therapy resistance (ETR) in breast cancer (BC) is a multicausal phenomenon with diverse alterations in the tumor cell interactome. Within these alterations, non-coding RNAs (ncRNAs) such as micro-RNAs (miRNAs) modulate the expression of tumor suppressor genes and proto-oncogenes, such as the ESR1 gene encoding estrogen receptor alpha (ERα). This work aims to review the effects of miRNAs targeting ERα mRNA and their mechanisms related to ETR in BC. A thorough review of the literature and an in silico study were carried out to elucidate the involvement of each miRNA, thus contributing to the understanding of ETR in BC.

MicroRNAs (miRNAs) are short non‑coding RNAs, which perform a key role in cellular differentiation and development. Most human diseases, particularly cancer, are linked to miRNA functional dysregulation implicated in the expression of tumor‑suppressive or oncogenic targets. Cancer hallmarks such as continued proliferative signaling, dodging growth suppressors, invasion and metastasis, triggering angiogenesis, and avoiding cell death have all been demonstrated to be affected by dysregulated miRNAs. Thus, for the treatment of different cancer types, the detection and quantification of this type of RNA is significant. The classical and current methods of RNA detection, including northern blotting, reverse transcription‑quantitative PCR, rolling circle amplification and next‑generation sequencing, may be effective but differ in efficiency and accuracy. Furthermore, these approaches are expensive, and require special instrumentation and expertise. Thus, researchers are constantly looking for more innovative approaches for miRNA detection, which can be advantageous in all aspects. In this regard, an RNA manipulation tool known as the CRISPR and CRISPR‑associated sequence 13 (CRISPR/Cas13) system has been found to be more advantageous in miRNA detection. The Cas13‑based miRNA detection approach is cost effective and requires no special instrumentation or expertise. However, more research and validation are required to confirm the growing body of CRISPR/Cas13‑based research that has identified miRNAs as possible cancer biomarkers for diagnosis and prognosis, and as targets for treatment. In the present review, current updates regarding miRNA biogenesis, structural and functional aspects, and miRNA dysregulation during cancer are described. In addition, novel approaches using the CRISPR/Cas13 system as a next‑generation tool for miRNA detection are discussed. Furthermore, challenges and prospects of CRISPR/Cas13‑based miRNA detection approaches are described.

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal malignant tumor characterized by a poor prognosis. A prominent feature of PDAC is the rich and dense stroma present in the tumor microenvironment (TME), which significantly hinders drug penetration. Cancer-associated fibroblasts (CAFs), activated fibroblasts originating from various cell sources, including pancreatic stellate cells (PSCs) and mesenchymal stem cells (MSCs), play a critical role in PDAC progression and TME formation. MicroRNAs (miRNAs) are small, single-stranded non-coding RNA molecules that are frequently involved in tumorigenesis and progression, exhibiting either oncolytic or oncogenic activity. Increasing evidence suggests that aberrant expression of miRNAs can mediate interactions between cancer cells and CAFs, thereby providing novel therapeutic targets for PDAC treatment. In this review, we will focus on the potential roles of miRNAs that target CAFs or CAFs-derived exosomes in PDAC progression, highlighting the feasibility of therapeutic strategies aimed at restoring aberrantly expressed miRNAs associated with CAFs, offering new pathways for the clinical management of PDAC.

Previous studies found that cigarette smoke (CS) exposure could induce NSCLC malignancy and miRNA dysregulation. Yet, the association of CS-induced miRNA dysregulation and NSCLC malignancy has not been clearly understood. This study aimed to evaluate the effect of CS exposure in smokers on the expression of miR-10b-5p and miR-320b in extracellular vesicles (EVs) from NSCLC patients.

Bioinformatic analysis was conducted to validate miRNA candidates. Blood and tissue samples were collected from NSCLC patients (n = 21) with smoking and non-smoking history. EVs were isolated from plasma and miRNAs were extracted from the isolated EVs. The miRNAs relative expression was analyzed and compared.

In silico analysis identified miR-320b and miR-10b-5p as potential biomarkers for diagnosing NSCLC in smokers. Experimental analysis revealed differential expression of EVs-associated miRNAs in NSCLC patients with smoking and non-smoking histories. EVs-associated miR-10b-5p was significantly overexpressed in smoker NSCLC patients (p = 0.000), while miR-320b expression was significantly lower in this group (p = 0.018). Additionally, smoking intensity influenced miRNA expression, with higher smoking intensity correlating with increased miR-10b-5p expression and decreased miR-320b expression. ROC analysis demonstrated that EVs were a superior source of miRNAs compared to plasma for NSCLC diagnostics. miR-10b-5p and miR-320b in EVs showed higher diagnostic performance (AUC 0.878; 0.739) compared to plasma (AUC 0.628; 0.559).

CS exposure induces different expression of miR-10b-5p and miR-320b in EVs of NSCLC patients with smoking history. EV-related miR-10b-5p and miR-320b showed potential to be utilized as prognostic biomarker for smokers NSCLC patients.

Melanoma is a devastating form of skin cancer characterized by a high mutational burden, limited treatment success, and dismal prognosis. Although immunotherapy and targeted therapies have significantly revolutionized melanoma treatment, the majority of patients fail to achieve durable responses, highlighting the urgent need for novel therapeutic strategies. Ferroptosis, an iron-dependent form of regulated cell death driven by the overwhelming accumulation of lipid peroxides, has emerged as a promising therapeutic approach in preclinical melanoma models. A deeper understanding of the ferroptosis landscape in melanoma based on its biology characteristics, including phenotypic plasticity, metabolic state, genomic alterations, and epigenetic changes, as well as the complex role and mechanisms of ferroptosis in immune cells could provide a foundation for developing effective treatments. In this review, we outline the molecular mechanisms of ferroptosis, decipher the role of melanoma biology in ferroptosis regulation, reveal the therapeutic potential of ferroptosis in melanoma, and discuss the pressing questions that should guide future investigations into ferroptosis in melanoma.

Synthetic gene circuits are logical circuits constructed by various biological elements based on engineering principles. However, the majority of current synthetic gene circuits are modulated through exogenous factors or endogenous inhibitory substances, which results in redundant structures and low efficiency, thereby greatly limiting their application scenarios. In this study, we developed a miCU sensor system comprising the Gal4-VP16 gene element, which enables real-time targeted monitoring of miR-9 and miR-124a during neural differentiation through transcriptional-translation two-step active regulation with a relatively low background signal. Additionally, the functional gene was replaced by P21 through the programmability of miCU, thereby achieving miRNA-mediated cell cycle arrest and suppression of cell migration in tumor cells. Furthermore, by strategically substituting the target miRNA with miR-155 and concurrently introducing the therapeutic gene Nrf2 into the miCU system, the integration of disease diagnosis and treatment in lipopolysaccharide (LPS)-induced acute liver injury (ALI) mouse models has been successfully achieved. Our study presented a programmable miRNA-responsive gene regulation platform, which may offer a robust tool for precise diagnosis and treatment in disease settings.

This review explores the current understanding and recent advancements in neuroblastoma, one of the most common extracranial solid pediatric cancers, accounting for ~ 15% of childhood cancer-related mortality. The hallmarks of NBL, including angiogenesis, metastasis, apoptosis resistance, cell cycle dysregulation, drug resistance, and responses to hypoxia and ROS, underscore its complex biology. The tumor microenvironment's significance in disease progression is acknowledged in this study, along with the pivotal role of cancer stem cells in sustaining tumor growth and heterogeneity. A number of molecular signatures are being studied in order to better understand the disease, with many of them serving as targets for the development of new therapeutics. This includes inhibitor therapies for NBL patients, which notably concentrate on ALK signaling, MDM2, PI3K/Akt/mTOR, Wnt, and RAS-MAPK pathways, along with regulators of epigenetic mechanisms. Additionally, this study offers an extensive understanding of the molecular therapies used, such as monoclonal antibodies and CAR-T therapy, focused on both preclinical and clinical studies. Radiation therapy's evolving role and the promise of stem cell transplantation-mediated interventions underscore the dynamic landscape of NBL treatment. This study has also emphasized the recent progress in the field of diagnosis, encompassing the adoption of artificial intelligence and liquid biopsy as a non-intrusive approach for early detection and ongoing monitoring of NBL. Furthermore, the integration of innovative treatment approaches such as CRISPR-Cas9, and cancer stem cell therapy has also been emphasized in this review.

Lung cancer is the foremost cause of cancer-related fatalities globally, and lung adenocarcinoma (LUAD) is one of the common types of lung cancer with significant molecular heterogeneity. Leucine rich repeats and immunoglobulin like domains 1 (LRIG1) has been demonstrated to be down-regulated in lung cancer and related to prognosis of patients. The purpose of this work is to explore the targeting miRNAs of LRIG1, and the related regulatory mechanisms in LUAD. The data of LUAD patients were collected from The Cancer Genome Atlas and Gene Expression Omnibus databases. The differential expression analysis and gene set enrichment analysis (GSEA) were performed using "limma" and "clusterProfiler" function package, respectively. The levels of hsa-miR-21 mRNA and LRIG1 mRNA and LRIG1 protein expressions were analyzed using RT-qPCR and western blot analysis. The infiltration of immune cells was determined using CIBERSORT software. In LUAD patients, hsa-miR-21 expression was observably related to LRIG1 expression. Hsa-miR-21 might negatively modulate the LRIG1 expression in LUAD. LUAD patients with hsa-miR-21 up-regulation exhibited inferior prognosis. In addition, those with LUAD who had high hsa-miR-21 expression but low LRIG1 expression had a worse prognosis, whereas those with low hsa-miR-21 expression but high LRIG1 expression had a better prognosis. Functional enrichment analysis indicated that metabolic related signaling pathways (EGFR tyrosine kinase inhibitor resistance) were significantly activated in LUAD patients with LRIG1 up-regulation. Finally, we found that relative content of naive B cells, plasma cells and resting CD4 + T cells were significantly increased and regulatory T cells and Macrophages M0 were decreased in LRIG1 high expression group and hsa-miR-21 low expression group. We firstly reported that hsa-miR-21 might regulate the LRIG1 expression in LUAD, thereby effecting the onset and progression of LUAD. Clinical trial number: Not applicable.

Lung cancer, the leading cause of cancer-related mortality, has brought exhaled breath condensate (EBC) into focus as a promising non-invasive sample for detecting molecular biomarkers, particularly microRNAs, which regulate gene expression and contribute to tumorigenesis. Ten key studies encompassing approximately 866 subjects consistently demonstrated distinct patterns of miRNA dysregulation in lung cancer. Notably, several reported panels achieved diagnostic sensitivity and specificity exceeding 75% through the identification of distinct miRNA signatures in EBC, with oncogenic miRNAs (e.g., miR-21) upregulated and tumor-suppressor miRNAs (e.g., miR-486) downregulated in lung cancer patients. Analytical advancements, including next-generation sequencing (NGS), have improved miRNA detection sensitivity and specificity, addressing prior limitations of low yield and variability. NGS enabled the identification of novel miRNAs and proved especially effective in overcoming the low RNA yield associated with EBC samples. However, challenges persist regarding standardization of collection, sample dilution, and potential contamination. Moreover, the reproducibility of miRNA signatures across diverse patient populations remains a critical issue. Large-scale, multicenter validation studies are needed to establish robust diagnostic algorithms integrating EBC-derived miRNAs with existing clinical tools. The potential of EBC miRNA profiling to support current screening strategies could significantly improve early lung cancer detection and patient outcomes. Nevertheless, its clinical transition requires further methodological optimization and biomarker validation. This review critically evaluates current evidence on miRNA detection in EBC for lung cancer diagnosis.

Cancer, uncontrolled cell growth due to the loss of cell cycle regulation, is often found to be associated with viral infections and, as recent studies show, with bacterial infections as well. Emerging reports also suggest a strong link between fungi and cancer. The crucial virulence trait of fungi, the switch from yeast (Y) to hyphal (H) form, is found to be associated with carcinogenesis. The physicochemical properties and signal transduction pathways involved in the switch to the hyphal form overlap with those of tumor cell formation. Inhibiting differentiation causes apoptosis in fungi, whereas preventing apoptosis leads to cancer in multicellular organisms. Literature on the fungi-cancer linkage, though limited, is increasing rapidly. This review examines cancer-specific fungal communities, the impact of fungal microbiome on cancer cell progression, similarities between fungal differentiation and cells turning cancerous at biochemical and molecular levels, including the overlaps in signal transduction pathways between fungi and cancer. Based on the available evidence, we suggest that molecules inhibiting the yeast-hyphal transition in fungi can be combined with those targeting tumor cell apoptosis for effective cancer treatment. The review points out fertile research areas where mycologists and cancer researchers can collaborate to unravel common molecular mechanisms. Moreover, antibodies targeting fungal-specific chitin and glucan can be used for the selective neutralization of tumor cells. These new combinations of potential therapies are expected to facilitate the development of target-specific, less harmful and commercially feasible anticancer therapies. We bring together available evidence to argue that fungal infections could either trigger cancer or have a significant role in the development and progression of cancer. Hence, cancer-associated fungal populations could be utilized as a target for a combination therapy involving the integration of anticancer and antifungal drugs as well as inhibitors of fungal morphogenesis to develop more effective anticancer therapies.

Diverse CD4+ T cell subsets with specialized functions operate at different phases of the immune response. Among these are phenotypically and functionally characterized naïve, central memory (CM), effector memory (EM), and regulatory (Treg) cells. Using small RNA-sequencing, we have profiled miRNAs in these cell subsets from healthy subjects and untreated patients with relapsing-remitting multiple sclerosis (RRMS). MiRNA genomic clustering and abundance were also investigated. From the 60 most differentially expressed miRNAs, broad and highly selective core signatures were determined for naïve and memory cells at homeostasis, while miR-146a-5p was strongly upregulated in Treg cells. In line with other studies, a 5-miRNA core was identified for naïve cells (miR-125b-5p, miR-99a-5p, miR-365a-3p, miR-365b-3p, miR-193b-3p). In memory cells, a number of identical miRNAs were more expressed in EM than CM cells, supporting the progressive T cell differentiation model. This was particularly the case for an 8-miRNA core (members from miR-23a∼27a∼24-2, miR-23b∼27b∼24-1, miR-221∼222 clusters, miR-22-3p, miR-181c-5p) and for the large ChrXq27.3 miR-506∼514 cluster. Interestingly, most of these miRNAs were reported to negatively regulate cell proliferation and survival. Finally, we found that the miRNA core signatures of naïve and memory CD4+ T cells were conserved in RRMS patients. Only few miRNAs were quantitatively modified and, among these, miR-1248 was validated to be downregulated in EM cells. Overall, this study expands and provides novel insights into miRNA profiling of CD4+ T cell subsets that may be useful for further investigations.

Multiple sclerosis (MS) is a complex, neurodegenerative and autoimmune disease with a multifactorial etiology. Epigenetic changes can influence the onset and development of the disease, and miRNAs, small RNAs that play a key role in post-transcriptional gene regulation, act as important modulators of the inflammatory process and the central nervous system´s response. The objective of this work is to compare and identify the expression of the miR-143/145 cluster, namely miR-143-5p and miR-145-5p. For this purpose, the expression of two mature miRNAs was determined in the serum of 80 patients with relapsing-remitting multiple sclerosis (RRMS) under different treatments and 60 healthy control subjects (HCS). Total miRNA was isolated from serum and subjected to quantitative PCR analysis (qPCR). In addition, an in silico analysis focused on the molecules affected by the disease was performed. It was found that miR-143-5p is upregulated in patients with RRMS (mean (m)= 0.74) compared to HCS (m = 1.50), while miR-145-5p is significantly downregulated in RRMS (m = 0.32) compared to HCS (m = 2.26). Furthermore, miR-143-5p expression may vary with treatment and exhibit sexual dimorphism, whereas miR-145 expression is primarily pathology-dependent. For in silico analysis, we proposed a new modified C-score that integrates several computational tools. This analysis indicates that GSTM3 and MMP9, which have been previously studied in MS, are the primary targets of miR-143-5p and miR-145-5p, respectively. In conclusion, the differential expression of these miRNAs underscores their possible sensitizing role in pathogenesis, suggesting that these two miRNAs, along with others, may be further explored in unraveling new pathophysiological pathways for treatment response in MS.

MicroRNAs (miRNAs) are classified as small, non-coding RNAs that play crucial roles in diverse biological processes, including cellular development, differentiation, growth, and metabolism. MiRNAs regulate gene expression by recognizing complementary sequences within messenger RNA (mRNA) molecules. Recent studies have revealed that miR-145-5p functions as a tumor suppressor in several cancers, including lung, liver, and breast cancers. Notably, miR-145-5p plays a vital role in the pathophysiology underlying HIV and chronic obstructive pulmonary diseases associated with cigarette smoke. This miRNA is abundant in biofluids and shows potential as a biomarker for the diagnosis and prognosis of several infectious diseases, such as hepatitis B, tuberculosis, and influenza. Additionally, numerous studies have indicated that other non-coding RNAs, including long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), can regulate miR-145-5p. Given the significance of miR-145-5p, a comprehensive overview focusing on its roles in health and disease is essential. This review discusses the dual role of miR-145-5p as a protagonist and antagonist in important human diseases, with particular emphasis on disorders of the respiratory, digestive, nervous, reproductive, endocrine, and urinary systems.

Osteosarcoma (OSa) is the most prevalent primary malignant bone tumor in children and adolescents, characterized by complex genetic and epigenetic alterations. Traditional treatments face significant challenges due to high rates of drug resistance and lack of targeted therapies. Recent advances in microRNA (miRNA) research have opened new avenues for understanding and treating osteosarcoma. This review explores the many critical functions of miRNAs in osteosarcoma, particularly their potential for clinical use. The review highlights two key areas where miRNAs could be beneficial. Firstly, miRNAs can act as biomarkers for diagnosing osteosarcoma and predicting patient prognosis. Secondly, specific miRNAs can regulate cellular processes like proliferation, cell death, migration, and even resistance to chemotherapy drugs in osteosarcoma. This ability to target multiple pathways within cancer cells makes miRNA-based therapies highly promising. Additionally, though the interaction between miRNAs and circular RNAs (circRNAs) falls outside the scope of the paper, it has also been discussed briefly. While miRNA-based therapies offer exciting possibilities for targeting multiple pathways in osteosarcoma, challenges remain. Efficient delivery, potential off-target effects, tumor complexity, and rigorous testing are hurdles to overcome before these therapies can reach patients. Despite these challenges, continued research and collaboration among scientists, clinicians, and regulatory bodies hold the promise of overcoming them. This collaborative effort can pave the way for the development of safe and effective miRNA-based treatments for osteosarcoma.

Breast cancer is the most common invasive cancer diagnosed in females and is also the main cause of cancer-related deaths leading to more than 500,000 deaths annually. The present study aims to identify a promising panel of microRNAs (miRNAs) using bioinformatics analysis, and to clinically validate their utility for diagnosing breast cancer patients with high accuracy in a clinical setting. First, in the in silico phase of our study, using bioinformatics analysis and the data available in the GEO database, miRNAs that were increased in the interstitial fluid of the tumor tissues (differentially expressed miRNAs), were screened and their related target genes were selected. Multimir package of R software was utilized to determine the target genes of the differentially expressed miRNAs (DEMs). The biological functions of discovered genes were analyzed using Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In order to determine the molecular mechanisms behind important signaling pathways and cellular functions, the protein-protein interaction network was built using STRING and Cytoscape software. After that, in the laboratory phase, the expression level of three candidate miRNAs on the serum samples of 26 breast cancer patients and 26 control, as well as 14 tumor tissue samples and 14 adjacent normal tissue samples, has been investigated by Real-time PCR method. Then sensitivity and specificity of candidate miRNAs were evaluated through the ROC curve analysis. After in silico analysis, we revealed that three miRNAs including miR-4443, miR-572, and miR-150-5p were highly increased in the interstitial fluid of breast cancer patients compared to breast cancer tissues. Moreover, our results revealed that the expression level of miR-4443, miR-572, and miR-150-5p were significantly decreased in the serum of breast cancer patients compare to normal controls. Also, the expression level of miR-4443 and miR-150-5p was significantly decreased in the tumor tissue compared to the adjacent non-tumor tissue. Also, ROC curve analysis showed that these three miRNAs have high sensitivity and specificity for the diagnosis of breast cancer patients. Data analysis was conducted with GraphPad Prism software. Our findings suggest the potential utility of measuring tumor-derived miRNAs in serum as an important approach for the blood-based detection of breast cancer patients. It appears that miR-4443, miR-572, and miR-150-5p may serve as promising diagnostic biomarkers with high sensitivity and specificity. However, it's important to note that further research will be needed to definitively establish the use of these miRNAs as potential biomarkers in clinical practice.

MicroRNA-145-5p (miR-145) has been reported to regulate multiple oncogenes and is considered a tumor suppressor. However, it remains unknown whether the level of plasma miR-145 can serve as a risk biomarker for future cancer. Using a population-based cohort (n = 1740) derived from the Trøndelag Health Study (HUNT), we investigated whether plasma miR-145 levels were associated with (1) first life-time cancer, (2) cancer stage at diagnosis, and (3) 2-year all-cause mortality after cancer diagnosis. Cox regression analysis was used to estimate hazard ratios (HR) and 95% confidence intervals (CI). Our findings showed that individuals in the highest quartile of plasma miR-145 levels had a 44% increased risk of developing cancer compared to those in the lowest quartile, independent of age, sex, body mass index, or smoking status (HR 1.44, 95% CI 1.03-2.00 p < 0.05). However, no association was observed between quartiles of miR-145 levels and the risk of being diagnosed with a metastatic cancer, or the risk of 2-year mortality after cancer diagnosis. Our findings suggest that high plasma miR-145 levels are associated with increased cancer risk without affecting the severity of the cancer at diagnosis or affecting the short-term prognosis.

Triple-negative breast cancer (TNBC) is one of the most aggressive and challenging subtypes for treatment, due to the lack of hormone receptors and the human epidermal growth factor receptor 2 (HER2) protein. The identification of new molecular targets is important for the development of targeted and specific therapies for TNBC patients. MicroRNAs (miRNAs) have emerged as promising molecular targets, being involved in cellular processes such as cell survival, apoptosis, differentiation, carcinogenesis, and metastasis. Extracellular vesicles (EVs) have gained prominence in areas such as drug delivery, immune modulation, biomarkers for diagnosis and prognosis, and therapeutics, due to their use as vehicles for the delivery of miRNAs, regulation of gene expression, and development of combined therapeutic strategies. In particular, mesenchymal stem cell-derived EVs (MSC-derived EVs) can transfer proteins, mRNAs/miRNAs, or DNA molecules and are being considered safer treatment options due to their inability to directly form tumors and contain lower amounts of membrane proteins such as MHC molecules. Numerous studies have highlighted the role of miRNAs in EVs in TNBC tumorigenesis, with a focus on diagnosis, prognosis, treatment selection, and monitoring. However, the development of therapies with EVs, especially MSC-derived EVs, is still in its infancy. Therefore, the aim of this review is to address new therapeutic strategies based on the delivery of miRNAs through EVs, with a focus on MSC-derived EVs, for the treatment of TNBC as an innovative therapy in oncology.

The regulation of γ-globin expression is crucial due to its beneficial effects on diseases like β-thalassemia and sickle cell disease. B-cell lymphoma/leukemia 11A (BCL11A) is a significant suppressor of γ-globin, and microRNAs (miRNAs) targeting BCL11A have been shown to alleviate this suppression. In our previous high-throughput sequencing, we identified an 11.32-fold increase in miR-129-5p expression in β-thalassemia patients. However, the regulatory mechanisms of miR-129-5p in the context of erythroid differentiation remain to be elucidated. Our study aimed to elucidate the role of miR-129-5p in γ-globin regulation and erythropoiesis. We measured miR-129-5p levels in peripheral blood from β-thalassemia major and intermedia patients. Fluorescence in situ hybridization, dual-luciferase reporter assays, miRNA pull down assays and western blot analyses were conducted to examine the effects of miR-129-5p on γ-globin expression and BCL11A repression. Cell proliferation, apoptosis, and erythroid differentiation were assessed using cell counting kit-8, Wright-Giemsa, and benzidine staining, and flow cytometry assays. The expression levels of miR-129-5p were significantly elevated in β-thalassemia patients and positively correlated with γ-globin synthesis while negatively correlating with liver damage. miR-129- 5p enhanced γ-globin gene expression in K562 and HUDEP-2 cells by effectively repressing BCL11A. Overexpression of miR-129-5p inhibited cell proliferation, induced cell cycle arrest at the G1/G0 phase, promoted apoptosis and stimulated erythroid differentiation and maturation. Conversely, inhibition of miR-129-5p produced opposite cellular effects. miR-129-5p acts as a positive regulator of erythroid differentiation and γ-globin synthesis. It offers a promising miRNA target for activating the γ-globin gene and reducing ineffective erythropoiesis in β-thalassemia patients.

Bladder carcinoma (BC) is the tenth most frequent malignancy worldwide, with high morbidity and mortality rates. Despite recent treatment advances, high-grade BC and muscle-invasive BC present with significant progression and recurrence rates, urging the need for alternative treatments. The microRNA-21 (miR-21) has superexpression in many malignancies and is associated with cellular invasion and progression. One of its mechanisms of action is the regulation of RECK, a tumor suppressor gene responsible for inhibiting metalloproteinases, including MMP9. In a high-grade urothelial cancer cell line, we aimed to assess if miR-21 downregulation would promote RECK expression and decrease MMP9 expression. We also evaluated cellular migration and proliferation potential by inhibition of this pathway. In a T24 cell line, we inhibited miR-21 expression by transfection of a specific microRNA inhibitor (anti-miR-21). There were also control and scramble groups, the last with a negative microRNA transfected. After the procedure, we performed a genetic expression analysis of miR-21, RECK, and MMP9 through qPCR. Migration, proliferation, and protein expression were evaluated via wound healing assay, colony formation assay, flow cytometry, and immunofluorescence.After anti-miR-21 transfection, miR-21 expression decreased with RECK upregulation and MMP9 downregulation. The immunofluorescence assay showed a significant increase in RECK protein expression (p < 0.0001) and a decrease in MMP9 protein expression (p = 0.0101). The anti-miR-21 transfection significantly reduced cellular migration in the wound healing assay (p < 0.0001). Furthermore, in the colony formation assay, the anti-miR-21 group demonstrated reduced cellular proliferation (p = 0.0008), also revealed in the cell cycle analysis by flow cytometry (p = 0.0038). Our results corroborate the hypothesis that miR-21 is associated with BC cellular migration and proliferation, revealing its potential as a new effective treatment for this pathology.

The diagnostic performance of liquid biopsy-based biomarkers for HCC was comprehensively compared in this network meta-analysis (NMA).

A thorough literature search was conducted to identify all comparative studies from January 1, 2000, to January 11, 2024. The QUADAS-2 tool was utilized to appraise the quality of studies involving diagnostic performance. R (v4.3.3) and an ANOVA model-based NMA were used to assess the diagnostic accuracy of each biomarker.

This study included 82 studies comprising a total of 15,024 patients.CircRNA demonstrated significantly superior performance in distinguishing HCC from healthy populations (superiority index: 3.550 (95% CI [0.143-3])) compared to other diagnostic biomarkers for HCC. "mRNA exhibited significantly superior performance in distinguishing HCC from liver disease patients (superiority index:10.621 (95% CI [7-11])) compared to other diagnostic biomarkers for HCC. Further subgroup analysis of the top-ranking liquid biopsy-based diagnostic biomarkers revealed that hsa_circ_000224 (superiority index: 3.091 (95% CI[0.143-9]) ranked remarkably higher in distinguishing HCC from both healthy populations and liver disease patients. Subgroup analysis of mRNA demonstrated that KIAA0101 mRNA (superiority index: 2.434 (95% CI [0.2-5]) ranked remarkably higher in distinguishing HCC from healthy populations and liver disease patients, respectively.

The results of this meta-analysis show that circRNA and mRNA are the first choice for HCC diagnosis. Subsequent analysis of circRNA and mRNA highlighted hsa_circ_000224, hsa_circ_0003998, KIAA0101 mRNA and GPC-3mRNA as the optimal diagnostic biomarkers for distinguishing HCC from healthy populations and liver disease patients, respectively. Well-structured prospective studies are crucial to comprehensively validate these findings.

https://www.crd.york.ac.uk/PROSPERO/,identifier CRD42024521299.

Mutations in the KRAS gene are well-known tumourigenic drivers of colorectal, pancreatic and lung cancers. Mechanistically, these mutations promote uncontrolled cell proliferation and alter the tumour microenvironment during early carcinoma stages. Given their critical carcinogenic functions, significant progress has been made in developing KRAS inhibitors for cancer treatment. However, clinical applications of these KRAS inhibitor compounds are limited to specific cancer types which carry the relevant KRAS mutations. Additionally, clinical findings have shown that these compounds can induce moderate to serious side effects. Therefore, new approaches have emerged focusing on the development of universal therapeutics capable of targeting a wider range of KRAS mutations, minimising toxicity and enhancing the therapeutic efficacy. This review aims to examine these therapeutic strategies in the context of cancer treatment. It firstly provides an overview of fundamental KRAS biology within the cell signalling landscape and how KRAS mutations are associated with cancer pathogenesis. Subsequently, it introduces the development of current KRAS inhibitors which target certain KRAS mutants in different types of cancer. It then explores the potential of gene therapy approaches, including siRNA, miRNA and CRISPR methodologies. Furthermore, it discusses the use of lipid-based nanocarriers to deliver gene cargos for targeting KRAS gene mutants. Finally, it provides the insights into the future prospects for combatting KRAS mutation-associated cancers.

The cancers of the gastrointestinal (GI) tract have become a common diagnosis worldwide contributing to a large number of mortalities. Though potentially curable they are mostly fatal due to late diagnosis and lack of accurate diagnostic markers. microRNA, micromanagers of gene expression have been associated to have distinct roles as oncogenes or tumour suppressors in several cancers including GI cancers. These miRNAs are known to harbour single nucleotide polymorphisms (SNPs) that lead to loss or gain of its functions and have been found to be associated with altering susceptibility of several cancers. The current study aimed to investigate the role of miRSNPs in common gastrointestinal cancers. A case control study was designed which included 210 GI cancer cases and 230 cancer free controls. The miRSNPs were successfully genotyped using MassARRAY technique. Association analysis revealed that miR-196a; rs11614913, pre-mir-423; rs6505162, pre-mir-605; rs2043556, pre-mir-149; rs2292832 and pri-mir-30c; rs928508 polymorphisms significantly altered the risk of common GI cancers. Multifactor dimensionality reduction analysis demonstrated that miRSNPs alter GI cancer risk by interacting with exposures like diabetes mellitus, alcohol consumption, diet and socioeconomic status in the study subjects. In conclusion it was found that presence of miRNA polymorphism and certain lifestyle factors alters susceptibility to GI cancers significantly.

Astroblastoma is a rare glial neoplasm more frequent in young female patients, with unclear clinical behaviors and outcomes. The diagnostic molecular alteration is a rearrangement of the Meningioma 1 (MN1) gene. MicroRNAs (miRNAs) are important gene expression regulators with strong implications in biological processes. Here, we investigated microRNA expression, regulation, and biological processes correlated to target genes of deregulated miRNAs in MN1-altered astroblastoma.

A cohort of 14 tumor samples, histologically classified as astroblastoma, was retrospectively collected and analyzed through their DNA methylation profiles. MiRNA expression profiles were then detected on MN1-altered astroblastomas (n = 8) and normal brain controls (n = 2) by Nanostring technology and validated by RT-qPCR; then, the expression of deregulated miRNAs was correlated with clinical-pathological characteristics. Subsequently, the methylation status of promoters of deregulated miRNAs was investigated through a methylation profiling microarray. Finally, bioinformatics analysis was conducted to explore the biological processes (BPs) and target genes of differentially expressed miRNAs.

Eight MN-altered astroblastoma were identified. Thirty-nine miRNAs were deregulated in tumor samples compared to normal brain tissue. Downregulated microRNAs exhibited an association with an increased risk of recurrence. The promoter methylation status was investigated in 32/39 miRNAs: 14/32 were epigenetically deregulated. None of them were genetically regulated.

MN1-altered astroblastomas have an miRNA expression signature that identifies specific BPs and pathways. Our findings suggested that the involved pathways could be associated with clinical and pathological characteristics of MN1-altered astroblastomas. Also, the biology of this rare tumor could have potential implications on prognostic markers and therapy.

Considerable epidemiological studies have examined the correlation between polymorphic single-nucleotide variants (SNPs) in miRNA genes and colorectal carcinoma (CRC) risk, yielding inconsistent results. Herein, we sought to systematically investigate the association between miRNA-SNPs and CRC susceptibility by combined evaluation using pairwise and network meta-analysis, the FPRP analysis (false positive report probability), and the Thakkinstian's algorithm.

The MEDLINE, EMBASE, WOS, and Cochrane Library databases were searched through May 2024 to find relevant association literatures. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were computed by the pairwise meta-analysis. Network meta-analysis and the Thakkinstian's method were applied for determining the potentially optimal genetic models; additionally, the FPRP was used to identify noteworthy associations.

Totally, 39 case-control trials involving 18,028 CRC cases, and 21,816 normal participants were included in the study. Eleven SNPs within nine genes were examined for their predisposition to CRC. miR-27a (rs895819) was found to significantly increase CRC risk among overall population (OR 1.58, 95% CI: 1.32-1.89) and Asians (OR 1.62, 95% CI: 1.31-2.01), with the recessive models identified as the optimal models. Furthermore, miR-196a2 (rs11614913), miR-143/145 (rs41291957), and miR-34b/c (rs4938723) were significantly related to reduced CRC risk among Asian descendants under the optimal dominant (OR 0.75, 95% CI: 0.65-0.86), recessive (OR 0.72, 95% CI: 0.60-0.85), and recessive models (OR 0.69, 95% CI: 0.56-0.85), respectively. The results were also proposed by the network meta-analysis or the Thakkinstian's method and confirmed by the FPRP criterion.

The miR-27a (rs895819) is correlated with elevated CRC risk among overall population and Asians, and the recessive model is found to be optimal for predicting CRC risk. Additionally, the miR-196a2 (rs11614913), miR-143/145 (rs41291957), and miR-34b/c (rs4938723), with the dominant, recessive, and recessive models identified as the optimal, might confer protective effects against CRC among Asians.

Publications reveal different outcomes achieved by genetically knocking out a long non-coding microRNA-host-gene (lncMIRHG) versus the administration of pharmacologic antagomirs specifically targeting the guide strand of such intragenic microRNA. This suggests that lncMIRHGs may perform diverse functions unrelated to their role as intragenic miRNA precursors.

This review synthesizes in silico, in vitro, and in vivo findings from our lab and others to compare the effects of knocking out the long non-coding RNA MIR22HG, which hosts miR- 22, versus administering pharmacological antagomirs targeting miR-22-3p.

In silico analyses at the gene, pathway, and network levels reveal both distinct and overlapping targets of hsa-miR-22-3p and its host gene, MIR22HG. While pharmacological antagomirs targeting miR-22-3p consistently improve various metabolic parameters in cell culture and animal models across multiple studies, genetic knockout of MIR22HG yields inconsistent results among different research groups.

Additionally, MIR22HG functions as a circulating endogenous RNA (ceRNA) or "sponge" that simultaneously modulates multiple miRNA-mRNA interactions by competing for binding to several miRNAs.

From a therapeutic viewpoint, genetic inactivation of a lncMIRHG and pharmacologic antagonism of the guide strand of its related intragenic miRNA produce different results. This should be expected as lncMIRHGs play dual roles, both as lncRNA and as a source for primary miRNA transcripts.

Our study aimed to explore the specific functions and potential mechanisms of miR-224-5p in non-small cell lung cancer (NSCLC).

We first analyzed the expression of miR-224-5p in NSCLC patients and cell lines through the GEO database and qRT-PCR analysis. Then, we used MTT assays, wound healing assays, Transwell assays, and western blotting to evaluate the effects of miR-224-5p on NSCLC cell proliferation, migration, invasion, and epithelial-mesenchymal transition (EMT). Furthermore, we used a xenograft tumor model to evaluate the effect of miR-224-5p on NSCLC tumor growth. Potential binding targets of miR-224-5p were further identified through the target prediction databases, and the relationships between miR-224-5p, its targets, and downstream signaling pathways were further verified using luciferase reporter gene assays and western blotting.

The GEO database and qRT-PCR analysis indicated that miR-224-5p was significantly downregulated in NSCLC patients and cell lines. Functional assays indicated that inhibiting miR-224-5p could enhance the proliferation, migration, invasion, and EMT of NSCLC cells, as well as accelerate tumor growth. In contrast, overexpression of miR-224-5p inhibited these processes. We identified IL6ST (interleukin 6 signal transducer) as a binding target of miR-224-5p. We observed that miR-224-5p could bind to and inhibit IL6ST expression and JAK2/STAT3 signaling pathway, and the inhibition of NSCLC tumor growth and JAK2/STAT3 pathway by miR-224-5p could be reversed by IL6ST overexpression.

Our study demonstrated that miR-224-5p inhibited NSCLC by targeting IL6ST, thereby downregulating the JAK2/STAT3 signaling pathway.

Cancer can take years to develop, both at its beginning and during its development. All typical epithelial cancers have a long latency period, sometimes 20 years or more, and if they are clinically detected, distinct genes may include infinite mutations. Long non-coding RNAs (LncRNAs) are a subset of RNAs that regulate many biological processes, including RNA processing, epigenetic control, and signal transduction. Current studies show that lncRNAs, which are dysregulated in cancer, play a significant function in the growth and spread of the illness. LncRNAs have been connected to the overexpression of specific proteins that function in tumors' spread and growth. Moreover, through translational inhibition, microRNAs (miRNAs) regulates gene expression sequence specifically. Apart from that, non-coding RNAs known as miRNAs, with a length of around 22 nucleotides, controls gene expressions in a sequence-specific way either by preventing translation or degrading messenger RNA (mRNA). Quercetin appears to have a significant role in altering miRNA and lncRNA expression, which is linked to variations in the production of oncogenes, tumor suppressors, and proteins produced from cancer. Quercetin may change the earliest epigenetic modifications related to cancer prevention in addition to its usual antioxidant or anti-inflammatory effects. It would be beneficial to have more in-depth information on how Quercetin modulates miRNAs and lncRNAs to use it as a cancer therapeutic strategy. Here, we go through what is known about Quercetin's potential to modulate miRNAs and lncRNAs in various malignancies.

Non-coding RNAs (ncRNAs), specifically MicroRNAs or miRNAs, are now understood to be essential regulators in the complex field of gene expression. By selectively binding to certain mRNA targets, these tiny RNA molecules control the expression of genes, leading to mRNA degradation or translational repression. The discovery of miRNAs has significantly advanced biomedical research, particularly in elucidating the molecular mechanisms underlying various diseases and exploring innovative therapeutic approaches. Recent progress in miRNA research has provided insights into their biogenesis, functional roles, and potential clinical applications. Despite the absence of established methodologies for clinical implementation, miRNAs show great promise as diagnostic and therapeutic agents for a wide array of diseases. Their distinctive attributes, such as high specificity, sensitivity, and accessibility, position them as ideal candidates for biomarker development and targeted therapy. Achieving a comprehensive understanding of miRNA biology and functionality is crucial to fully harnessing their potential in medicine. Ongoing research efforts aim to unravel the intricate mechanisms of miRNA-mediated gene regulation and to develop novel approaches for utilizing miRNAs in disease diagnosis, prognosis, and treatment. This review provides a comprehensive analysis of current knowledge on miRNAs, focusing on their biogenesis, regulatory mechanisms, and potential clinical applications. By synthesizing existing evidence and highlighting key research findings, this review aims to inspire further exploration into the diverse roles of miRNAs in health and disease. Ultimately, this endeavour could result in the development of innovative miRNA-based diagnostic and therapeutic strategies.

Recently, microRNAs (miRNAs) have been applied as biomarkers for diffuse large B-cell lymphoma (DLBCL) patients. Early diagnosis and management of DLBCL can improve patient survival and prognosis.

This systematic review and meta-analysis aimed to evaluate the diagnostic and prognostic accuracy of miRNA biomarkers in DLBCL patients.

We used the keywords "diffuse large B-cell lymphoma" and "microRNA" to search databases for original publications until June 14, 2023. Specificity, sensitivity, and AUC were used to assess diagnostic accuracy, and the prognostic value was assessed using the overall survival (OS) and progression-free survival (PFS) hazard ratio (HR). A subgroup analysis was performed based on the sample type acquired to investigate the heterogeneity.

Thirteen diagnostic and 33 prognostic studies were included from 839 articles. The Reitsma bivariate model estimated a sensitivity of 0.788 (95% CI: 0.733-0.834, p < 0.001), a specificity of 0.727 (95% CI: 0.654-0.790, p < 0.001), and an AUC of 0.824 in. The pooled AUC was 0.7385 (95% CI: 0.6847-0.7923, p < 0.0001). The pooled OS and PFS HRs (> 1) were 2.2847 (95% CI: 1.7248-3.0263, p < 0.0001) and 2.4883 (95% CI: 1.7367-3.5650, p < 0.0001). The pooled OS and PFS HRs (< 1) were 0.4965 (95% CI: 0.3576-0.6894, p < 0.0001) and 2.4883 (95% CI: 1.7367-3.5650, p < 0.0001). MiR-155 diagnostic values had a sensitivity of 0.710 (p > 0.1) and a specificity of 0.725 (p < 0.05), with an AUC of 0.776. miR-21 diagnostic values had an AUC of 0.8468 (p < 0.0001) and OS HR of 2.8938.

MicroRNAs could serve as a powerful diagnostic and prognostic tool in DLBCL.

Triple-negative breast cancer (TNBC) is a highly aggressive and clinically challenging subtype of breast cancer, lacking the expression of estrogen receptor (ER), progesterone receptor (PR), and HER2/neu. The absence of these receptors limits therapeutic options necessitating the exploration of novel treatment strategies. Epigenetic modifications, which include DNA methylation, histone modifications, and microRNA (miRNA) regulation, play a pivotal role in TNBC pathogenesis and represent promising therapeutic targets. This review delves into the therapeutic potential of epigenetic interventions in TNBC, with a focus on DNA methylation, histone modifications, and miRNA therapeutics. We examine the role of DNA methylation in gene silencing within TNBC and the development of DNA methylation inhibitors designed to reactivate silenced tumor suppressor genes. Histone modifications, through histone deacetylation and acetylation in particular, are critical in regulating gene expression. We explore the efficacy of histone deacetylase inhibitors (HDACi), which have shown promise in reversing aberrant histone deacetylation patterns, thereby restoring normal gene function, and suppressing tumor growth. Furthermore, the review highlights the dual role of miRNAs in TNBC as both oncogenes and tumor suppressors and discusses the therapeutic potential of miRNA mimics and inhibitors in modulating these regulatory molecules to inhibit cancer progression. By integrating these epigenetic therapies, we propose a multifaceted approach to target the underlying epigenetic mechanisms that drive TNBC progression. The synergistic use of DNA methylation inhibitors, HDACi, and the miRNA-based therapies offers a promising avenue for personalized treatment strategies, aiming to enhance the clinical outcome for patients with TNBC.

Gastrointestinal stromal tumors, the most prevalent mesenchymal tumors (80 %) of the gastrointestinal tract, comprise less than 1 % of all gastrointestinal neoplasms and about 5 % of all sarcomas. Despite their rarity, Gastrointestinal stromal tumors present diverse clinical manifestations, anatomic locations, histological subtypes, and prognostic outcomes.

This scoping review comprehensively explores the epidemiology, clinical characteristics, diagnostic and prognostic modalities, as well as new therapeutic options for Gastrointestinal stromal tumors.

A particular focus is placed on the promising role of bio-nanomaterials as multifunctional agents for drug delivery and 3D tumor microenvironment modeling. Bio-nanomaterials offer promising opportunities for targeted drug delivery, overcoming treatment resistance, and improving therapeutic efficacy.

Despite significant advancements, Gastrointestinal stromal tumors remain a complex clinical entity with ongoing challenges. The integration of nanotechnology into Gastrointestinal stromal tumors management offers the potential to enhance patient outcomes. Future studies should prioritize the development and evaluation of nanomaterial-based therapies in clinical trials to facilitate the translation of laboratory discoveries into real-world clinical applications.

Breast cancer (BC) remains a significant global health issue, necessitating advanced molecular approaches for early detection and prevention. This review delves into the roles of microRNAs (miRNAs) and circular RNAs (circRNAs) in BC, highlighting their potential as non-invasive biomarkers. Utilizing in silico tools and databases, we propose a novel methodology to establish mRNA/circRNA/miRNA axes possibly indicative of early detection and possible prevention. We propose that during early tumor initiation, some changes in oncogene or tumor suppressor gene expression (mRNA) are mirrored by alterations in corresponding circRNAs and reciprocal changes in sponged miRNAs affecting tumorigenesis pathways. We used two Gene Expression Omnibus (GEO) datasets and identified five mRNA/circRNA/miRNA axes as early possible tumor initiation biomarkers. We further validated the proposed axes through a Kaplan-Meier (KM) plot and enrichment analysis of miRNA expression using patient data. Evaluating coupled differential expression of circRNAs and miRNAs in body fluids or exosomes provides greater confidence than assessing either, with more axes providing even greater confidence. The proposed methodology not only improves early BC detection reliability but also has applications for other cancers, enhancing preventive measures.

miRNAs play a critical role in the progression of various diseases, including oral squamous cell carcinoma (OSCC), which represents a major health concern and is one of the leading causes for new cancer cases worldwide. The miRNA dysregulation causes havoc and could be attributed to various factors, with epigenetic silencing of tumor suppressor genes being a major contributor to tumorigenesis. In this study, we have explored the tumor suppressive role of miR-198 in OSCC.

The tumor suppressive effect of miR-198 is established using miRNA analysis in OSCC cell lines, patient samples and xenograft nude mice model. The relationship between the miR-198 and TOPORS is explored using bioinformatics analyses, qRT-PCR, dual-luciferase reporter assay, Western blotting and cancer hall marks assays. The hypermethylation of the MIR198 promoter is confirmed using bisulfite sequencing PCR.

We have found miR-198 to be upregulated in OSCC cells treated with 5-Azacytidine, a known DNA methyltransferase inhibitor. Upregulation of miR-198 in 5-Azacytidine treated OSCC cells appears to be due to methylation of the MIR198 promoter. Using bioinformatics analysis and dual-luciferase reporter assay, we have identified TOPORS (TOP1 binding arginine/serine rich protein, E3 ubiquitin ligase) as a novel gene target for miR-198. miR-198-mediated repression of TOPORS decreases cell proliferation and anchorage-independent growth and enhances apoptosis of OSCC cells, which is dependent on the presence of the 3'UTR in TOPORS. An inverse correlation between the expression levels of miR-198 and TOPORS is observed in OSCC patient samples, highlighting the biological relevance of their interaction. Delivery of a synthetic miR-198 mimic to OSCC cells results in a significant decrease in xenograft size in nude mice, potentiating its use in therapeutics.

These results suggest that miR-198 is epigenetically silenced in OSCC, which promotes tumor growth, in part, by upregulating the levels of TOPORS.

In recent years, germline mutations in the microRNA (miRNA) processor genes DICER1 and DGCR8 have been coupled to the development of thyroid follicular nodular disease (TFND), thereby casting new light on the etiology of this enigmatic, benign condition in non-iodine-deficient regions. Moreover, DICER1 and DGCR8 mutations have also been reported in rare subsets of follicular cell-derived thyroid carcinomas. Specifically, truncating germline or missense somatic DICER1 mutations have been reported in small subsets of pediatric and adolescent follicular thyroid carcinoma (FTC) and poorly differentiated thyroid carcinoma (PDTC). Similarly, a recurrent somatic mutation of the DGCR8 gene has been observed in highly aggressive FTCs and in some indolent cases of encapsulated follicular variant of papillary thyroid carcinoma. The reason why identical mutations in the same miRNA processor gene can lead to such a myriad of thyroid conditions, ranging from benign TFND to FTCs and PDTCs, remains unclear. This review highlights key features of miRNA regulator gene mutations in thyroid disease and explores their potential roles as drivers or progression events in tumor development.

Canine mammary tumors (CMTs) represent a significant health concern in dogs, with a high incidence among intact female dogs. CMTs are a promising comparative model for human breast cancer, due to sharing several pathophysiological features. Additionally, CMTs have a strong genetic correlation with their human counterpart, including the expression of microRNAs (miRNAs). MiRNAs are a class of non-coding RNAs that play important roles in post-translational regulation of gene expression, being implicated in carcinogenesis, tumor progression, and metastasis. Moreover, miRNAs hold promise as diagnostic, prognostic, and metastatic biomarkers. Understanding the molecular mechanisms underlying CMTs is crucial for improving diagnosis, prognosis, and monitoring of treatments. Herein, we provide a comprehensive overview of the current knowledge on miRNAs in CMTs, highlighting their roles in carcinogenesis and their potential as biomarkers. Additionally, we highlight the current limitations and critically discuss the overarching challenges in this field, emphasizing the need for future research to translate miRNA findings into veterinary clinical practice.

Granzyme activity can affect the processing and stability of miRNAs within target cells. They also could induce changes in miRNA expression that impact apoptotic signaling. Granzyme-induced apoptosis might result in changes to the miRNA profile, which can further influence the apoptosis and inflammation processes.

The aim of this study was to bioinformatically analyze which miRNAs and transcription factors bind to the CDS and UTR regions of the granzyme family to regulate gene expression in relation to granzyme evolution and their association with human cancer diseases.

The expression patterns of granzyme genes were analyzed in various human tissues. MiRNAs binding to the CDS and UTR of the granzyme family were examined, and the transcription factors binding to these miRNAs binding sites were also analyzed. Cytoscape program was used to visualize and analyze the networks of interactions between granzyme mRNA and miRNAs. Additionally, the evolutionary patterns of the granzyme family in relation to miRNAs and transcription factors binding were investigated.

Analysis of the expression patterns of the granzyme family in various human tissues shows that GZMA and GZMK are strongly expressed in lymph nodes. GZMB exhibits strong expression in the bone marrow, while GZMA is prominently expressed in the spleen. Twenty-two miRNAs bind to both GZMK and GZMB mRNA, while six miRNAs bind to both GZMK and GZMM mRNA. The only miRNA that binds to GZMK, GZMB, GZMM, and GZMA mRNA is hsa-miR-146a-5p. Transcription factors JUND, FOS, and JUN are distinctly interconnected with has-miR-5696 and GZMK. Association data between the granzyme family and cancers showed that various miRNAs were consistently implicated and exhibited either upregulation or downregulation.

Although the granzyme family possesses distinct genetic information, it shows relatively high expression levels in the lymph node, spleen, and bone marrow. Many miRNAs specifically regulate granzyme gene expression, and various transcription factors are involved. Analyzing the granzyme genes-miRNAs-transcription factors-related network will provide crucial insights into the mechanisms of cancer development and suppression.

Non-coding RNAs (ncRNAs), especially microRNAs (miRNAs) and long ncRNAs (lncRNAs), are essential regulators of processes, such as the cell cycle and apoptosis. In addition to interacting with intracellular complexes and participating in diverse molecular pathways, ncRNAs can be used as clinical diagnostic biomarkers and therapeutic targets for fighting cancer. Studying ncRNA gene clusters is crucial for understanding their role in cancer and developing new treatments. LOC124905135 is a protein-coding gene encoding a collagen alpha-1(III) chain-like protein, and also acts as a gene for several ncRNAs, including miR-3619, PRR34 antisense RNA 1 (PRR34-AS1), PRR34, long intergenic ncRNA 2939 (LINC02939), LOC112268288, and MIRLET7BHG. It also serves as a host gene for three miRNAs (hsa-let7-A3, hsa-miR-4763, and hsa-let-7b). Notably, the ncRNAs derived from this particular genomic region significantly affect various cell functions, including the cell cycle and apoptosis. This cluster of ncRNAs is dysregulated in several types of cancer, exhibiting mutations, alterations in copy number, and being subject to DNA methylation and histone modification. In summary, the ncRNAs derived from the LOC124905135 cluster could be used as targets for diagnosis, therapy monitoring, and drug discovery in human cancers.