Colorectal cancer is a major global health burden, with significant heterogeneity in clinical outcomes among patients. Identifying robust prognostic gene expression signatures can help stratify patients, guide treatment decisions, and improve clinical management. This review provides an overview of current prognostic gene expression profiles in colorectal cancer research. We have synthesized evidence from numerous published studies investigating the association between tumor gene expression patterns and patient survival outcomes. The reviewed literature reveals several promising gene signatures that have demonstrated the ability to predict disease-free survival and overall survival in CRC patients, independent of standard clinicopathological risk factors. These genes are crucial in fundamental biological processes, including cell cycle control, epithelial-mesenchymal transition, and immune regulation. The implementation of prognostic gene expression tests in clinical practice holds great potential for enabling more personalized management strategies for colorectal cancer.

Tumors are associated with the highest mortality rates worldwide. For more than a decade, research has focused on the genetic involvement of proteins in cancer; however, a complete class of molecular non‑coding (nc)RNAs have been discovered in recent years, and these are considered to be associated with cancer. Notably, ncRNAs are highly conserved and multifunctional. These interact with multiple signaling pathways, influencing cell cycle progression and various physiological processes. Therefore, the present review aimed to investigate ncRNA, microRNA, transfer RNA‑derived small RNA, PIWI‑interacting RNA and long non‑coding RNA to further understand the associated generation processes, functional mechanisms and therapeutic roles in tumors. The present review demonstrated the critical role of ncRNAs in tumors, and may provide a novel theoretical basis for the role of ncRNAs as biomarkers or therapeutic tools in the treatment of cancer.

Non-coding accounts for 98 %-99 % of the human genome and performs many essential regulatory functions in eukaryotes, involved in cancer development and development. Non-coding RNAs are abundantly enriched in exosomes, which play a biological role as vectors. Some biofunctional non-coding RNAs are specifically designed as exosomes for the treatment of cancers such as glioma. Glioma is one of the most common primary tumors within the skull and has varying degrees of malignancy and histologic subtypes of grades I-IV. Gliomas are characterized by high malignancy and an abundant blood supply due to rapid cell proliferation and vascularization, often with a poor prognosis. Exosomal non-coding RNAs can be involved in the tumorigenesis process of glioma from multiple directions, such as angiogenesis, tumor proliferation, metastatic invasion, immune evasion, apoptosis, and autophagy. Therefore, non-coding RNAs in exosomes are suitable as markers or therapeutic targets for early diagnosis of diseases and for predicting the prognosis of a variety of diseases. Regulating exosome production and the level of exosomal non-coding RNA expression may be a new approach to prevent or eliminate glioma. In this review, we review the origin and characteristics of exosomal non-coding RNAs, and introduce the functional studies of exosomal non-coding RNAs in glioma and their potential clinical applications, in order to broaden new ideas for the treatment of glioma.

MicroRNAs (miRs) have emerged as pivotal regulators in the development and progression of colorectal cancer (CRC), and MicroRNA-206 (miR-206) has garnered attention as a potentially influential factor. However, the specific biological functions and complete mechanistic understanding of miR-206 in CRC remain largely uncharacterized. This study aims to bridge this research gap by providing a comprehensive analysis of miR-206's role in CRC. An exploration of the molecular mechanisms regulated by miR-206, its intricate interplay with target genes, and its significant impact on cellular processes highlights its potential utility as both a diagnostic marker and a therapeutic target. The significance of this research lies in potentially enabling the development of innovative therapeutic approaches, ultimately aiming to improve prognosis and survival rates in CRC patients by elucidating the functions of miR-206. Critical pathways, such as c-Met and PTEN/AKT, play crucial roles within the regulatory network of miR-206 in CRC and impact various cellular processes involved in CRC pathogenesis, metastasis, and treatment response. Understanding the complex interactions between miR-206 and key signaling pathways like c-Met and PTEN/AKT is crucial for understanding the underlying mechanisms driving CRC initiation and progression. This knowledge can inform the development of targeted therapeutic interventions, potentially leading to improved patient outcomes and advances in CRC management.

Dilated cardiomyopathy (DCM) is a major cause of heart failure (HF) defined by ventricular dilatation and systolic dysfunction. Although microRNAs (miRNAs) are known to affect HF development, little is known about the contribution of genetic variants in miRNAs or their precursors to the susceptibility or pathogenesis of DCM. We screened 1640 DCM cases for variants in cardiac miR-208a and miR-208b and their precursors. We identified four variants in the miR-208a pre-miRNA, which are present at very low frequencies in the general population. Two of these variants (+42G > T and +68G > T) alter a highly conserved nucleotide and the predicted pre-miRNA secondary structure. Both variants result in reduced mature miR-208a levels in overexpression experiments. The variant +42G > T also increased pre-miR-208a levels in these experiments, which indicates a maturation deficiency. Co-transfection of the overexpression constructs with a luciferase construct containing six miRNA binding sites revealed that both variants also impair repression of luciferase expression by miR-208a, indicative of also a loss of miR208a function. Together this indicates that these DCM-associated variants impair formation of mature miR208a. Combined with the role of miR-208a in cardiac contractility this suggests that variants +42G > T and +68G > T in pre-miR-208a may contribute to the DCM phenotype observed in these patients.

Cancer is a formidable adversary in contemporary healthcare. Routine screening and early diagnosis are crucial for favourable therapeutic outcomes. Publications, clinical trials, and patent landscape analysis suggest miRNA as promising biomarkers for diagnosis and prognosis of various cancers. This review intends to shed a holistic view of the current and futuristic methods for electrochemical biosensing platforms, using miRNA as biomarkers, coupled with microfluidics, machine learning techniques, and portable electronic devices. Electrochemical biosensors are thoroughly reviewed as they are promising candidate in the design and development of such devices where there is an in-depth exploration of the existing molecular techniques and sophisticated electrochemical biosensing strategies developed for the detection of miRNAs. Additionally, the review will critically analyze diverse signal enhancement strategies and microfluidic platforms specifically tailored for the detection of miRNA. Practical examples of such integrated electrochemical microfluidic biosensors are thoroughly cited along with the prospect of integration of these techniques with portable electronics, highlighting the future potential of highly integrated and accessible diagnostic solutions. Furthermore, the review will also encompass an assessment of the ongoing clinical trials investigating the utility of miRNA as cancer biomarker in diagnostic settings. Moreover, by assessing existing patents, the review shall provide a nuanced understanding of the intellectual property landscape, identifying key players, emerging technologies, and potential future directions. Our review with a 360-degree updated view on molecular biology components, electrochemical biosensors, engineering device design, clinical trials and patent landscape would appeal to researchers, engineers and clinicians working in the area of cancer molecular diagnosis.

The tumor micro-environment is a key determinant for promoting cancer cell growth and development with exosomal miRNAs emerging as key regulators of tumor growth and metastasis. miR16 is one well-established tumor suppressor miRNAs that induces apoptosis, while inhibiting angiogenesis and inflammation across various cancers. Herein, we investigated the role of exosomal miR16 in the cervical cancer microenvironment and its underlying molecular mechanisms. We treated human cervical cancer HeLa cells with Allyl Isothiocyanate (AITC) and observed the impact of miR16-enriched exosomes on human fibrosarcoma HT1080 cells. We found a significant increase of miR16 expression in AITC-treated HeLa cells and purified exosomes. When the exosomes were cultured with fibroblasts, miR16 expression was increased in fibroblast cells. Treatment with AITC-exposed HeLa exosomes induced increased Bax/Bcl2 ratio and downregulated PCNA, HIF-1α, SDF-1α, IL-6, and p22phox expression in fibroblasts. Remarkably, the knockdown of miR16 in fibroblasts inhibited the AITC-induced increase in the Bax/Bcl2 ratio and restored VEGF, PCNA, HIF-1α, SDF-1α, IL-6, and p22phox expression. In sum, our findings demonstrate the potential of AITC-mediated exosomal miR16 enrichment as an effective approach to inhibit cancer growth and development, and reveal a new potential for cancer management and therapy.

Non-coding RNAs play crucial roles in disease initiation and progression, making them promising biomarkers for early diagnosis and treatment monitoring. Conventional nucleic acid diagnostic methods, including polymerase chain reaction (PCR), next-generation sequencing (NGS), and enzyme-linked immunosorbent assay (ELISA), alongside emerging techniques such as single-molecule fluorescence in situ hybridization (smFISH), nanopore sequencing, and single-cell RNA sequencing (scRNA-seq), face inherent limitations in detecting regulatory non-coding RNAs. These challenges include laborious workflows, prolonged processing times, and technical complexities, hindering their broad applicability in rapid and high-throughput RNA analysis. CRISPR/Cas13a-based biosensors, integrated with various signal transduction systems-such as fluorescence, electrochemistry, colorimetry, surface-enhanced Raman spectroscopy (SERS)-show great promise for real-world diagnostic applications. This review provides a comprehensive overview of the CRISPR/Cas13a-mediated RNA detection mechanism, the development of CRISPR/Cas13a-based biosensors, and their integration with innovative signal detection methods. Additionally, we highlight the progress in portable detection devices, including lateral flow assay strips and smartphone-based platforms. Finally, the review discusses the current challenges and future prospects of CRISPR/Cas13a-based biosensors, particularly in the context of clinical diagnostics and personalized medicine.

Ischemic stroke (IS) is the leading cause of long-term disability and the second leading cause of death worldwide. It remains a significant clinical problem because only supportive therapies exist, such as thrombolytic agents and surgical thrombectomy, which do not restore function. Understanding the molecular pathogenesis of IS, including dysfunction in oxidative homeostasis, apoptosis, neuroinflammation and neuroprotection, is crucial to developing therapies. Non-coding RNAs (ncRNAs) are master regulators, and one ncRNA that stands out is miR-155, a pro-inflammatory micro-RNA elevated in stroke. This review addresses the biological mechanisms reported in the literature that support using miR-155 as a biomarker and therapeutic agent to treat IS in patients.

This review explores the dual role of miR-195 in cancer, acting as both a tumor suppressor and, in specific contexts, a tumor promoter. It highlights its molecular mechanisms, focusing on key signaling pathways such as Wnt-1/β-catenin, VEGF/VEGFR, and PI3K/AKT/mTOR, as well as its involvement in competitive gene regulation. The clinical potential of miR-195 in cancer screening, diagnosis, prognosis, and therapy is examined, particularly its ability to enhance therapeutic efficacy and reduce recurrence risk when combined with chemotherapy or immunotherapy. Despite these promising aspects, challenges such as precise regulation, efficient delivery systems, and clinical translation remain. Future research should prioritize advancing miR-195's integration into personalized medicine, immunotherapy, and novel delivery technologies, aiming to establish it as a reliable biomarker and therapeutic target for improved cancer care.

The microRNA miR-126 supports endothelial cells and blood vessel integrity. Recent research has shown that it also serves as a key link between exercise and cancer. This article delves into how exercise affects the expression of miR-126, impacting cardiovascular well-being and metabolic control. The article also examines the various contributions of miR-126 in cancer, acting as both a suppressor and an enhancer depending on the particular context. Regular aerobic exercises, including HIIT, consistently increase levels of miR-126, leading to enhanced angiogenesis, endothelial repair, and improved vascular function through mechanisms involving VEGF, HIF-1α, and EPC mobilization. Resistance training affects similar pathways, but does not cause a significant change in miR-126 levels.MiR-126 involves in cancer by suppressing tumor growth and controlling key pathways such as PI3K/Akt, ERK/MAPK, and EMT. Lower levels are associated with negative outcomes, later stages of the disease, and increased spread of different types of cancer like glioblastoma, CRC, ovarian, esophageal, gastric, and prostate cancer.The relationship between exercise and cancer suggests a possible therapeutic approach, where the regulation of miR-126 through exercise could help improve vascular function and slow tumor growth. Further studies should focus on understanding the specific molecular pathways through which miR-126 connects these areas, leading to potential interventions that utilize its regulatory network to promote cardiovascular well-being and enhance cancer treatment.

The 2024 Nobel Prize honored groundbreaking microRNA (miRNA) discoveries that unveiled the critical functions of miRNAs in fundamental biology and human health. Despite promising therapeutic potential, there are no Food and Drug Administration (FDA)-approved miRNA-based cancer therapies. This commentary discusses the progress and challenges of miRNA-based cancer therapeutics and their potential impact on future clinical oncology.

Breast cancer is the primary cause of cancer-related death and the most frequent malignancy among women in Western countries. Although there have been advancements in combination treatments and targeted therapies for the metastatic diseases management, metastatic breast cancer is still the second most common cause of cancer-related deaths among U.S. women. The routes of metastasis encompass invasion, intravasation, circulation, extravasation, infiltration into a remote location to establish a metastatic niche, and the formation of micro-metastases in a new environment. Each of these processes is regulated by changes in gene expression. MicroRNAs (miRNAs) are widely expressed by a variety of organisms and have a key role in cell activities including suppressing or promoting cancer through regulating various pathways. Target gene expression is post-transcriptionally regulated by miRNAs, which contribute to the development, spread, and metastasis of breast cancer. In this study, we comprehensively discussed the role of miRNAs as predictors of breast cancer metastasis, their correlation with the spread of the disease to certain organs, and their potential application as targets for breast cancer treatment. We also provided molecular mechanisms of miRNAs in the progression of breast cancer, as well as current challenges in miRNA-based therapeutic approaches. Furthermore, as one of the primary issues with the treatment of solid malignancies is the efficient delivery of miRNAs, we examined a number of cutting-edge carriers for miRNA-based therapies and CRISPR/Cas9 as a targeted therapy for breast cancer.

Noncoding RNAs (ncRNAs) are a heterogeneous group of RNA molecules whose classification is mainly based on arbitrary criteria such as the molecule length, secondary structures, and cellular functions. A large fraction of these ncRNAs play a regulatory role regarding messenger RNAs (mRNAs) or other ncRNAs, creating an intracellular network of cross-interactions that allow the fine and complex regulation of gene expression. Altering the balance between these interactions may be sufficient to cause a transition from health to disease and vice versa. This leads to the possibility of intervening in these mechanisms to re-establish health in patients. The regulatory role of ncRNAs is associated with all cancer hallmarks, such as proliferation, apoptosis, invasion, metastasis, and genomic instability. Based on the function performed in carcinogenesis, ncRNAs may behave either as oncogenes or tumor suppressors. However, this distinction is not rigid; some ncRNAs can fall into both classes depending on the tissue considered or the target molecule. Furthermore, some of them are also involved in regulating the response to traditional cancer-therapeutic approaches. In general, the regulation of molecular mechanisms by ncRNAs is very complex and still largely unclear, but it has enormous potential both for the development of new therapies, especially in cases where traditional methods fail, and for their use as novel and more efficient biomarkers. Overall, this review will provide a brief overview of ncRNAs in human cancer biology, with a specific focus on describing the most recent ongoing clinical trials (CT) in which ncRNAs have been tested for their potential as therapeutic agents or evaluated as biomarkers.

The origins of immunosuppression, neutropenia, and anemia in patients with chronic lymphocytic leukemia (CLL) are not fully understood. Because in patients with CLL, circulating exosomes, which participate in cell-to-cell interactions, are CLL cell-derived, we examined whether those exosomes contribute to abnormal features of this disease. Our data revealed that CLL cell-derived exosomes engulfed by healthy donors' monocytes, fibrocytes, and lymphocytes altered target-cell gene and protein expression and suppressed normal hematopoiesis. CLL cell-derived exosomes increased normal monocytes' CD14 and CD16 expression such that it mimicked the accessory-cell profile and upregulated T cells' checkpoint PD-1 and CD160 protein levels, potentially reducing T-cell-mediated anti-CLL activity. In normal B cells, CLL cell-derived exosomes induced apoptosis and CD5 expression, suggesting that CLL cell-derived exosomes eliminate B cells and not all CD19+/CD5+ cells in CLL patients are clonal. RNA sequencing and quantitative real-time PCR revealed that CLL cell-derived exosomes harbored RNAs of pro-apoptotic genes and genes that increase metabolism, induce proliferation, and induce constitutive PI3K-mTOR pathway activation. CLL cell-derived exosomes inhibited hematopoietic progenitor proliferation, hindering the supportive effect of monocyte-derived fibrocytes. Together, our findings suggest that CLL cell-derived exosomes disrupt the immune and hematopoietic systems and contribute to disease progression in patients with CLL.

Advanced laryngeal squamous cell carcinoma (LSCC) is the second most prevalent type of head and neck squamous cell carcinoma (HNSCC). Identifying microRNAs (miRNAs) related to key regulatory molecules or mechanisms could offer an alternative approach to developing new treatment strategies. The aim of our study is to evaluate significant correlations among deregulated miRNAs in advanced laryngeal carcinoma and to analyze, in silico, their strength of association, targets, and the most deregulated pathways. Several miRNAs demonstrated promising co-expression results, specifically miR-93-5p, miR-145-5p, and miR-210-3p. Their expressions were explored and further validated in a large set of in vivo advanced LSCC samples, which were subsequently used for bioinformatics and enrichment analyses. Our results highlight the significant roles of miR-93-5p, miR-145-5p, and miR-210-3p in regulating major pathways linked to the cell cycle via epithelial-to-mesenchymal transition (EMT), PI3K/Akt signaling, hypoxia, metabolism, apoptosis, angiogenesis, and metastasis. The associations between the expressions of these miRNAs and patients' clinical features could be central to the progression of advanced LSCC. Overall, our study provides important insights into the co-expression and regulatory networks of miR-93-5p, miR-145-5p, and miR-210-3p in advanced laryngeal carcinoma, underscoring their potential as therapeutic targets or biomarkers for this aggressive cancer. Further research is needed to elucidate the specific mechanisms through which these miRNAs contribute to the pathogenesis and progression of laryngeal carcinoma.

MicroRNA expression is frequently suppressed in cancer, and previously we demonstrated coordinate downregulation of multiple related microRNAs of the miR-15/107 group in malignant pleural mesothelioma (PM). From an alignment of the miR-15 family and the related miR-103/107, we derived a consensus sequence and used this to generate synthetic mimics. The synthetic mimics displayed tumour suppressor activity in PM cells in vitro, which was greater than that of a mimic based on the native miR-16 sequence. These mimics were also growth inhibitory in cells from non-small cell lung (NSCLC), prostate, breast and colorectal cancer, and sensitised all cell lines to the chemotherapeutic drug gemcitabine. The increased activity corresponded to enhanced inhibition of the expression of target genes and was associated with an increase in predicted binding to target sites, and proteomic analysis revealed a strong effect on proteins involved in RNA and DNA processes. Applying the novel consensus mimics to xenograft models of PM and NSCLC in vivo using EGFR-targeted nanocells loaded with mimic led to tumour growth inhibition. These results suggest that mimics based on the consensus sequence of the miR-15/107 group have therapeutic potential in a range of cancer types.

MicroRNA (miRNA/miR)‑100 is a crucial tumor‑suppressive miRNA that serves a pivotal role in the initiation and progression of various malignancies. miR‑100 regulates cancer cell proliferation, migration, invasion and apoptosis by targeting oncogenes, and acts as a molecular sponge to regulate long non‑coding RNAs and circular RNAs, thereby influencing processes such as glycolysis, autophagy and resistance to chemotherapy/radiotherapy. Furthermore, miR‑100 suppresses tumor progression by modulating key signaling pathways, including the PI3K/AKT and Wnt/β‑catenin signaling pathways. miR‑100 exhibits potential for early cancer diagnosis, particularly in cancer types such as gastric and lung cancer, where it can serve as a non‑invasive biomarker for early screening. As a therapeutic target, restoring miR‑100 expression can enhance the efficacy of chemotherapy or targeted therapy, thereby improving patient prognosis. Although challenges remain in its clinical application, including delivery systems and safety concerns, ongoing research suggests that miR‑100 holds promise for personalized treatment and early diagnosis. Given that cancer remains a global health challenge, research on miR‑100 provides hope for cancer therapy, particularly in China, where the mortality rates of malignancies such as gastric, lung and liver cancer continue to rise, further emphasizing its potential for clinical translation.

Cell cycle progression and leukemia development are tightly regulated processes in which even a small imbalance in the expression of cell cycle regulatory molecules and microRNAs (miRNAs) can lead to an increased risk of cancer/leukemia development. Here, we focus on the study of a ubiquitous, multifunctional, and oncogenic miRNA-hsa-miR-155-5p (miR-155, MIR155HG), which is overexpressed in malignancies including chronic lymphocytic leukemia (CLL). Nonetheless, the precise mechanism of how miR-155 regulates the cell cycle in leukemic cells remains the subject of extensive research.

We edited the CLL cell line MEC-1 by CRISPR/Cas9 to introduce a short deletion within the MIR155HG gene. To describe changes at the transcriptome and miRNome level in miR-155-deficient cells, we performed mRNA-seq/miRNA-seq and validated changes by qRT-PCR. Flow cytometry was used to measure cell cycle kinetics. A WST-1 assay, hemocytometer, and Annexin V/PI staining assessed cell viability and proliferation.

The limited but phenotypically robust miR-155 modification impaired cell proliferation, cell cycle, and cell ploidy. This was accompanied by overexpression of the negative cell cycle regulator p21/CDKN1A and Cyclin D1 (CCND1). We confirmed the overexpression of canonical miR-155 targets such as PU.1, FOS, SHIP-1, TP53INP1 and revealed new potential targets (FCRL5, ISG15, and MX1).

We demonstrate that miR-155 deficiency impairs cell proliferation, cell cycle, transcriptome, and miRNome via deregulation of the MIR155HG/TP53INP1/CDKN1A/CCND1 axis. Our CLL model is valuable for further studies to manipulate miRNA levels to revert highly aggressive leukemic cells to nearly benign or non-leukemic types.

Hypoxia-inducible factor-1α (HIF-1α), a master regulator of cellular adaptation to hypoxia, drives colorectal cancer (CRC) progression by fueling angiogenesis, metastasis, and therapy resistance. Emerging evidence delineates intricate crosstalk between non-coding RNAs (ncRNAs)-including microRNAs, long non-coding RNAs, and circular RNAs-and HIF-1α, forming bidirectional regulatory networks that orchestrate CRC pathogenesis. By interacting with HIF-1α, these non-coding RNAs contribute to the orchestration of the aggressive hypoxic tumor microenvironment. Recent studies have evaluated the clinical potential of lncRNAs and miRNAs in the realms of non-invasive liquid biopsies and RNA-targeted therapies. This review offers a comprehensive synthesis of recent investigations into the mechanisms by which lncRNAs and miRNAs interact with HIF-1α to modulate CRC progression. Additionally, we further explore the clinical implications of ncRNA/HIF-1α crosstalk, emphasizing their potential as diagnostic biomarkers and therapeutic targets, while also spotlighting intriguing and promising areas of ncRNA research. Methods: In this study, our search strategy employed in databases such as PubMed, Web of Science, and EMBASE is as follows: we will specify search terms, including combinations of "non-coding RNA", "HIF-1α", and "colorectal cancer", along with a date range for the literature search (for example, from 2000 to 2025) to capture the most relevant and up-to-date research.

Ovarian and cervical cancers are the two most frequent kind of gynaecological cancers (GCs). In spite of advances in prevention, screening and treatment, cervical cancer still leads to an increased morbidity and mortality worldwide. Ovarian cancer is often detected at a late stage, which significantly reduces the effectiveness of available treatments. Therefore, novel methods are desperately needed to improve the clinical care of GC patients. MicroRNAs, also known as short noncoding RNAs (miRNAs/miRs), are a diverse group of RNAs with a length of 22 nucleotides. These typically cause translational repression and mRNA degradation by interacting with target mRNAs' 3' untranslated region (3'-UTR), together with other regions and gene promoters. Under certain conditions, they are also able to activate translation or regulate transcription. It has been demonstrated that miRNAs are crucial to several biological processes leading to tumorigenesis, including GCs. Recent research has shown that miR-9 affects carcinogenesis. In this review, we will provide an overview of current research on the potential utility of miR-9 in the diagnosis, prognosis, and therapy of ovarian and cervical malignancies.

Cancer is a rising issue worldwide, and numerous studies have focused on understanding the underlying reasons for its occurrence and finding proper ways to defeat it. By applying technological advances, researchers are continuously uncovering and updating treatments in cancer therapy. Their vast functions in the regulation of cell growth and proliferation and their significant role in the progression of diseases, including cancer. This review provides a comprehensive analysis of ncRNAs in breast cancer, focusing on long non-coding RNAs such as HOTAIR, MALAT1, and NEAT1, as well as microRNAs such as miR-21, miR-221/222, and miR-155. These ncRNAs are pivotal in regulating cell proliferation, metastasis, drug resistance, and apoptosis. Additionally, we discuss experimental approaches that are useful for studying them and highlight the advantages and challenges of each method. We then explain the results of these clinical trials and offer insights for future studies by discussing major existing gaps. On the basis of an extensive number of studies, this review provides valuable insights into the potential of ncRNAs in cancer therapy. Key findings show that even though the functions of ncRNAs are vast and undeniable in cancer, there are still complications associated with their therapeutic use. Moreover, there is an absence of sufficient experiments regarding their application in mouse models, which is an area to work on. By emphasizing the crucial role of ncRNAs, this review underscores the need for innovative approaches and further studies to explore their potential in cancer therapy.

The B cell lymphoma 2 (BCL2) protein family critically controls apoptosis by regulating the release of cytochrome c from mitochondria. In this cutting-edge review, we summarize the basic biology regulating the BCL2 family including canonical and non-canonical functions, and highlight milestones from basic research to clinical applications in cancer and other pathophysiological conditions. We review laboratory and clinical development of BH3-mimetics as well as more recent approaches including proteolysis targeting chimeras (PROTACs), antibody-drug conjugates (ADCs) and tools targeting the BH4 domain of BCL2. The first BCL2-selective BH3-mimetic, venetoclax, showed remarkable efficacy with manageable toxicities and has transformed the treatment of several hematologic malignancies. Following its success, several chemically similar BCL2 inhibitors such as sonrotoclax and lisaftoclax are currently under clinical evaluation, alone and in combination. Genetic analysis highlights the importance of BCL-XL and MCL1 across different cancer types and the possible utility of BH3-mimetics targeting these proteins. However, the development of BH3-mimetics targeting BCL-XL or MCL1 has been more challenging, with on-target toxicities including thrombocytopenia for BCL-XL and cardiac toxicities for MCL1 inhibitors precluding clinical development. Tumor-specific BCL-XL or MCL1 inhibition may be achieved by novel targeting approaches using PROTACs or selective drug delivery strategies and would be transformational in many subtypes of malignancy. Taken together, we envision that the targeting of BCL2 proteins, while already a success story of translational research, may in the foreseeable future have broader clinical applicability and improve the treatment of multiple diseases.

(1) Background: Glioblastoma (GBM) is one of the most aggressive brain tumors with a poor prognosis. Therefore, new insights into GBM diagnosis and treatment are required. In addition to differentially expressed mRNAs, miRNAs may have the potential to be applied as diagnostic biomarkers. (2) Methods: In this study, profiling of human miRNAs in combination with mRNAs was performed on total RNA isolated from tissue samples of five control and five GBM patients, using a high-throughput RNA sequencing (RNA-Seq) approach. (3) Results: A total of 35 miRNAs and 365 mRNAs were upregulated, while 82 miRNAs and 1225 mRNAs showed significant downregulation between tissue samples of GBM patients compared to the control samples using the iDEP tool to analyze RNA-Seq data. To validate our results, the expression of five miRNAs (hsa-miR-196a-5p, hsa-miR-21-3p, hsa-miR-10b-3p, hsa-miR-383-5p, and hsa-miR-490-3p) and fourteen mRNAs (E2F2, HOXD13, VEGFA, CDC45, AURKB, HOXC10, MYBL2, FABP6, PRLHR, NEUROD6, CBLN1, HRH3, HCN1, and RELN) was determined by RT-qPCR assay. The miRNet tool was used to build miRNA-target interaction. Furthermore, a protein-protein interaction (PPI) network was created from the miRNA targets by applying the NetworkAnalyst 3.0 tool. Based on the PPI network, a functional enrichment analysis of the target proteins was also carried out. (4) Conclusions: We identified an miRNA panel and several deregulated mRNAs that could play an important role in tumor development and distinguish GBM patients from healthy controls with high sensitivity and specificity using total RNA isolated from tissue samples.

Glioblastoma multiforme (GBM) is the most common brain tumor and one of the most aggressive, with a median overall survival (OS) of only 15-18 months. These characteristics make it necessary to identify new targets for the improvement of prognosis and better prediction of response to therapies currently available for GBM patients. One possible candidate target could be the evaluation of miRNAs. miRNAs are small non-coding RNAs that play important roles in post-transcriptional gene regulation. Due to their functions, miRNAs also control biological processes underlying the development of GBM and may be considered possible targets with a clinical role. This narrative review introduces the concept of miRNAs in GBM from a clinical and a molecular perspective and then addresses the specific miRNAs that are most described in the literature as relevant for the development, the prognosis, and the response to therapies for patients affected by GBM.

Cancer metastasis is a complicated biological process that critically affects cancer progression, patient outcomes, and treatment plans. A significant step in metastasis is the formation of a pre-metastatic niche (PMN). A small subset of cells within tumors, known as cancer stem cells (CSCs), possess unique characteristics including, differentiation into different cell types within the tumor, self-renewal, and resistance to conventional therapies, that enable them to initiate tumors and drive metastasis. PMN plays an important role in preparing secondary organs for the arrival and proliferation of CSCs, thereby facilitating metastasis. CSC-derived exosomes are crucial components in the complex interplay between CSCs and the tumor microenvironment. These exosomes function as transporters of various substances that can promote cancer progression, metastasis, and modulation of pre-metastatic environments by delivering microRNA (miRNA, miR) cargo. This review aims to illustrate how exosomal miRNAs (exo-miRs) secreted by CSCs can predispose PMN and promote angiogenesis and metastasis.

In an obesogenic environment, such as the one we have been experiencing in recent decades, epigenetics provides answers to the relationship between hereditary and environmentally acquired patterns that have significantly contributed to the global rise in obesity prevalence. MicroRNA (miRNA) constitutes a diminutive non-coding small RNA molecule, 20 to 24 nucleotides in length, that functions as a regulator of gene regulation at the post-translational level. Circulating miRNAs (c-miRNAs) have been detected in multiple body fluids, including blood, plasma, serum, saliva, milk from breastfeeding mothers, and urine. These molecules hold significant therapeutic value and serve as extracellular biomarkers in metabolic diseases. They aid in the diagnosis and tracking of therapy responses, as well as dietary and physical habit modifications. Researchers have studied c-miRNAs as potential biomarkers for diagnosing and characterizing systemic diseases in people of all ages and backgrounds since then. These conditions encompass dyslipidemia, type 2 diabetes mellitus (T2DM), cardiovascular risk, metabolic syndrome, cardiovascular diseases, and obesity. This review therefore analyzes the usefulness of c-miRNAs as therapeutic markers over the past decades. It also provides an update on c-miRNAs associated with general obesity and overweight, as well as with the most prevalent pathologies in the adult population. It also examines the effect of different nutritional approaches and physical activity regarding the activity of miRNAs in circulation in adults with overweight or general obesity. All of this is done with the aim of evaluating their potential use as biomarkers in various research contexts related to overweight and obesity in adults.

Cancer, characterized by the uncontrolled proliferation of cells, is one of the leading causes of death globally, with approximately one in five people developing the disease in their lifetime. While many driver genes were identified decades ago, and most cancers can be classified based on morphology and progression, there is still a significant gap in knowledge about genetic aberrations and nuclear DNA damage. The study of two critical groups of genes-tumor suppressors, which inhibit proliferation and promote apoptosis, and oncogenes, which regulate proliferation and survival-can help to understand the genomic causes behind tumorigenesis, leading to more personalized approaches to diagnosis and treatment. Aberration of tumor suppressors, which undergo two-hit and loss-of-function mutations, and oncogenes, activated forms of proto-oncogenes that experience one-hit and gain-of-function mutations, are responsible for the dysregulation of key signaling pathways that regulate cell division, such as p53, Rb, Ras/Raf/ERK/MAPK, PI3K/AKT, and Wnt/β-catenin. Modern breakthroughs in genomics research, like next-generation sequencing, have provided efficient strategies for mapping unique genomic changes that contribute to tumor heterogeneity. Novel therapeutic approaches have enabled personalized medicine, helping address genetic variability in tumor suppressors and oncogenes. This comprehensive review examines the molecular mechanisms behind tumor-suppressor genes and oncogenes, the key signaling pathways they regulate, epigenetic modifications, tumor heterogeneity, and the drug resistance mechanisms that drive carcinogenesis. Moreover, the review explores the clinical application of sequencing techniques, multiomics, diagnostic procedures, pharmacogenomics, and personalized treatment and prevention options, discussing future directions for emerging technologies.

Extracellular vesicles (EVs) are nanovesicles that facilitate intercellular communication by carrying essential biomolecules under physiological and pathological conditions including microRNAs (miRNAs). They are found in various body fluids, such as blood, urine, and saliva, and their levels fluctuate with disease progression, making them valuable diagnostic tools. However, isolating EVs is challenging due to their small size and biological complexity. Here, we summarize the principles behind the most common EV isolation methods including ultracentrifugation, precipitation, immunoaffinity, sorting, ultrafiltration, size exclusion chromatography, and microfluidics while highlighting protocol strengths and weaknesses. We also review the main strategies to identify and quantify circulating miRNAs with a particular focus on EV-encapsulated miRNAs. Since these miRNAs hold special clinical interest derived from their superior stability and therapeutic potential, the information provided here should provide valuable guidance for future research initiatives in the promising field of disease diagnostic and treatment based on EV-encapsulated miRNAs.

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.

Understanding the mechanisms underlying endometrial cancer progression is crucial for the development of effective targeted therapies. In this study, we investigated the role of MTFR2 in endometrial cancer cell.

The expression of MTFR2 in endometrial cancer was analyzed using The Cancer Genome Atlas (TCGA) dataset and detected in endometrial cancer tissues and cells, respectively. Gain-of-function and loss-of-function approaches were utilized to investigate the impact of MTFR2 on endometrial cancer cell proliferation and tumorigenesis in both in vitro and in vivo settings. Computational tools were employed to predict microRNAs (miRNAs) that potentially regulate MTFR2, and these predictions were experimentally validated.

The expression of MTFR2 is enhanced in endometrial carcinoma, and it is positively correlated with the poor prognosis of patients. Functional studies show that MTFR2 promoted the proliferation, migration and invasion of endometrial cancer cells. Bioinformatics analysis and luciferase assays identified that MTFR2 is a potential target of miR-132-3p, and transfection with miR-132-3p mimics attenuated the MTFR2-induced activation of the PI3K/Akt pathway.

Our findings highlight the critical role of MTFR2 in promoting endometrial cancer cell proliferation and growth through the miR-132-3p/PI3K/Akt signaling pathway. Targeting this signaling axis may offer potential therapeutic strategies for endometrial cancer treatment.

Nucleic-acid-based therapies have emerged as a pivotal domain within contemporary biomedical science, marked by significant advancements in recent years. These innovative treatments primarily operate through the precise binding of DNA or RNA molecules to discrete target genes, subsequently suppressing the expression of the target proteins. The spectrum of nucleic-acid-based therapies encompasses antisense oligonucleotides (ASOs), small interfering RNAs (siRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs), etc. Compared to more traditional medicinal approaches, nucleic-acid-based therapies stand out for their highly targeted action on specific genes, as well as their potential for chemical modification to improve resistance to nucleases, ensuring sustained therapeutic activity and mitigating immunogenicity concerns. Nevertheless, these molecules' limited cellular permeability necessitates the deployment of delivery vectors to enhance their intracellular uptake and stability. As nucleic-acid-based therapies progressively display promising pharmacodynamic profiles, there has been a burgeoning interest in these treatments for applications in clinical research. This review aims to summarize the variety of nucleic acid drugs and their mechanisms, evaluate the present status in research and application, discourse on prospective trends, and potential challenges ahead. These innovative therapeutics are anticipated to assume a pivotal role in the management of a wide array of diseases.

MiR-136 is abnormally expressed in many types of metastatic tumors and is closely associated with tumor cell proliferation, apoptosis, invasion, and metastasis, indicating its important role in tumor development and progression. This review summarizes current knowledge regarding miR-136's molecular mechanisms, functional roles, and impact on chemotherapy in different human cancers.

A literature search was conducted in PubMed and Web of Science using "miR-136" and "metastatic tumors" as English keywords, and in CNKI and Wanfang databases using the same terms in Chinese. Studies related to miR-136 research in metastatic tumors and high-quality evidence from similar studies were included. Meta-analyses, dissertations, conference papers, low-quality articles, unavailable full-text articles, and republished articles were excluded.

This review synthesizes the current understanding of miR-136's role in various cancers, including osteosarcoma, gastric cancer, gallbladder cancer, esophageal cancer, prostate cancer, colorectal cancer, breast cancer, glioma, and thyroid cancer. miR-136 acts as a tumor suppressor by targeting various genes, including MTDH, PTEN, MAP2K4, MUC1, LRH-1, MIEN1, RASAL2, CYR61, and KLF7. It influences multiple signaling pathways, including the ERK/mitogen-activated protein kinase, Wnt/β-catenin, Ha-Ras, PI3K/Akt, Aurora-A kinase, nuclear factor-κB, and JNK pathways. Furthermore, miR-136 is involved in chemoresistance by modulating ROCK1, PPP2R2A, and the miR-136-Notch3 signaling axis.

MiR-136 demonstrates promising potential as a novel biomarker and therapeutic target in various human cancers. Further research is needed to fully elucidate its complex roles in cancer development, progression, and drug resistance, particularly regarding its potential in immunotherapy.

Chronic lymphocytic leukemia (CLL) is the most frequent type of leukemia. It typically occurs in older patients and has a highly variable clinical course. Leukemic transformation is initiated by specific genomic alterations that interfere with the regulation of proliferation and apoptosis in clonal B-cells.

The diagnosis is established by blood counts, blood smears, and immunophenotyping of circulating B-lymphocytes, which identify a clonal B-cell population carrying the CD5 antigen as well as typical B-cell markers.

Two clinical staging systems, Rai and Binet, provide prognostic information by using the results of physical examination and blood counts. Various biological and genetic markers provide additional prognostic information. Deletions of the short arm of chromosome 17 (del(17p)) and/or mutations of the TP53 gene predict a shorter time to progression with most targeted therapies. The CLL international prognostic index (CLL-IPI) integrates genetic, biological, and clinical variables to identify distinct risk groups of patients with CLL. The CLL-IPI retains its significance in the era of targeted agents, but the overall prognosis of CLL patients with high-risk stages has improved.

Only patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. When treatment is indicated, several therapeutic options exist: combinations of the BCL2 inhibitor venetoclax with obinutuzumab, or venetoclax with ibrutinib, or monotherapy with one of the inhibitors of Bruton tyrosine kinase (BTK). At relapse, the initial treatment may be repeated if the treatment-free interval exceeds 3 years. If the leukemia relapses earlier, therapy should be changed using an alternative regimen.

Combinations of targeted agents now provide efficient therapies with a fixed duration that generate deep and durable remissions. These fixed-duration therapies have gained territory in the management of CLL, as they are cost-effective, avoid the emergence of resistance, and offer treatment free time to the patient. The cure rate of these novel combination regimens is unknown. Moreover, the optimal sequencing of targeted therapies remains to be determined. A medical challenge is to treat patients who are double-refractory to both BTK and BCL2 inhibitors. These patients need to be treated within experimental protocols using novel drugs.

Given the importance of epigenetic mechanisms in the downregulation of tumor suppressor genes and the activation of oncogenes, herein we focused on microRNA silencing as a cause of oncogene activation in laryngeal squamous cell carcinoma (LSCC). In our study, we aimed at identifying regulatory microRNA signatures in LSCC mRNA profiles from our previous analysis. By this approach, we identified 14 overexpressed genes that shared a common regulatory hsa-miR-299-5p signature in LSCC samples. Subsequent RT-qPCR analysis confirmed the downregulation of hsa-miR-299-5p as well as the overexpression of 3 out of 14 genes: PATZ1, PURB, and TFAM in both LSCC cell lines and tumor samples compared to non-cancerous controls. Further, we have demonstrated a direct interaction between hsa-miR-299-5p and TFAM 3'UTR using dual luciferase assay. Importantly, we have shown decreased TFAM protein level after mimicry of hsa-miR-299-5p expression in three LSCC cell lines. Moreover, cell lines with restored activity of hsa-miR-299-5p demonstrated reduced viability compared to cell lines treated with the negative control. In conclusion, we point to hsa-miR-299-5p as a tumor-suppressive microRNA with the potential to regulate TFAM and consequently influence cell viability.

A large fraction of the human genome is transcribed in RNA molecules that do not encode for proteins but that do have a crucial role in regulating almost every level of gene expression and, thus, define the specific phenotype of each cell. These non-coding RNAs include well-characterized microRNAs and thousands of less-defined longer transcripts, named long non-coding RNAs. Both types markedly affect the onset and the progression of numerous pathologies, ranging from cancer to vascular and neuro-degenerative diseases. In recent years, a substantial effort has been made to design drugs targeting ncRNAs, and promising advancements have been produced from micro-RNA mimics and inhibitors. Each ncRNA controls several targets, and the overall effect of its inhibition or overexpression depends on the function of the set of genes it regulates. Therefore, in selecting the most appropriate target, and predicting the final outcome of ncRNA-based therapies, it is crucial to have and utilize detailed and accurate knowledge of their functional interactions. In this review, I recapitulate the principal resources which collect information on microRNA and lncRNA networks, focusing on the non-homogeneity of the data that result from disparate approaches. I highlight the role of RNA identifiers and interaction evidence standardization in helping the user to filter and integrate data derived from different databases in a reliable functional web of regulative relations.

Tumoral calcinosis (TC) is an extremely rare inherited disease characterized by multilobulated, dense ectopic calcified masses, usually in the periarticular soft tissue regions. In a previous study, we isolated a primary cell line from an ectopic lesion of a TC patient carrying a previously undescribed GALNT3 mutation. Here, we researched whether a stem cell (SC) subpopulation, which may play a critical role in TC progression, could be present within these lesions.

A putative SC subpopulation was initially isolated by the sphere assay (marked as TC1-SC line) and characterized for its stem-like phenotype through several cellular and molecular assays, including colony forming unit assay, immunofluorescence staining for mesenchymal SC (MSC) markers, gene expression analyses for embryonic SC (ESC) marker genes, and multidifferentiation capacity. In addition, a preliminary expression pattern of osteogenesis-related pathways miRNAs and genes were assessed in the TC1-SC by quantitative Real-Time PCR (qPCR).

These cells were capable of differentiating into both the adipogenic and the osteogenic lineages. Moreover, they showed the presence of the MSC and ESC markers, confirmed respectively by using immunofluorescence and qualitative reverse transcriptase PCR (RT-PCR), and a good rate of clonogenic capacity. Finally, qPCR data revealed a signature of miRNAs (i.e., miR-21, miR-23a-3p, miR-26a, miR-27a-3p, miR-27b-3p, and miR-29b-3p) and osteogenic marker genes (i.e., ALP, RUNX2, COLIA1, OPG, OCN, and CCN2) characteristic for the established TC1-SC line.

The establishment of this in vitro cell model system could advance the understanding of mechanisms underlying TC pathogenesis, thereby paving the way for the discovery of new diagnostic and novel gene-targeted therapeutic approaches for TC.

Background: Liquid biopsy has gained significant attention as a non-invasive method for cancer detection and monitoring. IsomiRs and tRNA-derived fragments (tRFs) are small non-coding RNAs that arise from non-canonical microRNA (miRNAs) processing and the cleavage of tRNAs, respectively. These small non-coding RNAs have emerged as pro-mising cancer biomarkers, and their distinct expression patterns highlight the need for further exploration of their roles in cancer research. Methods: In this study, we investigated the differential expression profiles of miRNAs, isomiRs, and tRFs in plasma extracellular vesicles (EVs) from colorectal and prostate cancer patients compared to healthy controls. Subsequently, a combinatorial analysis using the CombiROC package was performed to identify a panel of biomarkers with optimal diagnostic accuracy. Results: Our results demonstrate that a combination of miRNAs, isomiRs, and tRFs can effectively di- stinguish cancer patients from healthy controls, achieving accuracy and an area under the curve (AUC) of approximately 80%. Conclusions: These findings highlight the potential of a combinatorial approach to small RNA analysis in liquid biopsies for improved cancer diagnosis and management.

Lung cancer is one of the deadliest malignancies worldwide, with distant metastasis being a major cause of death. However, the specific mechanisms of lung cancer metastasis remain unclear. NcRNAs, a widely present type of non-coding RNAs in the body, constitute about 98% of the human genome, lacking protein-coding capacity but involved in various cellular processes such as proliferation, apoptosis, invasion, and migration. Studies have shown that ncRNAs play a crucial role in the metastasis of lung cancer, although research in this area is limited. This review summarizes the biological origins and functions of ncRNAs, their specific roles and mechanisms in lung cancer metastasis, and discusses their potential for early screening and therapeutic applications in lung cancer. Furthermore, it outlines the challenges in translating basic advancements of ncRNAs in lung cancer metastasis into clinical practice.

Single-cell sequencing-based techniques are revolutionizing all fields of biomedical sciences, including normal kidney development and how this is disturbed in the development of Wilms tumor. The many different techniques and the differences between them can obscure which technique is best used to answer which question. In this review we summarize the techniques currently available, discuss which have been used in kidney development or Wilms tumor context, and which techniques can or should be combined to maximize the increase in biological understanding we can get from them.

Recent advancements in microRNAs (miRNAs) research have revealed their key roles in both normal physiological processes and pathological conditions, leading to potential applications in diagnostics and therapeutics. However, the path forward is fraught with several scientific and technical challenges. This review article briefly explores the milestones of the discovery, biogenesis, functions, and application for clinical diagnostic and therapeutic strategies of miRNAs. The potential challenges and future directions are also discussed to fully harness their capabilities.

Colorectal cancer (CRC), the third most commonly diagnosed and second most lethal cancer worldwide, necessitates efficient early detection strategies to improve patient outcomes. This review evaluates the promise of novel blood-based biomarkers for early detection of CRC.

A systematic review, registered with PROSPERO (CRD42024513770) and adhering to PRISMA guidelines, was conducted across multiple databases from January 1st, 2020 to December 31st, 2022. The comprehensive search strategy centered on sensitivity, specificity, and AUC-ROC of multiple types of molecular blood biomarkers.

Of total of 142 included articles, 59 were on protein, 58 on RNA, and 21 on DNA. The investigation into DNA biomarkers revealed that cfDNA and ctDNA carry significant potential for early CRC diagnosis. For instance, methylation patterns in genes such as MYO1-G and NDRG4 exhibited high diagnostic accuracies with AUCs reaching up to 0.996. RNA biomarkers like miRNAs and circRNAs also showed promising results, with circ_0011536 achieving AUCs of 0.982. Protein biomarkers, contrasted with established cancer markers, unveiled notable candidates like Irisin and ANXA2, with AUCs surpassing 0.96. The review highlights several individual markers and panels with the potential to improve upon existing CRC screening tests.

Despite the promise shown by the novel biomarkers, challenges persist, including small sample sizes, potential selection biases, and a lack of comprehensive cost-effectiveness analysis. Future research should focus on large-scale, multicenter, prospective studies across diverse populations. The findings advocate for an integrated biomarker approach, potentially revolutionizing CRC screening and aligning it with clinical realities through rigorous validation.

Glioblastoma (GBM) is the most common malignant primary brain cancer with poor prognosis due to the resistant to current treatments, including the first-line drug temozolomide (TMZ). Accordingly, it is urgent to clarify the mechanism of chemotherapeutic resistance to improve the survival rate of patients. In the present study, by integrating comprehensive non-coding RNA-seq data from multiple cohorts of GBM patients, we identified that a series of miRNAs are frequently downregulated in GBM patients compared with the control samples. Among them, a high level of miR-124 is closely associated with a favorable survival rate in the clinical patients. In the phenotype experiment, we demonstrated that miR-124 overexpression increases responsiveness of GBM cells to TMZ-induced cell death, and vice versa. In the mechanistic study, we for the first time identified that RAD51, a key functional molecule in DNA damage repair, is a novel and bona fide target of miR-124 in GBM cells. Given that other miR-124-regulated mechanisms on TMZ sensitivity have been reported, we performed recue experiment to demonstrate that RAD51 is essential for miR-124-mediated sensitivity to TMZ in GBM cells. More importantly, our in vivo functional experiment showed that combinational utilization of miR-124 overexpression and TMZ presents a synergetic therapeutic benefit in the orthotopic GBM mice model. Taken together, we rationally explained a novel and important mechanism of the miR-124-mediated high sensitivity to TMZ-induced cell death in GBM and provided evidence to support that miR-124-RAD51 regulatory axis could be a promising candidate in the comprehensive treatment with TMZ in GBM.