Cancer, influenced by genetics and the environment, involves anoikis, a cell death mechanism upon extracellular matrix detachment crucial for metastasis. Understanding this relationship is key for therapy. We analyze cancer and anoikis trends using bibliometrics.

A search was conducted from Web of Science Core, PubMed, Scopus and non-English databases such as the CNKI (inception- 21 December 2024). Data analysis employed Microsoft Excel, VOSviewer, CiteSpace, R software, and the online platform (https://bibliometric.com/).

2510 publications were retrieved, with a significant increase in the last decade. China led, the University of Texas system was productive, and the Oncogene Journal was popular. Breast, and colorectal cancers were frequently studied. Among them, representative tumor-related mechanisms were identified, commonalities such as (EMT, ECM, autophagy) and respective specific mechanisms were summarized.

This bibliometric analysis highlights rapid advances in anoikis research in cancer, emphasizing EMT and FAK pathways' translational potential, guiding targeted therapies, and improving cancer treatment outcomes.

Epithelial-mesenchymal transition (EMT) is a key phenotypic switch in cancer metastasis, leading to fatal consequences for patients. Under geometric constraints, the morphology of cancer cells changes in both cellular and subcellular levels, whose effects on EMT are, however, not fully understood. Herein, we designed and fabricated chimeric micropatterns of polystyrene (PS) with adhesion contrast to reveal the impacts of cell shapes and nuclear shapes on EMT in a decoupled way. Cell elongation was modulated via microwell aspect ratios (ARs), and nuclear deformation was generated through a micropillar array in the microwell. Human non-small cell lung cancer cells (A549) were cultured on the quasi-three dimensional micropatterned surfaces, and transforming growth factor-β1 (TGF-β1) was added to induce EMT. We found that chimeric micropatterns upregulated EMT with an increase of cellular AR and nuclear indentation under given TGF-β1. The subsequent assessment of the contractility and oriented assembly of microfilaments elucidated the key role of mechanotransduction in cell elongation and EMT, as proved by myosin inhibition, while it was obstructed by micropillars in the chimeric micropattern. Hence, the micropillar array possessed a nonmonotonic influence, enhancing the EMT of cells with AR of 1, but hindering the EMT with an impact more significant on microwells with large ARs due to the impeded cytoskeleton assembly. This fundamental research has illustrated the complex of cellular and subcellular geometries on cell behaviors including phenotype transition in cancer metastasis.

Endometrial receptivity is vital for the successful implantation of embryos in sheep. Insufficient receptivity is a major cause of implantation failure, highlighting the need to understand the underlying mechanisms. MicroRNAs (miRNAs) play an essential role in the epigenetic regulation of endometrial receptivity and embryo implantation by influencing post-transcriptional processes. However, the specific mechanisms by which various miRNAs contribute to endometrial receptivity and embryo implantation in sheep remain to be fully elucidated. Our research highlights the significant role of oar-miR-29a, which promotes the migration and proliferation of sheep endometrial epithelial cells (sEECs). We found that oar-miR-29a enhances mRNA expression associated with proliferation, migration, and epithelial-mesenchymal transition (EMT) in sEECs. Additionally, this miRNA enhances the proliferation and migration capabilities of sheep trophoblast cells (sTCs). Moreover, our findings suggest that the target genes of oar-miR-29a are involved in key biological processes and pathways essential for embryo implantation. Notably, our analysis identifies cell division cycle 42 (CDC42) as a target gene of oar-miR-29a. In summary, oar-miR-29a plays a crucial role in promoting endometrial receptivity by targeting CDC42 in sheep. These findings provide insights into the miRNA-based regulatory mechanisms governing uterine physiology during the early stages of pregnancy, emphasizing the importance of this research for improving reproductive outcomes in sheep.

Introduction: Cannabis sativa extract has been used as an herbal medicine since ancient times. It is one of the most researched extracts, especially among supportive treatments against cancer. Prostate cancer is one of the most frequently diagnosed cancer types in men worldwide and an estimated 288,300 new cases were diagnosed in 2023. Today, many advanced therapeutic approaches are used for prostate cancer, such as immunotherapy and chemotherapy, but acquired drug resistance, long-term drug usage and differentiation of cancer cells mostly restricted the efficiency of therapies. Therefore, it is thought that the use of natural products to overcome these limitations and improve the effectiveness of existing therapies may offer promising approaches. The present study focused on the investigation of the possible enhancer role of cannabidiol (CBD), which is a potent ingredient compound of Cannabis, on the chemotherapeutic agent etoposide in prostate cancer cells. Methods: Herein, we tested the potentiator role of CBD on etoposide in prostate cancer cells by testing the cytotoxic effect, morphological alterations, apoptotic effects, autophagy, unfolded protein response (UPR) signaling, endoplasmic reticulum-associated degradation mechanism (ERAD), angiogenic and androgenic factors, and epithelial-mesenchymal transition (EMT). In addition, we examined the combined treatment of CBD and etoposide on colonial growth, migrative, invasive capability, 3D tumor formation, and cellular senescence. Results: Our findings demonstrated that cotreatment of etoposide with CBD importantly suppressed autophagic flux and induced ERAD and UPR signaling in LNCaP cells. Also, CBD strongly enhanced the etoposide-mediated suppression of androgenic signaling, angiogenic factor VEGF-A, protooncogene c-Myc, EMT, and also induced apoptosis through activation caspase-3 and PARP-1. Moreover, coadministration markedly decreased tumorigenic properties, such as proliferative capacity, colonial growth, migration, and 3D tumor formation and also induced senescence. Altogether, our data revealed that CBD has a potent enhancer effect on etoposide-associated anticancer activities. Conclusion: The present study suggests that the use of CBD as a supportive therapy in existing chemotherapeutic approaches may be a promising option, but this effectiveness needs to be investigated on a large scale.

How activity affects the glassy dynamics is crucial for several biological processes. Furthermore, active glasses offer fascinating phenomenologies, extend the scope of equilibrium glass-forming liquids, and can provide novel insights into the original problem. We introduce a family of novel approaches to investigating the relaxation dynamics of active glasses via an active elastoplastic model (EPM). These approaches describe the relaxation dynamics via local plastic yielding and can provide improved insights as we can study various aspects of the system separately. Activity enters the model via three crucial features: activity-mediated plastic yielding, activated barrier crossing, and persistent rotational dynamics of the yielding direction. We first consider a minimal active EPM that adds the effect of active yielding to a thermal EPM. We show that this active EPM captures the known results of active glasses within a reasonable parameter space. The results also agree well with the analytical results for active glasses when activity is small. The minimal model breaks down at very low temperatures where other effects become important. Looking at the broader model class, we demonstrate that whereas active yielding primarily dominates the relaxation dynamics, the persistence of the yielding direction governs the dynamic heterogeneity in active glasses.

In the domain of addressing cancer resistance, challenges such as limited effectiveness and treatment resistance remain persistent. Hypoxia is a key feature of solid tumors and is strongly associated with poor prognosis in cancer patients. Another significant portion of the development of acquired drug resistance is attributed to tumor stemness. Cancer stem cells (CSCs), a small tumor cell subset with self-renewal and proliferative abilities, are crucial for tumor initiation, metastasis, and intra-tumoral heterogeneity. Studies have shown a significant association between hypoxia and CSCs in the context of tumor resistance. Recent studies reveal a strong link between hypoxia and tumor stemness, which together promote tumor survival and progression during treatment. This review elucidates the interplay between hypoxia and CSCs, as well as their correlation with resistance to therapeutic drugs. Targeting pivotal genes associated with hypoxia and stemness holds promise for the development of novel therapeutics to combat tumor resistance.

Pancreatic ductal adenocarcinoma (PDAC) is the most common and aggressive type of pancreatic cancer, with a five-year survival rate below 8%. Its high mortality is largely due to late diagnosis, metastatic potential, and resistance to therapy. Epithelial-mesenchymal transition (EMT) plays a key role in metastasis, enabling cancer cells to become mobile. Partial EMT, where cells maintain both epithelial and mesenchymal traits, is more frequent in tumors than complete EMT and contributes to cancer progression. The long non-coding RNA MIR31 host gene (MIR31HG) has recently emerged as a critical factor in PDAC oncogenesis. This study aimed to investigate MIR31HG's role in partial EMT and its association with the basal-like PDAC subtype.

We analyzed the relationship between MIR31HG expression, partial EMT, and the basal-like subtype of PDAC by integrating data from public databases. We reanalyzed public data from PDAC patient-derived organoids to assess MIR31HG expression and gene signatures under hypoxic and normoxic conditions. RNA sequencing and bioinformatics analyses, including gene set enrichment analysis (GSEA), were used to investigate differentially expressed genes and pathway enrichments. EMT, partial EMT, and hypoxia scores were calculated based on the expression levels of specific gene sets.

We observed that MIR31HG overexpression strongly correlates with higher partial EMT scores and the stabilization of the epithelial phenotype in PDAC. MIR31HG is highly expressed in the basal-like subtype of PDAC, which exhibits partial EMT traits. Hypoxia, a hallmark of basal-like PDAC, was shown to significantly induce MIR31HG expression, thereby promoting the basal-like phenotype and partial EMT. In patient-derived organoids, hypoxic conditions increased MIR31HG expression and enhanced basal-like and partial EMT gene signatures, while normoxia reduced these expressions. These findings suggest that hypoxia-induced MIR31HG expression plays a crucial role in driving the aggressive basal-like subtype of PDAC.

Our results indicate that MIR31HG is crucial in regulating PDAC progression, particularly in the aggressive basal-like subtype associated with hypoxia and partial EMT. Targeting the MIR31HG-mediated network may offer a novel therapeutic approach to combat hypoxia-driven PDAC.

Epithelial-mesenchymal transition (EMT) is a cellular de-differentiation process that provides cells with the increased plasticity and stem cell-like traits required during embryonic development, tissue remodeling, wound healing and metastasis. Morphologically, EMT confers tumor cells with fibroblast-like properties that lead to the rearrangement of cytoskeleton (loss of stiffness) and decrease of membrane rigidity by incorporating high level of poly-unsaturated fatty acids (PUFA) in their phospholipid membrane. Although large amounts of PUFA in membrane reduces rigidity and offers capabilities for tumor cells with the unbridled ability to stretch, bend and twist in metastasis, these PUFA are highly susceptible to lipid peroxidation, which leads to the breakdown of membrane integrity and, ultimately results in ferroptosis. To escape the ferroptotic risk, EMT also triggers the rewiring of metabolic program, particularly in lipid metabolism, to enforce the epigenetic regulation of EMT and mitigate the potential damages from ferroptosis. Thus, the interplay among EMT, lipid metabolism, and ferroptosis highlights a new layer of intricated regulation in cancer biology and metastasis. Here we summarize the latest findings and discuss these mutual interactions. Finally, we provide perspectives of how these interplays contribute to cellular plasticity and ferroptosis resistance in metastatic tumor cells that can be explored for innovative therapeutic interventions.

Glioblastoma multiforme (GBM) is characterized by substantial heterogeneity and limited therapeutic options. As molecular approaches to central nervous system tumors have gained prominence, this study examined the roles of three genes, TWIST2, GATA3, and HES5, known to be involved in oncogenesis, developmental processes, and maintenance of cancer stem cell properties, which have not yet been extensively studied in GBM. This study is the first to present gene expression data for TWIST2, GATA3, and HES5 specifically within the context of GBM patient survival.

Gene expression data for TWIST2, GATA3, and HES5 were collected from GBM and normal brain tissues using datasets from The Cancer Genome Atlas via the Genomic Data Commons portal and the Genotype-Tissue Expression database. These data were rigorously analyzed using in silico methods.

All three genes were significantly more expressed in GBM tissues than in normal tissues. TWIST2 and GATA3 were linked to lower survival rates in GBM patients. Interestingly, higher HES5 levels were associated with better survival rates, suggesting a complex role that needs more investigation.

This study shows that TWIST2, GATA3, and HES5 could help predict outcomes in GBM patients. Our multigene model offers a better understanding of GBM and points to new treatment options, bringing hope for improved therapies and patient outcomes. This research advances our knowledge of GBM and highlights the potential of molecular diagnostics in oncology.

Breast cancer remains one of the leading causes of mortality worldwide. While advancements in chemotherapy, immunotherapy, radiotherapy, and targeted therapies have significantly improved breast cancer treatment, many patients are diagnosed at advanced stages, where tumor cells exhibit aggressive behavior and therapy resistance. Understanding the mechanisms driving breast cancer progression is therefore critical. Metastasis is a major factor that drastically reduces patient prognosis and survival, accounting for most breast cancer-related deaths. ZEB proteins have emerged as key regulators of cancer metastasis. Beyond their role in metastasis, ZEB proteins also influence drug resistance. This review focuses on the role of ZEB1 and ZEB2 in regulating breast cancer metastasis. These proteins interact with components of the tumor microenvironment (TME) to drive cancer progression and metastasis. Additionally, ZEB proteins regulate angiogenesis through interactions with VEGF. Targeting ZEB proteins offers potential therapeutic benefits, particularly for aggressive breast cancer subtypes such as triple-negative breast cancer (TNBC), which often show poor therapeutic response. ZEB proteins also influence the sensitivity of breast cancer cells to chemotherapy, making them promising targets for enhancing treatment efficacy. Given their upregulation in breast cancer, ZEB proteins can serve as valuable diagnostic and prognostic markers.

This study investigated the relationship between E-cadherin down-regulation and enhanced pERK1/2 signaling in cervical cancer, evaluated their combined prognostic impact, and explored potential therapeutic targets.

We analyzed 188 cervical cancer specimens and 300 normal cervical tissue samples using tissue microarray and immunohistochemistry. Small interfering RNA transfection and western blotting were used to study molecular interactions in cervical cancer cell lines.

We observed a significant inverse correlation between E-cadherin and pERK1/2 expression, as well as poor disease-free survival and overall survival. Additionally, molecular analysis indicated that E-cadherin silencing enhanced ERK signaling and promoted cancer cell proliferation.

The findings suggest that E-cadherin and pERK1/2 are crucial biomarkers for cervical cancer prognosis and their interaction provides a potential target for therapeutic interventions. Further studies are recommended to explore these pathways in the clinical setting.

Transitions between solid-like and fluid-like states in living tissues have been found in steps of embryonic development and in stages of disease progression. Our current understanding of these transitions has been guided by experimental and theoretical investigations focused on how motion becomes arrested with increased mechanical coupling between cells, typically as a function of packing density or cell cohesiveness. However, cells actively respond to externally applied forces by contracting after a time delay, so it is possible that at some packing densities or levels of cell cohesiveness, mechanical coupling stimulates cell motion instead of suppressing it. Here we report our findings that at low densities and within multiple ranges of cell cohesiveness, cell migration speeds increase with these measures of mechanical coupling. Our observations run counter to our intuition that cell motion will be suppressed by increasingly packing or sticking cells together and may provide new insight into biological processes involving motion in dense cell populations.

Although the number of breast cancer deaths has decreased, and there have been developments in targeted therapies and combination treatments for the management of metastatic illness, metastatic breast cancer is still the second most common cause of cancer-related deaths in U.S. women. Numerous phases and a vast number of proteins and signaling molecules are involved in the invasion-metastasis cascade. The tumor cells penetrate and enter the blood or lymphatic vessels, and travel to distant organs via the lymphatic or blood vessels. Tumor cells enter cell cycle arrest, adhere to capillary beds in the target organ, and then disseminate throughout the organ's parenchyma, proliferating and enhancing angiogenesis. Each of these processes is regulated by changes in the expression of different genes, in which lncRNAs play a role in this regulation. Transcripts that are longer than 200 nucleotides and do not translate into proteins are called RNAs. LncRNA molecules, whose function depends on their unique molecular structure, play significant roles in controlling the expression of genes at various epigenetic levels, transcription, and so on. LncRNAs have essential functions in regulating the expression of genes linked to cell development in healthy and pathological processes, specialization, programmed cell death, cell division, invasion, DNA damage, and spread to other parts of the body. A number of cancer types have been shown to exhibit aberrant expression of lncRNAs. In this review, we describe the general characteristics, potential molecular mechanisms and targeted therapy of lncRNAs and discuss the emerging functions of lncRNAs in breast cancer.

Epithelial cell adhesion molecule (EpCAM) fused to IgG, IgA and IgM Fc domains was expressed to create IgG, IgA and IgM-like structures as anti-cancer vaccines in Nicotiana tabacum. High-mannose glycan structures were generated by adding a C-terminal endoplasmic reticulum (ER) retention motif (KDEL) to the Fc domain (FcK) to produce EpCAM-Fc and EpCAM-FcK proteins in transgenic plants via Agrobacterium-mediated transformation. Cross-fertilization of EpCAM-Fc (FcK) transgenic plants with Joining chain (J-chain, J and JK) transgenic plants led to stable expression of large quaternary EpCAM-IgA Fc (EpCAM-A) and IgM-like (EpCAM-M) proteins. Immunoblotting, SDS-PAGE and ELISA analyses demonstrated that proteins with KDEL had higher expression levels and binding activity to anti-EpCAM IgGs. IgM showed the strongest binding among the fusion proteins, followed by IgA and IgG. Sera from BALB/c mice immunized with these vaccines produced anti-EpCAM IgGs. Flow cytometry indicated that the EpCAM-Fc fusion proteins significantly activated CD8+ cytotoxic T cells, CD4+ helper T cells and B cells, particularly with EpCAM-FcKP and EpCAM-FcP (FcKP) × JP (JKP). The induced anti-EpCAM IgGs captured human prostate cancer PC-3 and colorectal cancer SW620 cells. Sera from immunized mice inhibited cancer cell proliferation, migration and invasion; down-regulated proliferation markers (PCNA, Ki-67) and epithelial-mesenchymal transition markers (Vimentin); and up-regulated E-cadherin. These findings suggest that N. tabacum can produce effective vaccine candidates to induce anti-cancer immune responses.

Cysteine cathepsins are important proteases that are highly upregulated in cancers and other diseases. While their reported location is mostly endolysosomal, some evidence shows their nuclear localization and involvement in the cell cycle. We aim to generate tools to investigate the involvement of cathepsins in the cell cycle progression. To investigate nuclear cathepsin activity, we designed nucleus-directed quenched activity-based probes (qABPs) by attaching cell-penetrating peptides (CPPs). qABPs are active-site-directed compounds that enable direct real-time monitoring of enzyme activity by the covalent linkage between the probe and the enzyme's active site. Biochemical evaluation of the CPP-qABPs showed potent and selective probes; cell fractionation, multimodal flow cytometry-imaging, and time-lapse movies demonstrated nuclear cathepsin activity in living cells. Interestingly, these probes reveal a spatiotemporal pattern, a surge of nuclear cathepsin just before mitosis, suggesting yet unrevealed roles of cathepsin in cell division. In summary, these nuclear-directed qABPs serve as unique scientific tools to unlock the hidden features of cysteine proteases and to understand their involvement in cell division and cancer.

Background and Objectives: Hyperbaric oxygen therapy (HBOT) has shown promise in managing complications due to cancer treatments, particularly those related to radiotherapy and surgery. Despite its clinical benefits, concerns persist regarding its potential to influence cancer progression. This study aimed to evaluate the safety and clinical outcomes of HBOT in patients with active or previously treated solid tumors. Methods: A retrospective analysis was conducted on patients with solid tumors who underwent at least five HBOT sessions. Comprehensive data, including patient demographics, cancer type, total number of HBOT sessions, imaging findings, and clinical outcomes (recurrence, metastasis, and mortality), were collected. Descriptive statistics and the relationship between the number of HBOT sessions and long-term cancer outcomes were analyzed. Results: This study included 45 patients (median age: 64 years; 60% male) who received a median of 27 HBOT sessions. At initiation, 27.9% of the patients were classified as cured, 53.5% were in remission, and 18.6% had active cancer. Over a median follow-up period of 783 days, 8.7% experienced recurrence, 2.7% had persistent active cancer, and 59.5% had no recurrence. No HBOT-related complications were observed during the course of HBOT. Statistical analyses revealed no significant correlations between the number of HBOT sessions and metastasis (p = 0.213) or mortality (p = 0.881). Conclusions: HBOT appears to be a safe and effective adjunctive therapy for managing complications in patients with solid tumors. No evidence was found to suggest HBOT contributes to tumor progression, recurrence, or metastasis. Future prospective studies with larger cohorts are needed to confirm these results and further evaluate the therapeutic role of HBOT in oncology.

Head and neck squamous cell carcinoma (HNSCC) remains a challenge due to limited prognostic biomarkers and therapeutic options. The tumor microenvironment (TME), particularly the desmoplastic reaction (DR) characterized by stromal fibrosis, plays a crucial role in cancer progression and resistance to therapy. This review aims to summarize the biological significance of DR in HNSCC initiation, progression, and treatment resistance. Histologically, DR in HNSCC correlates with invasion patterns and clinical outcomes, affecting disease-free and overall survival. The interaction between cancer-associated fibroblasts (CAFs) and TME influences immune responses, including resistance to immunotherapy. Notably, human papillomavirus-driven HNSCC exhibits distinct DR characteristics that further influence the prognosis. DR promotes epithelial-mesenchymal transition and cancer cell invasion through CAF-mediated extracellular matrix remodeling and signaling pathways such as transforming growth factor-beta. DR also affects bone invasion and chemotherapy resistance by modulating stromal responses. Therapeutic strategies targeting DR and stromal components show promise in overcoming therapeutic resistance including resistance to immune checkpoint inhibitors. Understanding the role of DR in HNSCC biology and its impact on treatment response is critical to developing effective therapeutic interventions.

The intricate regulatory mechanisms governing TGF-β1 expression play pivotal roles in tumor progression. Key proteins such as FKBP1A, SMAD6, and SMAD7 trigger this process, modulating cell growth inhibition via p15INK4b and p21CIP1 induction. Despite TGF-β's tumor-suppressive functions, cancer cells adeptly evade its effects, fueling disease advancement. Tumor microenvironmental TGF-β1 prompts epithelial-mesenchymal transition (EMT), facilitated by transcription factors like slug, twist-1, and snail. Notably, cancer-associated fibroblasts (CAFs) amplify this effect by secreting TGF-β1, fostering drug resistance. Of particular concern is the resistance observed with BRAF/MEK inhibitors (BRAFi/MEKi), highlighting the clinical significance of TGF-β signaling in cancer therapeutics. However, emerging interest in natural anti-cancer agents, with their distinct pharmacological actions on signaling proteins offers promising avenues for therapeutic intervention. This review emphasizes the multifaceted interplay between TGF-β signaling, tumor microenvironment dynamics, and therapeutic resistance mechanisms, illuminating potential targets for combating cancer progression by plant-derived-natural-bioactive compounds. However, this review additionally explores the currently available advanced methods for detecting various types of cancer. Not only that, but it also discussed the function of plant-derived compounds in clinical aspects, as well as its limitations.

Numerous studies have investigated the molecular mechanisms and signalling pathways underlying cancer metastasis, as there is still no effective treatment for this terminal stage of the disease. However, the exact processes that enable primary cancer cells to acquire a metastatic phenotype remain unclear. Increasing attention has been focused on the fusion of cancer cells with myeloid cells, a phenomenon that may result in hybrid cells, so-called Tumour Hybrid Cells (THCs), with enhanced migratory, angiogenic, immune evasion, colonisation, and metastatic properties. This process has been shown to potentially drive tumour progression, drug resistance, and cancer recurrence. In this review, we explore the potential mechanisms that govern cancer cell fusion, the molecular mediators involved, the metastatic characteristics acquired by fusion-derived hybrids, and their clinical significance in human cancer. Additionally, we discuss emerging pharmacological strategies aimed at targeting fusogenic molecules as a means to prevent metastatic dissemination.

The role of TGF-β signaling in the epigenetic modifications involved in ovarian cancer is not fully understood. This study investigated the relationship between TGF-β signaling, epigenetic modifications, and cellular behaviors in ovarian cancer. We found that E-cadherin, a key cell adhesion molecule, underwent epigenetic silencing via promoter DNA hypermethylation in ovarian cancer cell lines and that this was accompanied by the upregulation of vimentin, which is indicative of a mesenchymal and invasive phenotype. DNA-demethylating agents restored E-cadherin expression, which suggests that TGF-β signaling mediates this epigenetic silencing. Overexpression of SMAD7, an inhibitory component of TGF-β signaling, reversed E-cadherin silencing, which suggests a role of SMAD7 in modulating the epigenetic status. Functionally, SMAD7 overexpression inhibited the migration and invasion in ovarian cancer cells, which suggests its therapeutic potential for suppressing metastasis. Clinically, ovarian cancer patients with high SMAD7 expression had significantly longer disease-free survival. Mechanistically, SMAD7 overexpression decreased the acetylation of H3K9 and the binding of the transcriptional repressor TWIST1 at the E-cadherin promoter, which promoted its demethylation and reactivation. Disruption of TGF-β signaling upregulated SMAD4 target genes, which are silenced by epigenetic mechanisms, a finding that suggests broader therapeutic implications. Overall, our results provide insights into the role of TGF-β-mediated epigenetic regulation in ovarian cancer metastasis and underscore the therapeutic potential of targeting TGF-β signaling and its downstream effectors. Further research is needed to elucidate the underlying mechanisms and validate these therapeutic strategies.

This study explores the mechanisms underlying chemotherapy resistance in ovarian cancer (OC) using doxorubicin (DOX) and topotecan (TOP)-resistant cell lines derived from the drug-sensitive A2780 ovarian cancer cell line. Both two-dimensional (2D) monolayer cell cultures and three-dimensional (3D) spheroid models were employed to examine the differential drug responses in these environments. The results revealed that 3D spheroids demonstrated significantly higher resistance to DOX and TOP than 2D cultures, suggesting a closer mimicry of in vivo tumour conditions. Molecular analyses identified overexpression of essential drug resistance-related genes, including MDR1 and BCRP, and extracellular matrix (ECM) components, such as MYOT and SPP1, which were more pronounced in resistant cell lines. MDR1 and BCRP overexpression contribute to chemotherapy resistance in OC by expelling drugs like DOX and TOP. Targeting these transporters with inhibitors or gene silencing could improve drug efficacy, making them key therapeutic targets to enhance treatment outcomes for drug-resistant OC. The study further showed that EMT-associated markers, including VIM, SNAIL1, and SNAIL2, were upregulated in the 3D spheroids, reflecting a more mesenchymal phenotype. These findings suggest that factors beyond gene expression, such as spheroid architecture, cell-cell interactions, and drug penetration, contribute to the enhanced resistance observed in 3D cultures. These results highlight the importance of 3D cell culture models for a more accurate representation of tumour drug resistance mechanisms in ovarian cancer, providing valuable insights for therapeutic development.

Tumors constantly shed cancer cells that are considered the mediators of metastasis via the blood stream. Analysis of circulating cells and circulating cell-free DNA (cfDNA) in liquid biopsies, mostly taken from peripheral blood, have emerged as powerful biomarkers in oncology, as they enable the detection of genomic aberrations. Similarly, liquid biopsies taken from pregnant women serve as prenatal screening test for an abnormal number of chromosomes in the fetus, e.g., via the analysis of microchimeric fetal cells and cfDNA circulating in maternal blood. Liquid biopsies are minimally invasive and, consequently, associated with reduced risks for the patients. However, different challenges arise in oncology and pregnancy-acquired liquid biopsies with regard to the analyte concentration and biological (background) noise among other factors. In this review, we highlight the unique biological properties of circulating tumor cells (CTC), summarize the various techniques that have been developed for the enrichment, detection and analysis of CTCs as well as for analysis of genetic and epigenetic aberrations in cfDNA and highlight the range of possible clinical applications. Lastly, the potential, but also the challenges of liquid biopsies in oncology as well as their translational value for the analysis of pregnancy-acquired microchimerism are discussed.

Lysyl oxidase (LOX), a copper-containing secretory oxidase, plays a key role in the regulation of extracellular stiffness through cross-linking with collagen and elastin. Among the LOX family of enzymes, LOX-like 4 (LOXL4) exhibits pro-tumor and anti-tumor properties; therefore, the functional role of LOXL4 in tumor progression is still under investigation. Here, we first determined that transforming growth factor-β1 (TGF-β1) significantly decreased LOXL4 expression in human breast cancer MDA-MB-231 cells, which suggested that decreased LOXL4 may participate in tumor progression. In this study, we also investigated how TGF-β1 decreases LOXL4 expression. TGF-β1-induced intracellular reactive oxygen species (ROS) played a role in LOXL4 protein expression but had no effect on LOXL4 mRNA levels. The proteasomal inhibitor, bortezomib, significantly suppressed TGF-β1-mediated LOXL4 reduction, which indicated that TGF-β1 facilitates LOXL4 proteasomal degradation. Furthermore, bortezomib inhibited TGF-β1-induced MEK/ERK pathways which are involved in LOXL4 reduction and TGF-β1-mediated cell migration. Finally, we also determined the potential role of N-glycosylation in LOXL4 secretion. We found that the dysregulation of N-glycosylation may be involved in the reduction in LOXL4 secretion. Overall, bortezomib is expected to inhibit TNBC progression by inhibiting both the MEK/ERK and proteasomal degradation pathways, which regulate LOXL4 expression.

Transforming growth factor-beta (TGF-β) plays a pivotal role in breast development by modulating tissue composition during the developmental phase. The TGFβ type II receptor (TGFβ RII) is implicated in breast cancer and represents a valuable therapeutic target. Due to the off-target side effects of many existing TGFβI/TGFβ RII inhibitors, a more targeted approach to drug discovery is necessary. This study used computational modeling and molecular dynamics simulations to screen the ChemBridge small molecule library against TGFβ RII.

This study employed high-throughput virtual screening, molecular dynamics simulations, and binding free energy calculations to identify potential inhibitors targeting TGF-β RII. MDA-MB 231 and MCF-7 breast cancer cells were used in anti-proliferative, tans-endothelial migration, and flow cytometric assays for in vitro validations.

We identified 8-(2-methylphenyl)-9H-benzo[f]indeno[2,1-c]quinolin-9-one (C-5635020) as a potent and selective inhibitor. Protein-ligand modeling analysis revealed that C-5635020 targets the kinase domain of TGFβ RII with superior binding affinities compared to the standard drug, staurosporine. Computational results suggest that C-5635020 selectively binds and inhibits TGFβ RII activity, thereby controlling cell proliferation in breast cancer. In vitro, experiments corroborated these predictions, where C-5635020 inhibited TGFβ RII and p-Smad 2/3 positive population in MDAMB-231 and MCF-7 cells. The compound dose-dependently inhibited cell proliferation, trans-endothelial migration, and increased apoptosis in both breast cancer cell lines.

The strong binding affinity, stability, and favorable thermodynamics of C-5635020 with established in vitro efficacy highlight its potential as a lead compound for further preclinical and clinical developments for breast cancer treatment.

Breast cancer (BC) is a significant contributor to cancer-related deaths in women, and it has complex connections with obesity and aging. This review explores the interaction between obesity and aging in relation to the development and progression of BC, focusing on the controlling role of microRNAs (miRNAs). Obesity, characterized by excess adipose tissue, contributes to a proinflammatory environment and metabolic dysregulation, which are important in tumor development. Aging, associated with cellular senescence and systemic changes, further exacerbates these conditions. miRNAs, small noncoding RNAs that regulate gene expression, play key roles in these processes, impacting pathways involved in cell proliferation, apoptosis, and cancer metastasis, either as tumor suppressors or oncogenes. Importantly, specific miRNAs are implicated in mediating the impact of obesity and aging on BC. Exploring the regulatory networks controlled by miRNAs provides valuable information on new targets for therapy and predictive markers, demonstrating the potential for using miRNA-based interventions to treat BC in obese and elderly individuals. This review emphasizes the importance of integrated research strategies to understand the complex connections between obesity, aging, and miRNA regulation in BC.

We previously isolated a cDNA clone for galactosylceramide expression factor 1, which is the rat homologue of hepatocyte-growth-factor-regulated tyrosine kinase substrate (HGS) and induces galactosylceramide expression and morphological changes in COS-7 cells, and reported that overexpression of HGS induced morphological changes in canine kidney epithelial MDCK cells. HGS is a component of the endosomal sorting complexes required for transport machinery that mediates endosomal multivesicle body formation. In this study, the overexpression of HGS induced epithelial-mesenchymal transition and caused transformation in MDCK cells, whereas the overexpression of a coiled-coil domain of HGS inhibited induction of epithelial-mesenchymal transition by HGF stimulation. The overexpression of HGS in mouse melanoma B16 cells and human colorectal cancer COLO205 cells promoted cancer characteristic anchorage-independent cell growth ability and tumor growth, whereas the overexpression of the coiled-coil domain of HGS in these cells suppressed them. The oligopeptide OP12-462 constituting the coiled-coil domain suppressed the anchorage-independent cell growth ability and tumor growth of COLO205 cells. The coiled-coil domain of HGS and OP12-462 are novel tumor growth inhibitors that do not directly destroy cancer cells but rather inhibit only the anchorage-independent cell growth ability of cancer cells.

Epithelial ovarian cancer (EOC) remains a leading cause of gynecologic cancer mortality. Despite advances in treatment, metastatic progression and resistance to standard therapies significantly worsen patient outcomes. Epithelial-mesenchymal transition (EMT) is a critical process in metastasis, enabling cancer cells to gain invasive and migratory capabilities, often driven by changing miRNA expression involved in the regulation of pathological processes like drug resistance. Targeted therapies like PARP inhibitors (PARPi) have improved outcomes, particularly in BRCA-mutated and DNA repair-deficient tumors; however, resistance and limited efficacy in advanced stages remain challenges. Recent studies highlight the potential synergy of PARPi with DNA damage response (DDR) inhibitors, such as ATR and CHK1 inhibitors, which disrupt cancer cell survival pathways under stress. This study investigated the combined effects of olaparib with ATR and CHK1 inhibitors (ATRi and CHK1i) on migration, invasion, and EMT-related protein expression and miRNA expression in ovarian cancer cell lines OV-90 and SKOV-3. The results demonstrated enhanced cytotoxicity, inhibition of migration and invasion, and modulation of miRNAs linked to metastasis. These findings suggest that combination therapies targeting DNA repair and cell cycle pathways may offer a novel, more effective approach to managing advanced EOC and reducing metastatic spread.

The tumor microenvironment (TME) is integral to cancer progression, impacting metastasis and treatment response. It consists of diverse cell types, extracellular matrix components, and signaling molecules that interact to promote tumor growth and therapeutic resistance. Elucidating the intricate interactions between cancer cells and the TME is crucial in understanding cancer progression and therapeutic challenges. A critical process induced by TME signaling is the epithelial-mesenchymal transition (EMT), wherein epithelial cells acquire mesenchymal traits, which enhance their motility and invasiveness and promote metastasis and cancer progression. By targeting various components of the TME, novel investigational strategies aim to disrupt the TME's contribution to the EMT, thereby improving treatment efficacy, addressing therapeutic resistance, and offering a nuanced approach to cancer therapy. This review scrutinizes the key players in the TME and the TME's contribution to the EMT, emphasizing avenues to therapeutically disrupt the interactions between the various TME components. Moreover, the article discusses the TME's implications for resistance mechanisms and highlights the current therapeutic strategies toward TME modulation along with potential caveats.

Triple-negative breast cancer (TNBC) is one of the most difficult subtypes of breast cancer to treat due to its distinct clinical and molecular characteristics. Patients with TNBC face a high recurrence rate, an increased risk of metastasis, and lower overall survival compared to other breast cancer subtypes. Despite advancements in targeted therapies, traditional chemotherapy (primarily using platinum compounds and taxanes) continues to be the standard treatment for TNBC, often with limited long-term efficacy. TNBC tumors are heterogeneous, displaying a diverse mutation profile and considerable chromosomal instability, which complicates therapeutic interventions. The development of chemoresistance in TNBC is frequently associated with the process of epithelial-mesenchymal transition (EMT), during which epithelial tumor cells acquire a mesenchymal-like phenotype. This shift enhances metastatic potential, while simultaneously reducing the effectiveness of standard chemotherapeutics. It has also been suggested that EMT plays a central role in the development of cancer stem cells. Hence, there is growing interest in exploring small-molecule inhibitors that target the EMT process as a future strategy for overcoming resistance and improving outcomes for patients with TNBC. This review focuses on the progression and drug resistance of TNBC with an emphasis on the role of EMT in these processes. We present TNBC-specific and EMT-related molecular features, key EMT protein markers, and various signaling pathways involved. We also discuss other important mechanisms and factors related to chemoresistance in TNBC within the context of EMT, highlighting treatment advancements to improve patients' outcomes.

Complex tissue flows in epithelia are driven by intra- and inter-cellular processes that generate, maintain, and coordinate mechanical forces. There has been growing evidence that cell shape anisotropy, manifested as nematic order, plays an important role in this process. Here we extend an active nematic vertex model by replacing substrate friction with internal viscous dissipation, dominant in epithelia not supported by a substrate or the extracellular matrix, which are found in many early-stage embryos. When coupled to cell shape anisotropy, the internal viscous dissipation allows for long-range velocity correlations and thus enables the spontaneous emergence of flows with a large degree of spatiotemporal organisation. We demonstrate sustained flow in epithelial sheets confined to a channel, providing a link between the cell-level vertex model of tissue dynamics and continuum active nematics, whose behaviour in a channel is theoretically understood and experimentally realisable. Our findings also show a simple mechanism that could account for collective cell migration correlated over distances large compared to the cell size, as observed during morphogenesis.

Metastasis causes most cancer deaths and reflects transitions from primary tumor escape to seeding and growth at metastatic sites. Epithelial-to-mesenchymal transition (EMT) is important early in metastasis to enable cancer cells to detach from neighboring cells, become migratory, and escape the primary tumor. While different phases of metastasis expose cells to variable nutrient environments and demands, the metabolic requirements and plasticity of each step are uncertain. Here we show that EMT and primary tumor escape are stimulated by disrupted oxidative metabolism. Using Renal Cell Carcinoma (RCC) patient samples, we identified the mitochondrial electron transport inhibitor NDUFA4L2 as upregulated in cells undergoing EMT. Deletion of NDUFA4L2 enhanced oxidative metabolism and prevented EMT and metastasis while NDUFA4L2 overexpression enhanced these processes. Mechanistically, NDUFA4L2 suppressed oxidative phosphorylation and caused citric acid cycle intermediates to accumulate, which modified chromatin accessibility of EMT-related loci to drive primary tumor escape. The effect of impaired mitochondrial metabolism to drive EMT appeared general, as renal cell carcinoma patient tumors driven by fumarate hydratase mutations with disrupted oxidative phosphorylation were highly metastatic and also had robust EMT. These findings highlight the importance of dynamic shifts in metabolism for cell migration and metastasis, with mitochondrial impairment driving early phases of this process. Understanding mitochondrial dynamics may have important implications in both basic and translational efforts to prevent cancer deaths.

Triple-negative breast cancer (TNBC) remains a challenging subtype due to its aggressive nature and limited treatment options. This study investigated the potential synergistic effects of Korean mistletoe lectin (Viscum album L. var. coloratum agglutinin, VCA) and cisplatin on MDA-MB-231 TNBC cells using both 2D and 3D culture models. In 2D cultures, the combination of VCA and cisplatin synergistically inhibited cell proliferation, induced apoptosis, and arrested the cell cycle at the G2/M phase. Also, the combination treatment significantly reduced cell migration and invasion. Gene expression analysis showed significant changes in specific genes related to apoptosis (Bax, Bcl-2), metastasis (MMP-2, MMP-9), and EMT (E-cadherin, N-cadherin). Three-dimensional spheroid models corroborated these findings, demonstrating enhanced cytotoxicity and reduced invasion with the combination treatment. Significantly, the 3D models exhibited differential drug sensitivity compared to 2D cultures, emphasizing the importance of utilizing physiologically relevant models in preclinical studies. The combination treatment also reduced the expression of angiogenesis-related factors VEGF-A and HIF-1α. This comprehensive study provides substantial evidence for the potential of VCA and cisplatin combination therapy in TNBC treatment and underscores the significance of integrating 2D and 3D models in preclinical cancer research.

Cutaneous squamous cell carcinoma (cSCC) is an increasingly common malignancy of the skin and the leading cause of death from skin cancer in adults over the age of 85. Fibroblast growth factor receptor 2 (FGFR2) has been identified as an important effector of signaling pathways that lead to the growth and development of cSCC. In recent years, there have been numerous studies evaluating the role FGFR2 plays in multiple cancers, its contribution to resistance to anticancer therapy, and new drugs that may be used to inhibit FGFR2. This review will provide an overview of our current understanding of FGFR2 and potential mechanisms in which we can target FGFR2 in cSCC. The goals of this review are the following: (1) to highlight our current knowledge of the role of FGFR2 in healthy skin and contrast this with its role in the development of cancer; (2) to further explain the specific molecular mechanisms that FGFR2 uses to promote tumorigenesis; (3) to describe how FGFR2 contributes to more invasive disease; (4) to describe its immunosuppressive effects in skin; and (5) to evaluate its effect on current anticancer therapy and discuss therapies on the horizon to target FGFR2 related malignancy.

Squamous cell carcinoma of the head and neck (SCCHN) is an aggressive disease with poor prognosis. It is known that the activation of STAT3 signaling pathways promotes the development and progression of this neoplasia and it has been described the role of PTPRT as a negative regulator of STAT3. Then, we have evaluated the impact of them as biomarkers of outcome in a series of patients with recurrent and/or metastatic SCCHN treated with weekly paclitaxel-plus-cetuximab (ERBITAX) regimen.

Between 2008 and 2017, 52 patients with recurrent/metastatic SCCHN were treated with ERBITAX at our center, 34 of whom had available tumor samples. Phosphorylated STAT3 (pSTAT3) protein expression was analyzed by immunohistochemistry, STAT3 mRNA expression by qPCR, and PTPRT promoter methylation by methylation-specific PCR. Molecular results were correlated with response rate (RR), progression-free survival (PFS), and overall survival (OS).

pSTAT3 overexpression was detected in 67% and PTPRT promoter hypermethylation in 41% of tumor samples. PTPRT promoter hypermethylation showed a trend towards an association with lower RR (21% vs. 60%; p = 0.06). A lower RR was also observed in patients with pSTAT3 overexpression (36% vs. 54%) and in those with high STAT3 mRNA levels (43% vs. 64%), but these differences did not reach statistical significance. PTPRT promoter hypermethylation correlated with pSTAT3 overexpression (p = 0.009) but not with STAT3 mRNA overexpression. OS and PFS was shorter in patients with activated STAT3, but the difference did not reach statistical significance.

Although this was a relatively small retrospective study, it provides preliminary indications of the potential role of the STAT3 pathway on outcome in SCCHN and confirms that PTPRT acts as a negative regulator of STAT3. Our findings warrant investigation in a larger patient cohort to determine if inactivating this pathway through specific targeted treatments could improve outcomes in recurrent/metastatic SCCHN patients.

Oral squamous cell carcinoma (OSCC) is a common malignancy often associated with poor prognosis due to chemoresistance. In this study, we investigated whether arecoline, a major alkaloid in betel nuts, can stimulate aldo-keto reductase family 1 member B10 (AKR1B10) levels in OSCC, promoting cancer stemness and leading to resistance to cisplatin (CDDP)-based chemotherapy.

Gain- and Loss- of AKR1B10 functions were analyzed using WB and q-PCR of OSCC cells. Stemness, epithelial mesenchymal transition (EMT) markers, and CDDP drug resistance in overexpressed AKR1B10 were also identified.

Upregulated AKR1B10 in OSCC significantly increased cell motility and aggregation. The results also showed that the canonical TGF-β1-Smad3 pathway was involved in arecoline-induced AKR1B10 expression, further increasing cancer stemness with CDDP resistance via the Snail-dependent EMT pathway. Moreover, oleanolic acid (OA) and ROS/RNS (reactive oxygen/nitrogen species) inhibitors effectively reversed AKR1B10-induced CDDP-resistance.

Arecoline-induced ROS/RNS to hyper-activate AKR1B10 in tumor sphere cells via the TGF-β1-Smad3 pathway. Furthermore, AKR1B10 enhanced CDDP resistance in OSCC cells via EMT-inducing markers. Finally, Finally, OA may efficiently target CDDP resistance, reverse stemness in OSCC cells, and have the potential as a novel anticancer drug.

E-cadherin is a transmembrane protein and central component of adherens junctions (AJs). The extracellular domain of E-cadherin forms homotypic interactions with E-cadherin on adjacent cells, facilitating the formation of cell-cell adhesions, known as AJs, between neighbouring cells. The intracellular domain of E-cadherin interacts with α-, β- and p120-catenins, linking the AJs to the actin cytoskeleton. Functional AJs maintain epithelial tissue identity and integrity. Transcriptional downregulation of E-cadherin is the first step in epithelial-to-mesenchymal transition (EMT), a process essential in development and tissue repair, which, in breast cancer, can contribute to tumour progression and metastasis. In addition, loss-of-function mutations in E-cadherin are a defining feature of invasive lobular breast cancer (also known as invasive lobular carcinoma (ILC)), the second most common histological subtype of breast cancer. ILC displays a discohesive, single-file invasive growth pattern due to the loss of functional AJs. Despite being so prevalent, until recently there has been limited ILC-focused research and historically ILC patients have often been excluded from clinical trials. Despite displaying a number of good prognostic indicators, such as low grade and high rates of estrogen receptor positivity, ILC patients tend to have similar or poorer outcomes relative to the most common subtype of breast cancer, invasive ductal carcinoma (IDC). In ILC, E-cadherin loss promotes hyperactivation of growth factor receptors, in particular insulin-like growth factor 1 receptor, anoikis resistance and synthetic lethality with ROS1 inhibition. These features introduce clinical vulnerabilities that could potentially be exploited to improve outcomes for ILC patients, for whom there are currently limited tailored treatments available.

Crohn's disease (CD) is a chronic inflammatory condition of the bowel that remarkably impairs a patient's quality of life and often has a poor prognosis. Perianal fistulizing CD (PFCD) is one of the most common parenteral symptoms of CD and a huge challenge for the management of this illness. This study aimed to elucidate the molecular mechanisms underlying PFCD and identify potential biomarkers to advance our understanding and management of this condition.

Transcriptome sequencing was performed using the control and PFCD groups to investigate the mechanisms of PFCD development. The expression of tumor necrosis factor receptor-associated factor 5 (TRAF5), nuclear factor-kappa B (NF-κB), and interleukin 13 (IL-13) messenger ribonucleic acid (mRNAs) was detected by quantitative polymerase chain reaction (qPCR). Pathological morphology was observed using hematoxylin and eosin staining. The expression of TRAF5, Epithelial Cadherin (E-cadherin), Snail family transcriptional repressor 1 (SNAIL1), and vimentin protein was detected by immunohistochemistry. Following the knockdown of TRAF5 in human tumor-29 (HT-29) cells, the effects on cell proliferation and migration were assessed using the cell counting kit-8 and Transwell assays. The expression levels of crucial markers were analyzed by qPCR, Western blot, and immunohistochemistry.

Transcriptomic sequencing revealed a significant upregulation of TRAF5 in the PFCD group, accompanied by elevated mRNA levels of NF-κB and IL-13 compared with those in the control group. In addition, the PFCD group exhibited increased expression of TRAF5, SNAIL, and vimentin and marked reduction in E-cadherin levels, indicating that PFCD may facilitate epithelial-mesenchymal transition (EMT). Knocking down TRAF5 in HT-29 cells reduced cell proliferation and migration; inhibited NF-κB and IL-13 mRNAs, SNAIL1, and vimentin levels; and promoted E-cadherin levels.

The development of PFCD was associated with EMT, and TRAF5 was a key gene of PFCD. Knocking down TRAF5 alleviated the EMT promotion of PFCD, indicating that TRAF5 drove the development of PFCD through EMT.

Cancer, a complex and heterogeneous disease, continues to be a major global health concern. Despite advancements in diagnostics and therapeutics, the aggressive nature of certain cancers remain a significant challenge, necessitating a deeper understanding of the underlying molecular mechanisms driving their severity and progression. Cancer severity and progression depend on cellular properties such as cell migration, cell division, cell shape changes, and intracellular transport, all of which are driven by dynamic cellular microtubules. Dynamic properties of microtubules, in turn, are regulated by an array of proteins that influence their stability and growth. Among these regulators, End Binding (EB) proteins stand out as critical orchestrators of microtubule dynamics at their growing plus ends. Beyond their fundamental role in normal cellular functions, recent research has uncovered compelling evidence linking EB proteins to the pathogenesis of various diseases, including cancer progression. As the field of cancer research advances, the clinical implication of EB proteins role in cancer severity and aggressiveness become increasingly evident. This review aims to comprehensively explore the role of microtubule-associated EB proteins in influencing the severity and aggressiveness of cancer. We also discuss the potential significance of EB as a clinical biomarker for cancer diagnosis and prognosis and as a target for therapeutic intervention.

Colorectal cancer (CRC) is the third diagnosed cancer worldwide. Forty-four percent of metastatic colorectal cancer patients were diagnosed at an early stage. Despite curative resection, approximately 40% of patients will develop metastases within a few years. Previous studies indicate the presence of cancer stem cells (CSCs) and their contribution to CRC progression and metastasis. miRNAs deregulation plays a role in CSCs formation and in tumor development. In light of previous studies, we investigated the role of miR-486-5p to understand its role in CSC better.

The expression of miR-486-5p was assessed in adherent cells and spheres generated from two CRC cell lines to observe the difference in expression in CSC-enriched spheroids. Afterward, we overexpressed and underexpressed this miRNA in adherent and sphere cultures through the transfection of a miR-486-5p mimic and a mimic inhibitor.

The results demonstrated that miR-486-5p exhibited a notable downregulation in CSC models, and its overexpression led to a significant decrease in colony size.

In this study, we confirmed that miR-486-5p plays an oncosuppressive role in CRC, thereby advancing our understanding of the role of this microRNA in the CSC phenotype.