Journal of Gene Medicine最新文献

Ovarian cancer remains a leading cause of gynecological malignancy-related deaths, necessitating the identification of novel molecular pathways driving tumor progression. Utilizing a data-driven approach, we conducted bioinformatic analyses of TCGA and GEO datasets, identifying a significant upregulation of CXCL14 in ovarian cancer tissues, which correlates with poor patient survival. Functional assays demonstrated that overexpression of CXCL14 enhances ovarian cancer cell proliferation, invasion, and autophagy. Mechanistically, CXCL14 activates the canonical NF-κB signaling pathway by inducing phosphorylation and degradation of IκBα, leading to phosphorylation and nuclear translocation of p65. Importantly, we identified IKBKE as a critical kinase mediating CXCL14-induced activation of the canonical NF-κB pathway through phosphorylation of IκBα. Knockdown of IKBKE effectively attenuates CXCL14-driven NF-κB activation, thereby suppressing cell proliferation, invasion, and autophagy. In vivo, CXCL14 overexpression markedly enhances ovarian tumor growth, accompanied by increased levels of IKBKE and phosphorylated p65. These findings elucidate a novel regulatory axis, CXCL14/IKBKE/NF-κB, in ovarian cancer progression, highlighting CXCL14 as a potential therapeutic target for ovarian cancer treatment.

Ovarian cancer (OC) is still one of the most serious gynecologic malignancies in the world. It is characterized by a significant likelihood of recurrence and resistance to conventional therapies and a lack of efficient screening techniques. MicroRNAs (miRNAs) are small, noncoding RNA molecules that exert pivotal functions in modulating gene expression. miRNAs are improperly regulated in OC, contributing to tumor onset, progression, metastasis, and resistance to chemotherapeutics. As a result, miRNAs are promising therapeutic targets for the treatment of OC. Recently, natural products derived from plants and other sources have drawn more interest because of their potential to modulate miRNA expression. A variety of bioactive substances, such as curcumin, quercetin, and others, have shown the ability to either promote tumor-suppressing miRNAs or suppress tumor-promoting miRNAs. These substances have a great deal of promise for improving the effectiveness of traditional chemotherapy, lowering adverse effects, and providing more individualized treatment plans. Additionally, their capacity to target several miRNAs implicated in cancer-related pathways offers a multimodal strategy for treating OC. We can upgrade the potential therapeutic options for OC and other cancers by exploring novel natural products with miRNA-modulating effects. However, further research is needed to clinically translate miRNA-based therapeutics employing natural compounds, especially in the areas of safety, bioavailability, and drug delivery methods. This review emphasized the implications of miRNAs in OC, the impact of natural products on miRNA regulations, and the potential for incorporating these natural substances into clinical practice for individualized and successful OC treatments.

Vitiligo involves melanocyte loss, potentially due to oxidative stress, immune dysfunction, and genetics. This article examines microRNAs (miRNAs), noncoding RNAs crucial for gene expression regulation, as they act as molecular switches that can activate or deactivate genes upon translation. It identifies modified miRNA levels in the skin, blood, immune cells, and exosomes of vitiligo patients. These miRNAs are essential for melanocyte viability and for modulating oxidative stress and immunological responses. Specific miRNAs may function as diagnostic or prognostic biomarkers. The review offers an in-depth comprehension of the crucial functions of miRNAs in development.

Lung adenocarcinoma (LUAD), a major subtype of non–small-cell lung cancer, exhibits high incidence and mortality rates. Radiotherapy is a critical treatment modality for LUAD, yet its efficacy is often compromised by radiotherapy resistance. (−)-Epicatechin (EC), a natural flavanol derived from Fagopyrum cymosum, has been reported to enhance radiosensitivity in various cancers. However, its specific role and underlying mechanisms in LUAD radiotherapy resistance remain unclear. In this study, we established radiotherapy-resistant cell lines A549R and NCI-H520R by repeatedly irradiating A549 and NCI-H520 cells with gradient doses of X-rays. Furthermore, a xenograft tumor model was constructed by subcutaneously inoculating A549R cells into the left dorsal region of nude mice. The results demonstrated that the forkhead box M1 (FOXM1)—a key oncoprotein implicated in lung cancer proliferation, invasion, and therapy resistance—was significantly upregulated in LUAD tissues and radiotherapy-resistant A549R cells. Knockdown of FOXM1 enhanced radiosensitivity in A549R cells, promoted radiation-induced apoptosis, and suppressed cell proliferation. EC effectively potentiated the radiotherapy response of A549R cells in vitro and attenuated radiotherapy resistance while inhibiting tumor growth in vivo. Mechanistically, EC downregulated ALKBH5, an m6A demethylase known to participate in cancer biology by regulating mRNA demethylation, thereby promoting m6A methylation of FOXM1 mRNA and subsequently suppressing FOXM1 expression, ultimately mitigating radiotherapy resistance in LUAD. This study reveals a novel mechanism by which EC enhances radiosensitivity in LUAD via the ALKBH5/FOXM1 axis, offering a potential therapeutic strategy to overcome radiotherapy resistance in LUAD.

Ovarian cancer remains a leading cause of gynecologic cancer mortality, in part due to the persistence of ovarian cancer stem cells (OCSCs) that drive tumor recurrence, metastasis, and drug resistance. Anisomycin, a natural antibiotic derived from Streptomyces coelicolor, has previously been shown to exert antitumor effects, but the mechanisms by which it targets OCSCs remain unclear. In this study, primary human OCSCs were isolated and treated with anisomycin to investigate its biological and molecular effects. Cell proliferation, apoptosis, migration, and colony formation were assessed in vitro, and tumorigenicity was evaluated in xenograft mouse models. Transcriptomic, biochemical, and molecular assays were performed to identify downstream pathways. Anisomycin treatment markedly inhibited proliferation and promoted senescence and cell death of OCSCs. Mechanistically, anisomycin induced upregulation of microRNA-340, which in turn suppressed the deSUMOylating enzyme SENP6. This repression increased SUMOylation of key senescence-related proteins, including p53 and p16, leading to stabilization of their expression and enforcement of cell-cycle arrest. Overexpression of microRNA-340 reproduced these effects, both in vitro and in vivo, confirming its central role in mediating anisomycin activity. Bioinformatic analyses further revealed that expression of SENP6 and senescence-associated genes correlated with disease progression and patient survival in ovarian cancer cohorts. These findings identify a previously unrecognized epigenetic mechanism by which anisomycin induces senescence and death in OCSCs, suggesting that targeting the microRNA-340/SENP6/SUMOylation pathway may represent a promising therapeutic approach.

Research on molecular classification of lung cancer based on transcriptomic features has achieved remarkable progress. The complementary information provided by distinct molecular profiles has motivated the integration of multi-omics datasets to refine the classification system for lung cancer. In this study, we employed a computational pipeline incorporating 10 clustering algorithms to integrate multi-omics datasets from lung adenocarcinoma (LUAD) patients, combined with 10 machine learning methods, leading to the identification of high-resolution molecular subtypes and the development of a consensus machine learning–driven signature (CMLS) with robust predictive performance. Our findings reveal that the CS1 subtype is associated with more favorable prognosis and enhanced immune responsiveness. Furthermore, a CMLS model constructed from 26 core genes demonstrated strong prognostic predictive power. Patients with high CMLS scores exhibited lower infiltration of CD8⁺ T cells, poorer survival, and diminished response to immunotherapy. In contrast, the low-CMLS group showed improved clinical outcomes, greater responsiveness to immunotherapy, and a tendency toward an immunologically “hot” tumor phenotype. Integrated multi-omics analysis indicated that Gremlin-1 (GREM1) acts as a key regulator within the differential screening–selected gene aberrant in neuroblastoma (DAN) family genes–mediated transforming growth factor-beta (TGF-β) signaling pathway. In conclusion, our data establish a molecular classifier that stratifies patients into distinct score groups, with those in the low-CMLS group potentially benefiting from treatment with pilaralisib.