Long non-coding RNAs (lncRNAs) are essential modulators in tumor progression. While fatty acid (FA) metabolism can potentiate tumorigenesis, colonization, and metastasis, the roles of lncRNAs in reprograming FA metabolism and regulating gastric cancer (GC) metastasis remain elusive. Whole RNA-sequencing and in silico analyses were conducted to identify clinically significant lncRNAs involved in GC metastasis. Among the identified lncRNAs, we focused on the novel lncRNA TENM3-AS1. RT-qPCR and FISH analyses revealed an increased expression of TENM3-AS1 in GC cell lines and patients. In vitro and in vivo functional experiments validated the effects of TENM3-AS1 to GC metastasis and the reprogramming of FA metabolism. ChIP, Biotinylated RNA pull-down, RIP, CHX-chase assay, ubiquitination assay, and RNA stabilization assay were employed to perceive the mechanisms underlying the effects of TENM3-AS1 in GC cells. TENM3-AS1 expression was significantly elevated in metastatic tumors and advanced primary tumors of GC patients. This increased expression was also associated with a worsened overall survival and progression-free survival. Functionally, TENM3-AS1 enhanced the migration and invasiveness of GC cells in vitro, promoted tumorigenesis and liver metastasis in vivo, and increased FA biosynthesis in GC cells. Mechanistically, our studies showed that the transcription factor EGR1 activated TENM3-AS1, which in turn upregulated the expression of FASN and hnRNPK. Furthermore, TENM3-AS1 interacted with and stabilized hnRNPK by increasing its deubiquitination. This interaction reprogrammed FA metabolism and promoted GC progression by increasing FASN mRNA stability through hnRNPK. In this study, by comparing lncRNA sequencing data from paired primary and peritoneal metastatic tumors and public transcriptome data from non-metastatic and metastatic samples, we clarified a novel lncRNA, TENM3-AS1. It was found that TENM3-AS1 was aberrantly activated in metastatic and advanced primary tumors, and was strongly correlated with a shorter survival in GC patients. Our study reveals the EGR1/TENM3-AS1/ hnRNPK/FASN axis as a novel curative target in metastatic GC.

Circular RNAs (circRNAs) are emerging as crucial regulators of the progression and metastasis of breast cancer. This review examines the dual roles of circRNAs, which act as both oncogenes and tumor suppressors, in breast cancer metastasis. CircRNAs play crucial roles in processes such as the epithelial‒mesenchymal transition (EMT), angiogenesis, immune evasion, and metabolic adaptation, facilitating cancer cell invasion, survival, and colonization in distant organs such as the brain, liver, bone, and lungs. Pro-metastatic circRNAs, such as circKIF4A and circBACH1, promote metastasis by modulating signaling pathways such as the STAT3 and PI3K/AKT pathways, whereas tumor-suppressive circRNAs, including circFOXO3 and circNFIB, inhibit metastatic progression through mechanisms such as VEGF downregulation and the suppression of arachidonic acid metabolism. Although circRNAs hold promise as biomarkers and therapeutic targets, their clinical application is impeded by challenges such as targeted delivery, off-target effects, and context-dependent roles. This review highlights the current understanding of circRNA-mediated regulation of breast cancer metastasis and emphasizes future directions, including the integration of multiomics technologies and advanced delivery systems, to increase the diagnostic and therapeutic utility of circRNAs.

Triple-negative breast cancer (TNBC) is among the most aggressive subtypes of the disease that does not express estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2. Circular RNAs (circRNAs) are a type of non-coding RNA with a circular shape formed by non-standard splicing or reverse splicing. Numerous circRNAs exhibit abnormal expression in various malignancies, showing their critical role in the emergence and growth of tumors. Recent studies have shown evidence supporting the idea that certain circRNAs regulate the proliferation and metastasis of TNBC. In addition, circRNAs alter metabolism and the immune microenvironment to promote or inhibit the development of TNBC. Notably, circRNAs may affect the efficacy of clinical drug therapy, serve as therapeutic targets, and be used as molecular biomarkers in the future. Herein, we will first summarize the biogenesis and function of circRNAs. Then, we will explain current research on circRNAs related to TNBC and their potential to serve as therapeutic targets or biomarkers for future drug development, providing a new direction and idea for TNBC therapy.

A novel copper (II) probe based on pyridinium salt was designed and synthesized, and the structure was confirmed by NMR and high-resolution mass spectrometry (HRMS). The probe exhibits strong orange fluorescent emission, and shows high selectivity for copper (II) over other cations. It may qualitatively identify copper ions from many metal cations without the use of any instruments. The fluorescent intensity at 572 nm decreases linearly with copper (II) concentration in the range of 0–10 µM. A remarkable detection limit (0.045 µM) can be achieved.

Background: Dengue virus (DENV) infection remains a global health threat with no approved small-molecule antiviral for clinical use. Luteolin, a natural flavonoid, exhibits anti-dengue activity but suffers from poor solubility and moderate potency. The 7-O position is the primary site of metabolic glucuronidation, whereas the 5-O position is sequestered by intramolecular hydrogen bonding, offering structurally distinct positions for derivatization. Methods: Five site-selective derivatives of luteolin (three 5-O- and two 7-O-substituted) were synthesized. Their anti-DENV activity was evaluated in Vero cells by qRT-PCR (measuring viral RNA abundance) and plaque assays, and cytotoxicity was determined using the CCK8 method. For mechanistic exploration, enzymatic inhibition kinetics against NS2B/NS3 and furin were measured, and target engagement was further assessed via molecular docking and cellular thermal shift assays (CETSA). Results: Among the derivatives, compound 5, bearing a 4-fluorobenzenesulfonyl group at the 7-O position, exhibited the most potent anti-DENV activity (EC ₅₀ = 0.46 μM) and the highest selectivity index (SI = 28.5), representing an 18-fold increase in antiviral potency over luteolin. In enzymatic assays, compound 5 showed preferential inhibition of the viral NS2B/NS3 protease ( K _i = 11.54 μM) over the host furin ( K _i = 93 μM). Molecular docking and thermal stabilization assays provided correlative evidence supporting target engagement with both proteases. Conclusion: Site-selective 7-O-sulfonation of luteolin yields compound 5, a derivative with improved anti-DENV activity and selectivity that shows preferential NS2B/NS3 inhibition in enzymatic assays. This study provides a structural framework for the further optimization of flavonoid-based antiviral agents.