Head and neck squamous cell carcinoma (HNSCC) presents a significant global health challenge, characterized by late-stage diagnosis and high rates of locoregional recurrence. Traditional tissue biopsy, while considered the gold standard, is invasive and often fails to capture the spatial and temporal heterogeneity of the tumor. Liquid biopsy has emerged as a transformative, noninvasive paradigm for molecular diagnostics, leveraging circulating biomarkers found in blood and saliva. This systematic review critically evaluates current evidence regarding the diagnostic accuracy, prognostic value, and molecular validity of circulating tumor cells, circulating tumor DNA (ctDNA), and the transcriptomic landscape of coding and noncoding RNAs (miRNAs, lncRNAs, and circRNAs) in HNSCC. Our review highlights the specificity of ctDNA for monitoring minimal residual disease, particularly in human papillomavirus- and Epstein-Barr virus-driven malignancies, where viral kinetics serve as sensitive biomarkers for recurrence. Furthermore, we explore the utility of “Saliva-Exosomics,” suggesting that salivary exosomes may offer high sensitivity for early-stage oral cavity lesions due to anatomical proximity. The review also synthesizes data on novel RNA species, such as tumor-educated platelets and circular RNAs, which act as stable systemic biosensors. Despite promising results, significant heterogeneity in isolation protocols and detection platforms (e.g., next-generation sequencing vs. digital PCR) remains a barrier to widespread clinical implementation. We conclude that integrating multianalyte liquid biopsies into clinical practice holds the potential to personalize therapeutic strategies, improve survival outcomes, and redefine the standard of care in head and neck oncology.
RNA-binding motif 47 (RBM47), a hub gene in atherosclerosis, induced oxidative stress in macrophages in atherosclerosis progression by enhancing ENC1 stability via binding to the AU-rich elements (AREs). However, RBM47 promoted C-to-U editing of multiple genes, such as acyl-CoA synthetase family member 2 (ACSF2), apoB, CD36, CD170, IL-10, oxysterol binding protein like 9, and transmembrane protein 30a (TMEM30A). These genes play important roles in atherosclerosis. Thus, the role of RBM47 in atherosclerosis may be complex. Notably, ACSF2 and HECT and RLD domain containing E3 ubiquitin protein ligase 2 promoted ferroptosis. TMEM30A exhibited a "don't eat me" signal. CD170 decreased ADAMTS13 activity. Recombinant ADAMTS-13 was undergoing phase 3 clinical trials. However, the biological significance of these genes after RNA editing, except for apoB and tight junction protein 1, is unclear. RBM47 also stabilized Axin1, Cullin 3, IL-8, Dickkopf WNT signaling pathway inhibitor 1, Kelch-like ECH-associated protein 1, and IL-10 expression by recognizing the GAUSAW (S = G/C, W = A/U) motif and AREs/GU-rich elements (GREs). However, the role of RBM47 in other genes that contain AREs and GREs, such as apoA-II, ABCA1, HMGCR, IFN-γ, IL-15, low-density lipoprotein receptor, oxidized low-density lipoprotein receptor 1, and programmed cell death 1 ligand 1, is unclear. This review focuses on the role and mechanism of RBM47-mediated genes in atherosclerosis to provide knowledge for new targets.
Chemoresistance constitutes a major cause of poor prognosis in advanced cervical cancer. Our previous studies have confirmed that Siglec-15 affects the progression of cervical cancer, whereas its role in regulating cervical cancer chemoresistance remains unexplored. This study investigates the role of Siglec-15 in cervical cancer chemoresistance and explores its mechanism. Siglec-15 expression and mitochondrial retrograde signaling levels were compared between parental and cisplatin-resistant cervical cancer cells. Lentiviral transfection was used to assess the functional effects of Siglec-15 modulation on the proliferation, apoptosis, and chemosensitivity of resistant cells. Further investigations were conducted to examine the effects of Siglec-15 on the mitogen-activated protein kinase (MAPK) signaling pathway, mitochondrial membrane potential, reactive oxygen species levels, and the expression of retrograde-related proteins. These in vitro findings were subsequently validated in vivo using a xenograft tumor model through immunohistochemistry, Terminal-deoxynucleotidyl transferase-mediated dUTP-nick-end labeling (TUNEL) assays, and western blotting. The results showed that Siglec-15 was markedly upregulated in cisplatin-resistant cervical cancer cells, correlating with enhanced mitochondrial retrograde signaling. Siglec-15 overexpression promoted cisplatin resistance and mitochondrial retrograde signaling, driving proliferation while inhibiting apoptosis. Mechanistically, Siglec-15 regulated mitochondrial retrograde signaling through activation of the MAPK pathway, thereby enhancing chemoresistance in drug-resistant cells. Elevated Siglec-15 expression enhances cisplatin resistance in cervical cancer cells by activating the MAPK pathway to promote mitochondrial retrograde signaling.
The purpose of this work was to examine the function of fibroblast growth factor 18 (FGF18) in rat myocardial ischemia-reperfusion injury (MIRI) and elucidate its relationship to mitochondrial function through the Sirtuin 1/peroxisome proliferator-activated receptor gamma coactivator 1 (SIRT1/PGC-1α) pathway. To evaluate myocardial infarct size, pathological alterations, cardiomyocyte injury, mitochondrial state, oxidative stress, and SIRT1/PGC-1α protein expression, FGF18-knockdown and FGF18-overexpression rat MIRI models were created. H9c2 cardiomyocytes were used to create an in vitro hypoxia-reoxygenation (H/R) model, and FGF18-overexpressing H9c2 cells were given the SIRT1 inhibitor EX-527. We detected the effects of FGF18-mediated regulation of the SIRT1/PGC-1α pathway on H/R-induced alterations in H9c2 cells, including cell viability, mitochondrial reactive oxygen species (ROS) production, mitochondrial membrane potential, apoptotic rate, and the protein expression of FGF18, SIRT1, PGC-1α, and mitofusin 1 (Mfn1). Furthermore, we performed a protein immunoprecipitation (IP)-protein acetylation assay to determine whether FGF18 influences the acetylation level of PGC-1α through the regulation of SIRT1. Results showed that FGF18 overexpression upregulated SIRT1/PGC-1α/Mfn1 expression, improved mitochondrial function, reduced oxidative stress, and enhanced H9c2 survival under H/R, while FGF18 knockdown had opposite effects. Moreover, FGF18 overexpression inhibited H/R-induced PGC-1α acetylation, and SIRT1 inhibition abrogated FGF18-mediated protective effects. Collectively, FGF18 attenuates rat myocardial MIRI by alleviating oxidative stress and regulating mitochondrial homeostasis through SIRT1-mediated deacetylation of PGC-1α.
Myocardial ischemia-induced cell injury involves the concurrent occurrence of pyroptosis, apoptosis, and oxidative stress, whereas its upstream regulatory mechanism remains unclear. The present study aimed to investigate the functional association between long noncoding RNA CRNDE and the NLRP3/ASC pathway in H9c2 cardiomyocytes subjected to hypoxia-induced injury. Using H9c2 cardiomyocytes as the research model, a hypoxia-induced injury model was constructed, shRNA-mediated knockdown of CRNDE was performed, and functional rescue experiments were conducted in combination with an NLRP3 agonist. Results showed that hypoxia treatment significantly upregulated the expression level of CRNDE in H9c2 cells, and this upregulation was significantly positively correlated with the activation of the NLRP3/ASC pathway. Knockdown of CRNDE specifically inhibited the mRNA and protein expression of key molecules in the NLRP3/ASC pathway (NLRP3, ASC, Caspase-1, GSDMD); reduced the secretion of inflammatory factors IL-1β and IL-18; decreased the cell apoptosis rate; and improved oxidative stress imbalance. RNA FISH assay confirmed that CRNDE was localized in the cytoplasm of H9c2 cells; knockdown of CRNDE alleviated hypoxia-induced mitochondrial damage, G1/S phase cell cycle arrest, and impairment of cell membrane integrity, and the above protective effects could be reversed by the NLRP3 agonist. In conclusion, CRNDE is closely associated with hypoxia-induced cardiomyocyte injury, and its effects in mediating pyroptosis, apoptosis, and oxidative stress rely on activation of the NLRP3/ASC pathway. Targeting CRNDE may provide a supplementary strategy for the treatment of myocardial ischemia-related diseases.
Idiopathic pulmonary fibrosis (IPF) is characterized by persistent fibroblast activation and progressive extracellular matrix remodeling, leading to irreversible lung architectural distortion. Although high-throughput omics approaches have advanced understanding of IPF pathogenesis, most studies have relied on single-omics analyses, limiting cross-layer functional interpretation. Here, we applied an integrated multi-omics strategy to characterize coordinated molecular alterations in IPF fibroblasts. Primary lung fibroblasts derived from patients with IPF and control subjects were analyzed using integrated transcriptomic, proteomic, and metabolomic profiling. Publicly available RNA-sequencing data deposited in the Gene Expression Omnibus (GEO; GSE301181) were used for transcriptomic analysis, while proteomic and metabolomic analyses were newly performed in a donor-matched subset of 10 IPF patients and 10 control subjects. Differentially expressed genes (DEGs), proteins (DEPs), and metabolites were identified using standardized statistical criteria, and cross-layer integration was conducted to identify molecules showing concordant regulation. Transcriptomic analysis identified 1,689 DEGs in IPF fibroblasts, whereas proteomic profiling initially quantified 6,236 proteins; after restricting analyses to peptide-supported proteins (≥2 unique peptides), 56 high-confidence DEPs were retained. Integration of transcriptomic and proteomic datasets identified 10 peptide-supported molecules exhibiting concordant regulation at both the mRNA and protein levels. Metabolomic profiling demonstrated significant reductions in metabolites involved in redox balance, lipid metabolism, glycolysis, nitrogen metabolism, and amine metabolism, indicating broad metabolic reprogramming associated with persistent fibroblast activation. Together, these findings suggest that IPF fibroblast activation is accompanied by coordinated transcriptional, translational, and metabolic reprogramming and highlight the value of integrated multi-omics analysis for interpreting regulatory features of fibrotic fibroblasts.
The mechanisms of Alzheimer's disease (AD) development are complex, and the detailed roles of neuroinflammation in AD still need to be elucidated. With various genetic and environmental risk factors, the accumulation of harmful amyloid plaques containing amyloid-β (Aβ) peptides is one of the main hallmarks of AD. Recent findings show that the innate immune protein interferon-induced transmembrane protein 3 (IFITM3) binds to γ-secretase and modulates Aβ production, providing a direct link between neuroinflammation, amyloidogenesis, and the pathogenesis of AD. In this review, we explore IFITM3-mediated modulation of γ-secretase complex activity and its pivotal role in AD pathology during neuroinflammation. Furthermore, we also provide an overview of the recent growing evidence connecting the roles of infection, the immune system, and AD pathogenesis.
Glycosylation, the enzymatic addition of sugar chains to proteins and lipids, is the most abundant and chemically diverse form of post-translational modification in eukaryotes. Despite its central role in cell biology, the glycosylation machinery has long been overlooked as a potential driver of cancer. By systematically mining large-scale cancer genomic datasets for somatic copy number alterations, we identified glycosyltransferases as a new class of oncogenic amplification targets. Here we discuss the biological rationale for why alterations in glycosyltransferase genes can drive oncogenesis, the role of the Golgi apparatus as the organizing hub of glycan biosynthesis, and the emerging therapeutic implications of these findings. Collectively, this evidence positions the glycosylation machinery not merely as a bystander altered in malignancy, but as an active and targetable driver of cancer.
X-ray repair cross-complementing protein 1 (XRCC1) protects cells from the effects of genotoxic stress by coordinating base excision repair (BER) and DNA single-strand break repair. XRCC1 phosphorylation and recruitment to sites of DNA damage are dependent on poly(ADP-ribose) polymerase-1 (PARP1) activity. As a central scaffolding protein, XRCC1 interacts with multiple components of BER pathway and also contributes to DNA double-strand break repair through the alternative nonhomologous end-joining pathway. In this regard, both established and recent studies have highlighted its critical role in spermatogenesis, extending beyond its classical association with PARP1. By integrating expression profiles with functional evidence, this review summarizes current insights into XRCC1 expression and subnuclear localization in spermatogenic cells, as well as its cooperative interaction with PARP1 in maintaining genomic integrity through efficient recombination and repair of genotoxic damage.
Lipid metabolism is abnormal in patients with atopic dermatitis (AD). This study aimed to screen lipid metabolism-related gene (LMRG) in AD, providing insights into the underlying mechanisms of lipid metabolism abnormalities in AD. Gene expression profiles from the Gene Expression Omnibus were analyzed to identify a hub LMRG in AD through an integrative approach combining weighted gene co-expression network analysis, differential expression analysis, and machine learning. The diagnostic value of the hub gene was assessed by receiver operating characteristic curve analysis. Its biological functions and associations with immune cells were investigated using Gene Set Enrichment Analysis (GSEA)/GSVA and ssGSEA/correlation analysis, respectively. The expression of ganglioside GM2 activator (GM2A) in clinical samples was measured using reverse transcription quantitative polymerase chain reaction and an ELISA assay. We identified 14 LMRGs that were differentially expressed between AD and normal samples and were correlated with AD onset. By three machine learning algorithms, GM2A was identified as a robust LMRG in AD. GM2A expression was observed to be elevated in AD samples across transcriptomic analyses and clinical validation. Moreover, GM2A might be effective in distinguishing between individuals with AD and those without. We further discovered that GM2A was associated with immunomodulation, inflammatory response, and biosynthesis of unsaturated fatty acid pathways. GM2A expression was positively correlated with follicular helper T cells, Activated CD4+ T cells, and natural killer T cells. Besides, there was a significant relationship between GM2A and multiple drugs. This study highlighted the significant up-regulation of GM2A as an efficient biomarker for AD, linking it to immune and inflammatory responses as well as immune cell infiltration.
Neurodegenerative diseases (NDDs) represent a growing global health burden, particularly in aging populations. These disorders primarily affect neurons and are characterized by progressive neuronal dysfunction and loss within specific regions of the central nervous system. Major NDDs include Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's disease, multiple sclerosis, and stroke. Although each disorder exhibits distinct genetic backgrounds and pathological protein aggregates, they share common pathogenic mechanisms, including chronic neuroinflammation, impaired autophagy and mitophagy, disrupted proteostasis, telomere instability, and epigenetic alterations. A hallmark feature across NDDs is the accumulation of misfolded proteins, leading to synaptic dysfunction and neuronal degeneration. Small ubiquitin-like modifiers (SUMOs) are a family of ∼100 amino acid proteins, including SUMO1 and the closely related SUMO2/3 isoforms. SUMOylation is a dynamic posttranslational modification that regulates protein function through the covalent attachment or removal of SUMO moieties. This reversible process is mediated by SUMO-specific E1 activating, E2 conjugating, and E3 ligating enzymes and is counterbalanced by SUMO/Sentrin-specific proteases. The SUMOylation status of target proteins depends on the tightly controlled balance between conjugation and deconjugation systems. Acting as a molecular switch, SUMOylation modulates diverse cellular processes such as DNA damage repair, RNA metabolism, transcriptional regulation, and protein quality control, all of which are essential for maintaining cellular homeostasis. Accumulating evidence links dysregulated SUMOylation to the pathogenesis of multiple neurological disorders, including polyglutamine and synucleinopathies. SUMOylation influences neuroinflammation, oxidative stress, protein aggregation, neuroangiogenesis, ischemic injury, and demyelination. This review highlights recent advances in understanding the role of SUMOylation in NDDs and explores its potential as a promising therapeutic target.
This study aims to investigate the expression of the SLC25 subfamily in sepsis-associated acute kidney injury (SA-AKI) and the role of SLC25A30 in regulating PINK1/PARKIN-mediated mitophagy. Transcriptome sequencing of renal tissues from lipopolysaccharide (LPS)-induced SA-AKI rats at multiple time points revealed time-dependent differential expression of SLC25 genes. At 12 h post-LPS injection (renal injury peak), 11 differentially expressed genes were identified. Intersection with Gene Expression Omnibus datasets and Gene Ontology enrichment highlighted 11 codifferentially expressed genes enriched in mitochondrial transmembrane transport. Notably, SLC25A30 was significantly negatively correlated with KIM-1 (r = -0.96) and LCN2 (r = -0.98). SLC25A30 was significantly downregulated in SA-AKI rat renal tissues and LPS-induced HK-2 cells, accompanied by upregulated PINK1/PARKIN, excessive mitophagy (elevated LC3B-II, decreased p62), and increased renal injury markers. SLC25A30 overexpression inhibited PINK1/PARKIN, reversed excessive mitophagy, reduced KIM-1 and LCN2 levels, alleviated mitochondrial dysfunction, enhanced cell viability, and exerted cytoprotective effects. PINK1 knockdown attenuated the regulatory effect of SLC25A30 on excessive mitophagy, indicating a dependence on the PINK1/PARKIN pathway. In conclusion, downregulated SLC25A30 is closely associated with excessive mitophagy in SA-AKI. SLC25A30 overexpression inhibits excessive mitophagy via downregulating the PINK1/PARKIN pathway, improves mitochondrial function, and alleviates HK-2 cell injury, suggesting that SLC25A30 may be a novel molecular target for SA-AKI-targeted therapy.
This study investigated the influence of homeopathic medicines (HMs) on the in vitro behavior of stem cells from human exfoliated deciduous teeth (SHED). The HMs Symphytum officinale (SO), Calcarea carbonica (CC), and Calcarea phosphorica (CP) were evaluated, along with a vehicle control (V), using cells from a single donor in passages 4 (P4) and 5 (P5). Cellular responses were assessed using Neutral Red (viability-related activity), Crystal Violet (adherent cell density), MTT (metabolic activity), and scanning electron microscopy (SEM). Across assays, consistent modulation of cellular behavior was observed, particularly in P5 at 72 h. Neutral Red uptake increased over time in P4 and showed treatment-dependent responses in P5. Crystal Violet indicated increased adherent cell density, with higher values in P5 compared to P4. MTT demonstrated increased metabolic activity at 72 h, especially in P5. SEM analysis confirmed these findings, showing that cells treated with SO, CC, and CP remained well adhered and spread, with increased cell density and more compact organization. In contrast, the vehicle group exhibited reduced cell density and altered morphology. Overall, the tested HMs were associated with measurable changes in SHED behavior without evident adverse effects. These findings should be interpreted as exploratory and require further validation.
Liver fibrosis (LF) is a fibrotic and inflammatory condition resulting from chronic liver damage, and the activation of hepatic stellate cells (HSCs) is the central event. Our prior research has revealed that the circAno6/miR-296-3p/Toll-like receptor (TLR4) pathway is a key signaling axis in the pathogenesis of LF. Shugan Jianpi Formula (SGJPF) is a traditional Chinese medicinal treatment widely used to treat LF. We hypothesized that SGJPF exerts anti-LF effects by modulating the circAno6/miR-296-3p/TLR4 signaling axis, attenuating inflammatory responses, and inhibiting HSC activation, thereby ultimately mitigating LF. In this study, an SGJPF extraction solution was first prepared and administered to rats via gavage at a specified dosage. Blood samples were subsequently collected from the abdominal aorta to prepare SGJPF-containing serum. Optimal SGJPF intervention conditions were determined using the Cell Counting Kit-8 assay. Flow cytometry was used to assess JS-1 cell cycle progression. The levels of interleukin-1 beta (IL-1β) and IL-18 were measured by enzyme-linked immunosorbent assay. The expression levels of collagen type I (collagen I), α-smooth muscle actin (α-SMA), circAno6, TLR4, miR-296-3p, and NOD-like receptor protein 3 (NLRP3) were evaluated using Western blotting, immunofluorescence, and real-time quantitative polymerase chain reaction. The results indicated that the optimal intervention condition involved serum containing 20% SGJPF, which was administered for a duration of 48 h. SGJPF-containing serum has been shown to reduce the viability of JS-1 cells and decrease the cell count in the G2 + S phase, thereby affecting HSC function. Furthermore, SGJPF-containing serum effectively suppressed the expression levels of NLRP3, IL-1β, IL-18, collagen I, α-SMA, circAno6, and TLR4 while upregulating miR-296-3p expression. These findings suggest that SGJPF can modulate the activity of the circAno6/miR-296-3p/TLR4 signaling axis, attenuate inflammatory responses, and inhibit HSC activation, thereby mitigating LF.
Dent disease 1, an X-linked recessive proximal tubulopathy most commonly caused by CLCN5 variants, often presents with heterogeneous and nonspecific phenotypes that hinder clinical diagnosis in the absence of molecular data. We investigated a Chinese kindred with suspected hereditary renal disease using whole-exome sequencing and comprehensive in silico analyses and identified a novel frameshift variant in CLCN5 (NM_001127899: c.2359dupG/p.R788Afs*24). Segregation analysis showed the proband to be hemizygous, with his mother and daughter as heterozygous carriers. Pathogenicity prediction, domain mapping against published CLCN5 variants, and literature review indicate that this variant lies within a functionally critical, variant-hotspot region of the protein where truncating variants correlate with classic Dent disease 1 phenotypes. Molecular docking and structural modeling further predict destabilization of the H+/Cl- exchange transporter 5 (CLC-5) dimer and reduced adenosine triphosphate (ATP)/adenosine diphosphate (ADP) binding affinity attributable to the frameshift, providing mechanistic plausibility for impaired channel function. Collectively, genetic, bioinformatic, and structural evidence support the p.R788Afs24 mutant as a likely pathogenic allele underlying the proband's renal phenotype, expanding the variant spectrum of CLCN5 and underscoring the necessity of genetic testing for accurate diagnosis and management of Dent disease 1.
Isocitrate dehydrogenase (IDH)-mutant gliomas are primary malignant brain tumors defined by recurrent mutations in IDH1/2 genes and characterized by distinct molecular subtypes and relatively favorable clinical outcomes. Although these mutations represent early and defining events, recent data suggest that IDH1 mutant glial progenitor cells can reside within the histologically normal-appearing peritumoral cortex, indicating that cells harboring the founding driver mutation can persist beyond the tumor mass while retaining nonmalignant features. These observations challenge a purely gene-centric view of gliomagenesis. In this essay, we review emerging data supporting a multistep and context-dependent model in which the mutant IDH enzyme establishes an epigenetically altered cellular state, with subsequent genetic alterations and lineage-specific constraints that shape malignant progression. We further discuss the conceptual distinction between the "cell-of-mutation" and the "cell-of-origin" and consider how temporal stratification of tumor evolution may inform stage-specific therapeutic strategies along the transition from initiating clones beyond the tumor mass to overt tumors.
Cyclin-dependent kinase 17 (CDK17) is an understudied member of the PCTAIRE family of CDKs, with phosphorylation-guided molecular mechanism being underexplored. In this study, an in-depth mass spectrometry-based phosphoproteomics data integration and harmonization, coupled with replicable statistical analysis, was performed to understand the phosphorylation landscape of CDK17. High-confidence phosphorylation sites of CDK17 were derived from 711 phosphoproteomics profiling studies, where 176 datasets showed differential phosphorylation of CDK17. Among 13 identified phosphorylation sites of CDK17, S180, S137, and S146 were prominently detected in 75% of all the datasets. Notably, sequence conservation of CDK17 (S146, S137, and S180) with CDK16 (S119, S110, and S153) and CDK18 (S98, S89, and S132), respectively, was observed, where CDK16 (S119) is a part of the binding motif for multiple upstream kinases, 14-3-3 protein, and CCNYL1. Furthermore, conserved co-regulatory patterns of other proteins were identified as compared with CDK17 phosphorylation, which revealed 19 upstream kinases, 164 downstream substrates, and several interactors of CDK17, which conserved co-regulatory patterns across diverse biological contexts. Statistical analysis revealed phosphoregulation of CDK17 through other kinases, regulation of CDK17 substrates, protein-protein interactions, and conserved co-differential regulation in multiple datasets. Specifically, this analysis derived through global data integration with a replicable analytical framework lays a groundwork for experimental validation of CDK17 phosphorylation in its functional regulation.
Liensinine (LIE), a bioactive alkaloid from Nelumbo nucifera, exhibits proapoptotic and anticancer properties. Its effect and mechanism in pancreatic cancer remain unexplored, representing a novel research direction. We employed an integrated strategy combining network pharmacology, transcriptome sequencing, and experimental validation to investigate LIE's action against PANC-1 pancreatic cancer cells. Key targets and pathways were identified via bioinformatics analyses. Molecular docking and survival analysis were conducted to verify core targets. In vitro assays including CCK-8, lactate dehydrogenase release, Hoechst/PI staining, flow cytometry, wound healing, and transwell invasion were used to assess cytotoxicity, apoptosis, migration, and invasion. Western blotting validated protein-level changes. Network pharmacology revealed 90 overlapping targets of LIE and pancreatic cancer, with the Phosphatidylinositol 3-k (PI3K)/Serine/Threonine Kinase (AKT) pathway being significantly enriched. Molecular docking indicated a strong binding affinity of LIE to Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Alpha (PIK3CA) and AKT1. Survival analysis associated high PIK3CA expression with poorer prognosis in pancreatic cancer patients. In vitro, LIE dose-dependently inhibited PANC-1 cell proliferation, migration, and invasion while significantly inducing apoptosis. Western blotting confirmed that LIE treatment effectively suppressed the activation of the PI3K/AKT signaling pathway. Our study is the first to demonstrate that LIE exerts potent antitumor effects against pancreatic cancer cells by inducing apoptosis and inhibiting malignant phenotypes through suppression of the PI3K/AKT pathway. These findings highlight LIE as a promising novel therapeutic candidate for pancreatic cancer treatment.
Bacteriophages (phages) are viruses that specifically infect bacteria and play a central role in shaping microbial communities and bacterial evolution. Beyond their protein-coding genes, phage genomes were found recently to encode small RNAs (sRNAs) that act post-transcriptionally to regulate host and viral gene expression. These phage-encoded sRNAs can influence infection dynamics, modulate host physiology, and determine the balance between lytic and lysogenic cycles. A prominent example is the phage lambda sRNA PreS, which enhances phage DNA replication by increasing translation of the host dnaN mRNA, linking host replication capacity to phage propagation. This review examines emerging evidence that phage-encoded sRNAs constitute a versatile and underappreciated class of molecular tools. We discuss how such RNAs could be repurposed as precision antibacterial agents in an era of increasing antibiotic resistance and outline key challenges and opportunities for developing RNA-based alternatives to conventional phage therapy.
Breast cancer is the most diagnosed cancer in women and the second leading cause of cancer-related mortality worldwide. Advances in genetic technology have highlighted the heterogeneity of breast cancer, composed of various biological subtypes, with genetic profiling playing a crucial role in predicting chemotherapy response. This underscores the importance of identifying sensitive diagnostic and prognostic markers for early detection and developing more efficient targeted therapies. Among these, survivin, a protein linked to apoptosis inhibition and cell cycle regulation, is strongly expressed in various cancers, including breast cancer, where its overexpression is associated with poor prognosis and reduced survival rates. To analyze the effects of survivin gene inhibition in a triple-negative breast cancer (TNBC) model. The MDA-MB-231 cell line was stably transfected with short hairpin RNA targeting survivin, and the inhibition was validated via RT-qPCR and Western blot. Morphological evaluation, proliferation and migration assays, and a differential gene expression analysis using the GeneChip™ Human Gene 2.0 ST Array were performed. Statistical analyses were conducted with GraphPad Prism version 8 and Transcriptome Analysis Console. Survivin-inhibited MDA-MB-231-KD cells exhibited evident morphological changes, reduced migration capacity, and altered expression of genes such as BCL2, COX1, COX2, VGF, BIR2, and CDC20, involved in key cancer signaling pathways. Inhibition of survivin in this TNBC model induces critical cellular changes and significantly alters gene expression associated with tumor progression, highlighting its potential as a therapeutic target.
