DNA and cell biology最新文献

Mitochondria, originating from symbiotic ancestors, are acknowledged as the powerhouses of the cell. Their relevance to various cancer types is underscored by altered glucose metabolism (Warburg effect). Mitochondrial DNA (mtDNA) plays a crucial role in oxidative damage and is a significant contributor to cancer onset and progression. Tobacco and alcohol consumption increases reactive oxygen species generation, inducing oxidative stress that disrupts respiratory activity and mtDNA, thereby promoting carcinogenesis. This review emphasizes the link between mitochondrial dysfunction and cancer, particularly in oral squamous cell carcinoma (OSCC), highlighting the role of mtDNA mutations. This review discusses environmental factors, such as tobacco use and human papillomavirus infection, that impact mitochondrial function, stresses the importance of mitochondrial-targeted therapies, and explores the influence of microRNAs (miRNAs) on mitochondrial metabolism in cancer cells. Mitocans and miRNAs have emerged as promising therapeutic agents for OSCC. The subsequent sections delve into recent pivotal research on mitochondria, identifying mtDNA alterations as potential cancer biomarkers. These insights promise new perspectives on noninvasive cancer detection, heralding advancements in cancer therapeutics.

Cuproptosis is a regulated cell death mechanism that has recently been identified and is distinct from other known cell death mechanisms (e.g., apoptosis, Ferroptosis, necrotic apoptosis, etc.). Cuproptosis causes oligomer formation through the abnormal accumulation of intracellular copper ions that target binding to lipocytosed proteins, especially those involved in the tricarboxylic acid cycle. At the same time, it can destabilize iron-containing sulfur proteins, thereby inducing proteotoxic stress, leading to triggered cell death. It has also been shown that cuproptosis is also associated with oxidative stress activation and inhibition of the ubiquitin-proteasome system. Genes linked to cuproptosis were screened, and knocking out seven genes reversed cuproptosis: reductase-ferredoxin 1; the three genes of the lipoic acid pathway-lipoyltransferase 1, lipoyl synthase, and dihydrolipoamide dehydrogenase; and the acylated protein targets-dihydrolipoyl transacetylase (DLAT), pyruvate dehydrogenase complex component A1 (PDHA1), and pyruvate dehydrogenase complex component B (PDHB). Among them, the β subunit of pyruvate dehydrogenase, encoded by the PDHB gene, can form a tetramer with the α subunit and irreversibly catalyze the physiological function of converting pyruvate to acetyl-CoA since DLAT provides structural support and also exhibits enzymatic activity within the pyruvate dehydrogenase complex (PDC). Furthermore, within the PDC, the primary target of cuproptosis is DLAT rather than PDHB or PDHA1. Consequently, the involvement of PDHB in the inactivation of PDC caused by cuproptosis is more likely a secondary consequence. In this review, the characteristics of the cuproptosis-associated gene PDHB and its role in the biological function and pathogenesis of the disease are discussed.

N⁶-Methyladenosine (m⁶A) is a reversible RNA modification that regulates tumorigenesis. KIAA1429, a critical component of the m⁶A methyltransferase complex, has an unclear role in clear cell renal cell carcinoma (ccRCC). Here, we investigated the role of KIAA1429 in ccRCC tumorigenesis. The expressions of KIAA1429 and thymosin beta-10 (TMSB10) in ccRCC samples were evaluated using quantitative real-time PCR (qRT-PCR). The malignant features of ccRCC cells were assessed via CCK-8, colony formation, transwell migration, and invasion assays, as well as in vivo tumor xenograft models. The relationship between KIAA1429 and TMSB10 was verified via Pearson correlation analysis, methylated RNA immunoprecipitation, qRT-PCR, and Western blotting assays. Functional rescue experiments further confirmed their interaction. We found that KIAA1429 was highly expressed in ccRCC, and its silencing significantly suppressed cell proliferation, migration, invasion, and tumor growth in vivo, while overexpression had the opposite effect. Bioinformatics and mechanistic analyses identified TMSB10 as a downstream target of KIAA1429, whose expression was upregulated in an m⁶A-dependent manner. Furthermore, overexpressing TMSB10 partially reversed the inhibitory effects of KIAA1429 silencing on ccRCC cells. Moreover, TMSB10 overexpression partially reversed the inhibitory effects of KIAA1429 knockdown. Taken together, our findings demonstrate that KIAA1429 promotes ccRCC tumorigenesis by enhancing TMSB10 expression via m⁶A modification, suggesting it as a potential prognostic biomarker and therapeutic target. However, the lack of clinical validation limits the immediate translational impact of these findings.

The 6-methyladenine (m6A) modification plays a major role in various diseases. Serine protease 8 (Prss8) contributes to the initiation and progression of liver fibrosis (LF). However, the mechanism by which the m6A modification of Prss8 induces hepatic stellate cells (HSCs) activation in the LF is unclear. This study focused on exploring the contribution of Prss8 m6A modification to the pathogenesis of LF. First, primary hepatic parenchymal cells (hepatocytes) and HSCs were isolated from a mouse model of LF, and a coculture of these two types of cells was used as the object of study. Then, real-time fluorescence quantitative PCR, methylated RNA immunoprecipitation, and Western blotting were used to test the expression levels of Prss8 mRNA and protein, Prss8 m6A modification, Collagen I, α-SMA, and TLR4. Finally, the expression levels of inflammatory markers were measured via an enzyme-linked immunosorbent assay. Compared with the control group, the model group presented significantly lower Prss8 mRNA and protein levels in hepatocytes but greater levels of Prss8 m6A modification; moreover, the expression of HSC activation markers and the TLR4, IL-1β, and IL-18 proteins was significantly elevated. Mutation of the Prss8 m6A modification site led to upregulation of Prss8 mRNA and protein and decreased levels of m6A modification, TLR4, IL-1β, and IL-18. Furthermore, mutation of the Prss8 m6A modification site increased the stability of Prss8 mRNA. Rescue experiments confirmed the regulatory link between Prss8 m6A modification and TLR4. Overall, Prss8 m6A modification decreases the stability of its mRNA, promoting TLR4-mediated inflammatory cascades and leading to excessive activation of HSCs. Targeting Prss8 m6A modification is a promising therapeutic strategy for LF.

The exosome-mediated circular RNAs (circRNAs) play a crucial role in tumorigenesis. The present study investigated the role of the exosome-mediated circRNA hsa_circ_0113050 in colorectal cancer (CRC) through its interaction with the eukaryotic translation initiation factor 4A3 (EIF4A3). CRC-derived exosomes were isolated and characterized by differential ultracentrifugation, transmission electron microscopy, and nanoparticle tracking analysis. The hsa_circ_0113050 expressions in CRC and exosomes were confirmed through a bioinformatic analysis and quantitative reverse transcription-polymerase chain reaction (qRT-PCR) assays. Cell functional and in vivo assays were applied to evaluate the effects of exosomes and hsa_circ_0113050 on CRC cell malignancy. The interaction between EIF4A3 and hsa_circ_0113050 was analyzed by RNA immunoprecipitation, Western blotting, and qRT-PCR assays. CRC-derived exosomes with diameters of 102 and 104 nm enhanced the ability of CRC cells to proliferate, migrate, and invade. hsa_circ_0113050 was highly expressed in CRC tissues and CRC-derived exosomes. Silencing hsa_circ_0113050 in exosomes effectively reversed the exosome-induced CRC cell malignancy. Furthermore, EIF4A3 bound to the linear gene (EIF3I) of hsa_circ_0113050 to enhance the hsa_circ_0113050 expression in the CRC cells. In conclusion, the present study is the first to reveal that exosome-mediated hsa_circ_0113050 enhances CRC cell malignancy by interacting with EIF4A3. Our study findings provide new mechanistic insights into circRNA regulation and highlight a potential therapeutic target for CRC.

Bile acids (BAs) have garnered significant attention due to their novel roles in modulating diverse host physiological processes. They play a crucial role in nutrient transport, organelle function, and maintaining the systemic balance of pro/anti-inflammatory states. BAs exert complex physiological effects through their interaction with nuclear receptors, such as farnesoid X receptor or cell membrane receptor Takeda G protein-coupled receptor 5. Disruption of BA transport and homeostasis results in the accumulation of BAs and elevated concentrations in the systemic circulation. This contributes to the pathogenesis of cholestatic disorders and is implicated in a variety of liver diseases, including primary biliary cholangitis and primary sclerosing cholangitis. In the context of cholestatic liver injury, BAs interact with parenchymal hepatocytes and nonparenchymal cells, leading to hepatocyte apoptosis, activation of hepatic stellate cells, and the initiation of inflammatory responses. Identifying key cellular and molecular components involved in this interaction may contribute to the development of potential therapies for cholestatic liver diseases. In this article, we provide a summary of the molecular mechanisms underlying BA-mediated interactions with various cell types in the cholestatic liver and discuss therapeutic strategies targeting BA pathways. We anticipate that a deeper understanding of these interactions will enable the formulation of novel strategies for the treatment of cholestatic liver injury.

Mitochondrial cardiomyopathy is a rare specific myocardial condition characterized by abnormal myocardium structure and/or function due to mitochondrial respiratory chain deficiency. This cardiac disorder results from mutations in mitochondrial DNA or nuclear genes affecting mitochondrial function. These mutations disrupt oxidative phosphorylation and consequently lead to energy deficit in the myocardial tissue and systemic symptoms due to impaired mitochondrial metabolism. In the current review, we aimed to highlight genetic and molecular underpinnings of mitochondrial cardiomyopathy. The impact of mitochondrial DNA characteristics on mitochondrial cardiomyopathy, mutations in both mitochondrial and nuclear genomes, as well as diagnostic limitations and future therapies, will be presented in this work.

Regenerating periodontal tissues remains a significant hurdle in regenerative dentistry, requiring meticulous coordination of cellular and molecular mechanisms. Noncoding RNAs (ncRNAs), including microRNAs, long ncRNAs, and circular RNAs, are emerging as essential modulators of bone morphogenetic protein (BMP) signaling pathways, which are vital for processes such as osteogenesis, cementum formation, and periodontal ligament (PDL) repair. This review delves into the pivotal role of ncRNAs in influencing BMP signaling while briefly addressing their interaction with other critical pathways, such as transforming growth factor-beta, Activin, Wnt, Notch, mitogen-activated protein kinase, and PI3K. These ncRNAs act as dynamic regulators, fine-tuning BMP signaling to facilitate tissue differentiation, modulate inflammatory responses, and enhance extracellular matrix remodeling-key elements for addressing the complexity of periodontal tissue regeneration. By compiling the latest advancements, this review sheds light on the potential of ncRNAs as therapeutic targets, emphasizing their ability to refine BMP signaling for greater precision in tissue engineering. Moreover, the integration of ncRNA insights with advanced biomaterials and engineering solutions offers a promising direction for reconstructing the intricate bone-PDL-cementum complex. Framing ncRNAs as a central innovation in regenerative therapy, this review underscores their transformative potential in addressing the multifactorial challenges of periodontal repair and restoration.

The increasing use of silver nanoparticles (AgNPs) in aquaculture has raised concerns regarding their potential toxic effects on fish health, particularly on vital organs, such as the liver and kidneys. Licorice (Glycyrrhiza glabra) root, known for its medicinal and antioxidant properties, has gained attention as a natural agent capable of mitigating such toxicity. Furthermore, licorice extract can be used in the eco-friendly green synthesis of AgNPs, acting as both a reducing and stabilizing agent, as confirmed by characterization techniques including X-ray diffraction, Fourier-transform infrared spectroscopy, and transmission electron microscopy. This study aimed to evaluate the protective effects of dietary licorice root powder against AgNP-induced histopathological and physiological damage in common carp (Cyprinus carpio). A total of 150 fish were randomly assigned to seven dietary treatment groups for 56 days, including a control group, three groups receiving increasing doses of AgNPs (2.5, 5, and 7.5 mg/kg feed), and three groups receiving corresponding combinations of same amount of AgNPs with licorice root powder (2.5, 5, and 7.5 g/kg feed). Histopathological evaluation revealed that AgNPs alone induced severe liver and kidney damage, including hydropic degeneration, necrosis, and inflammatory infiltration. In contrast, fish receiving licorice-supplemented diets showed significantly reduced tissue lesions, indicating hepatoprotective and nephroprotective effects. In conclusion, licorice root powder effectively mitigated AgNP-induced toxicity and improved organ health in common carp. The combination of licorice and AgNPs offers a promising alternative to antibiotics in aquaculture, enhancing sustainability and fish welfare. Further studies are recommended to investigate the underlying molecular mechanisms and optimize application strategies in fish diets and to investigate another model of animal.