Molecular medicine reports最新文献

As the first functional organ to form during vertebrate embryogenesis, the heart exhibits heightened susceptibility to developmental toxicity. Epigenetic regulatory mechanisms, including DNA methylation, histone modifications, non‑coding RNAs, N6‑methyladenosine methylation and chromatin accessibility alterations, mediate cardiac developmental toxicity induced by exogenous compounds including environmental chemicals and pharmaceuticals. The present review comprehensively summarizes the current understanding of the molecular mechanisms through which these compounds exert cardiac developmental toxicity through epigenetic regulation. An in‑depth analysis of research progress and technical challenges across diverse epigenetic pathways is provided. By summarizing recent evidence, the present review proposes candidate epigenetic biomarkers for cardiac developmental toxicity monitoring and explores potential intervention strategies targeting these pathways. Future research should prioritize multi‑omics integration technologies and clinical translation system development. These advances are anticipated to foster innovation in both mechanistic research and preventive strategy development for cardiac developmental toxicity.

Following the publication of the above paper, a concerned reader drew to the Editor's attention that, within the left‑hand and centre data panels of Fig. 6 on p. 5735, apparent anomalies were identifiable, including unexpectedly similar‑looking cells and repeated patternings of these cells in terms of their layout/arrangement, albeit with inversions of the cells in certain cases. In addition, it was noted that some of the data featured in Table I and in Fig. 4B were strikingly similar to data that had previously appeared in a paper published in the journal Cell Biochemistry and Biophysics that was written by different authors at different research institutes. After having conducted an independent investigation of this paper in the Editorial Office, the Editor of Molecular Medicine Reports has determined that it should be retracted from the Journal on account of a lack of confidence in the authenticity of the data. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor regrets any inconvenience that has been caused to the readership of the Journal. [Molecular Medicine Reports 12: 5730‑5736, 2015; DOI: 10.3892/mmr.2015.4169].

Recurrence and metastasis are the leading causes of poor prognosis and death in lung cancer, and the mechanism of cancer metastasis has not yet been fully elucidated. As a gut-specific homeobox (HOX) transcription factor, intestine-specific HOX (ISX) is a proto-oncogene induced by the inflammatory factor IL-6. Notably, ISX overexpression can induce the epithelial-mesenchymal transition (EMT) response, and promotes tumor cell migration and invasion. In the present study, a lung cancer cell model with overexpression of ISX was established by infecting lung cancer cells with lentivirus. Reverse transcription-quantitative polymerase chain reaction was first used to verify the expression of the EMT-related gene induced by ISX overexpression. Furthermore, transcriptome sequencing and analysis showed that the overexpression of ISX induced significant changes in the gene expression profile of human lung cancer cells. In addition, type I collagen α1 chain (COL1A1), a highly expressed gene in various tumor tissues and cells, was shown to promote tumor cell migration and invasion, possibly by promoting EMT, and was significantly upregulated in human lung cancer cells overexpressing ISX. These results suggested that ISX may promote lung cancer migration and invasion by increasing the expression of COL1A1. In addition, four drugs that are currently used to treat lung cancer were screened. Of these, Iressa® (gefitinib) was revealed to significantly inhibit the viability, migration and invasion of lung cancer cells that stably overexpress ISX by downregulating the expression of COL1A1. In conclusion, these findings may help to prevent tumor metastasis and spread, and the potential molecular mechanism by which ISX promotes the development and migration of lung cancer was suggested. The current findings provide novel targets, and a scientific basis for the prevention and treatment of lung cancer, which may reduce costs for patients, their families and society.

Infantile hemangioma (IH), a common vascular tumor, occurs in childhood; however, its pathogenesis has not been fully elucidated. In the present study, the roles and detailed mechanisms of long non‑coding RNA (lncRNA) NEAT1 in the progression of hemangioma were further explored. The NEAT1‑interacting proteins were selected by analyzing the catRAPID database and lactate dehydrogenase B (LDHB) was predicted to bind with NEAT1. The binding between NEAT1 and LDHB was validated using an RNA immunoprecipitation assay and it was further found that knocking down NEAT1 expression destabilized LDHB by regulating the proteasome pathway. The knocking down of lncRNA NEAT1 also inhibited cellular protein lactylation and downregulated β‑catenin. Furthermore, blockade of lactylation via 2‑DG and oxamate attenuated the viability and colony formation of hemangioma cells. NEAT1 promoted the lactylation of H3K18 in the promoter region of β‑catenin, and blockade of lactylation downregulated β‑catenin expression in hemangioma cells. The lactyltransferases alanyl‑tRNA synthetase 1 and P300 were regulated by NEAT1 and also positively regulated β‑catenin. The levels of β‑catenin mRNA and H3K18 lactylation were also found to be elevated in IH tissues. Taken together, the results of the present study revealed that lncRNA NEAT1, which is upregulated in hemangioma, binds with and stabilizes LDHB, subsequently elevates the levels of cellular lactate and H3K18 lactylation, potentiates β‑catenin transcription and ultimately enhances the proliferation of hemangioma cells.

Subsequently to the publication of this paper, an interested reader drew to the authors' attention that, in the "Identification of hub genes for CRC" subsection of the Results on p. 8263, the left‑hand column, in the first sentence the reference to Matthew's correlation coefficient algorithm should perhaps have been written as the Maximal Clique Centrality algorithm. The authors have replied to confirm that, upon carefully reviewing the paper, the Maximal Clique Centrality algorithm from the CytoHubba plugin was indeed used to identify the top 20 hub genes, and that, during the manuscript preparation, the full name of "MCC" was incorrectly written as "Matthews correlation coefficient" due to an oversight on their part. Therefore, the first sentence in this subsection of the Results section should have read as follows: "To identify potential hub genes among the 306 genes previously identified, the Maximal Clique Centrality (MCC) algorithm from the CytoHubba software plug‑in was used." The authors sincerely apologize for any confusion or misunderstanding this error may have caused for the readers, and are grateful to the Editor of Molecular Medicine Reports for granting them the opportunity to publish this corrigendum. [Molecular Medicine Reports 17: 8260‑8268, 2018; DOI: 10.3892/mmr.2018.8862].

Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that certain of the cell apoptotic data shown in Fig. 5A were strikingly similar to data appearing in different form in another article written by different authors at different research institutes that had already been published in the journal Cell Cycle; moreover, the lens smudging patterns underlying the neurite outgrowth experimental data shown in Figs. 2D and 5C matched that of data shown in other figures of the same article published in journal Cell Cycle, suggesting these data may have been derived from the same original source. Owing to the fact that the contentious data mentioned above had already apparently been published previously, the Editor of Molecular Medicine Reports has decided that this paper should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [Molecular Medicine Reports 22: 1489‑1497, 2020; DOI: 10.3892/mmr.2020.11203].

The pathogenesis of inflammatory bowel disease is associated with dysfunction of the intestinal mucosal barrier. Protein sialylation serves an important role in maintaining the integrity of this barrier. The present study investigated how α2,3‑linked sialylation catalyzed by protein ST3Gal1 affected intestinal barrier function and impacted the pathogenesis of human ulcerative colitis (UC). The present study employed Caco‑2, HT29‑MTX‑E12 and THP‑1 cells with distinct functionalities to establish an in vitro triple‑culture model. This model was utilized to simulate both healthy and inflamed states of the human intestine for investigating the impact of ST3Gal1‑mediated α2,3‑sialylation on the integrity of the intestinal barrier. The triple‑culture model was stably infected with adenoviral particles or lentiviral vectors to establish ST3Gal1 knockdown and overexpression, respectively, followed by isolation through incubation with 4 µg/ml puromycin. The functionality of the intestinal barrier was assessed via trans‑epithelial electrical resistance and FITC‑dextran permeability assays. ST3Gal1 expression was found to be associated with inflammation of the intestinal mucosa in patients with UC and a mouse model of dextran sulfate sodium‑induced colitis. Notably, suppressed expression of ST3Gal1 in the intestinal epithelial cell (IEC) monolayer enhanced the functionality of the intestinal barrier, whereas its overexpression caused intestinal barrier function deterioration. ST3Gal1 expression in the IEC monolayer altered the expression of intestinal mucus barrier‑associated mucin 2 (MUC2) and trefoil factor 3 (TFF3), goblet cell differentiation‑associated homeobox protein CDX‑2 (CDX2), inflammation‑associated phosphorylated (p)‑STAT3, and the inflammatory mediators IL‑1β, IL‑6 and IL‑8. Specifically, MUC2, TFF3 and CDX2 were positively associated with enhanced barrier integrity, whereas p‑STAT3, IL‑1β, IL‑6 and IL‑8 were negatively correlated with barrier function. Collectively, these results demonstrated a strong association between these factors and the regulation of intestinal barrier function. In conclusion, ST3Gal1‑catalyzed α2,3‑linkage formation in IECs may be closely associated with intestinal barrier function via its effect on the expression of barrier‑associated proteins and inflammatory mediators related to intestinal mucosa inflammation.

Proliferative vitreoretinopathy (PVR), a leading complication of retinal detachment with high recurrence rates and no effective pharmacological treatments, is driven by retinal pigment epithelium (RPE) cells through epithelial‑mesenchymal transition (EMT), a process promoted by methyl‑CpG binding protein 2 (MeCP2). There is bidirectional crosstalk between ferroptosis, an iron‑dependent cell death pathway characterized by lipid peroxidation and EMT, suggesting their interaction may influence PVR pathogenesis. However, the mechanistic involvement of ferroptosis in PVR and its interaction with the MeCP2/EMT axis remain poorly understood. In the present study, a scratch assay demonstrated that MeCP2 enhanced ARPE‑19 cell migration, which was markedly suppressed by erastin. Cell Counting Kit‑8 assays and western blot analysis confirmed that Erastin inhibited cell proliferation without triggering apoptosis. Western blotting and corresponding assay kits both revealed that MeCP2 upregulated glutathione peroxidase 4 (GPX4), glutamate‑cysteine ligase modifier subunit and solute carrier family 7 member 11, increased glutathione levels and decreased malondialdehyde and Fe²⁺ concentrations, indicating ferroptosis suppression. Erastin reversed EMT by reducing fibronectin (FN) and α‑smooth muscle actin (α‑SMA) expression and restoring E‑cadherin, as shown by western blotting. Further investigation revealed that GPX4 activation exacerbated EMT marker expression (FN, α‑SMA and N‑cadherin), while GPX4 inhibition mitigated these effects, confirming that MeCP2 regulates EMT through GPX4‑dependent ferroptosis. Erastin inhibited MeCP2‑driven ARPE‑19 proliferation, migration and EMT via ferroptosis induction, independent of apoptosis. MeCP2 suppressed ferroptosis through GPX4 upregulation, using this pathway to orchestrate EMT, thus revealing a critical GPX4‑dependent mechanism that links ferroptosis to RPE plasticity in PVR. These findings highlighted ferroptosis modulation as a promising therapeutic strategy for PVR.

R‑loops, three‑stranded nucleic acid structures composed of an RNA:DNA hybrid and displaced single‑stranded DNA, have emerged as important regulators of gene expression and genome maintenance. Although physiological R‑loops participate in normal cellular processes, their dysregulation can threaten genomic integrity by inducing DNA damage and replication stress. The present review explores the role of R‑loops in hepatocellular carcinoma (HCC), a malignancy characterized by marked genomic instability. In the present review, the formation mechanisms of R‑loops, their dual functions in transcriptional regulation and DNA damage, and their specific implications for HCC pathophysiology were discussed. HCC cells exhibit altered R‑loop homeostasis with aberrant accumulation linked to hepatitis B virus infection, inflammatory signaling and oncogene activation. The present review highlighted how HCC cells exploit or manage R‑loops to promote tumor progression, particularly through the epigenetic silencing of differentiation genes and modulation of replication stress responses. Furthermore, emerging therapeutic strategies targeting R‑loop biology were examined, including small molecules that induce synthetic lethality, gene‑based interventions and combination approaches that exploit R‑loop vulnerabilities. Challenges in targeting R‑loops and future directions, including multi‑omics profiling and biomarker development, were also addressed. Understanding the complex interplay between R‑loops and HCC offers promising avenues for novel diagnostic and therapeutic approaches for this malignancy.

Hepatocellular carcinoma (HCC), the predominant form of primary liver cancer, represents a substantial global health challenge with limited treatment options. The voltage‑dependent anion channel (VDAC), a critical mitochondrial outer membrane protein, has emerged as a pivotal regulator in HCC pathogenesis. Dysregulation of VDAC expression and function disrupts mitochondrial metabolism, confers resistance to apoptosis and promotes tumor proliferation. Mechanistically, VDAC facilitates HCC progression through metabolic reprogramming, evasion of programmed cell death and crosstalk with multiple oncogenic signaling pathways. Current VDAC‑targeted therapeutic approaches, including small‑molecule inhibitors and metabolic modulators, have demonstrated promising preclinical efficacy in inducing apoptosis and suppressing tumor growth. Notably, these agents may overcome therapeutic resistance and exhibit synergistic effects with conventional therapies. However, several challenges persist, particularly in elucidating isoform‑specific functions, optimizing pharmacokinetic profiles and identifying predictive biomarkers for patient stratification. The present comprehensive review critically evaluates the mechanistic involvement of VDAC in HCC progression, assesses emerging targeting strategies and proposes future research directions to establish VDAC as a viable precision medicine target for HCC management.