Cell Biology International最新文献

Aluminum (Al) was a nonessential toxic metal in the environment. Al exposure had been widely demonstrated to cause cognitive impairment and neuronal damage. However, the neurotoxicology mechanism of Al was still not summarized through the oxidative stress, inflammation, apoptosis, and gut microbiota. Ginsenosides, natural active components derived from ginseng, had garnered significant attention due to its antioxidant and neuroprotective properties. Although the neurotoxic mechanisms of Al had been elucidated, the treatment of ginsenosides on Al exposure was elusive. This review explores the suppressive feasibility of ginsenosides on the Al-induced neurotoxicity through oxidative stress, inflammatory factors, apoptosis, and intestinal microbiota. Ginsenoside Rb1, Rk3, and Rg1 exhibits anti-inflammatory, anti-oxidative stress, anti-apoptosis, and refinement the gut microbiota composition. But the direct evidence is scarce in the Al-induce neuro disease. Compared with donepezil, ginsenosides exhibit a synergistic advantage encompassing pathological intervention—neuroprotection—metal clearance. Thus, ginsenosides may have potential therapeutic intervention to mitigate Al-induced neurotoxicity. However, the precise mechanisms underlying these effects warrant further investigation.

Micronuclei (MN) are small extranuclear chromosomal fragments that arise from genomic instability and serve as established biomarkers for genotoxicity and disease susceptibility. Once considered only markers of disease, they are now recognized as active, causative drivers of disease progression, driven by emerging evidence of epigenetic regulation within these structures. The micronucleus assay is recognized as a cost-effective and minimally invasive method for monitoring genotoxicity resulting from both chronic and early exposure to environmental factors such as arsenic and lead, as well as from genetic instability associated with cancer progression. This review critically examines the expanding role of MN beyond traditional cytogenetic endpoints, with particular emphasis on recent insights into their epigenetic landscape. Mass spectrometry-based studies have demonstrated that MN possess distinct histone posttranslational modification signatures compared to primary nuclei, including alterations in H3K27ac, H3K9ac, and H3K18ac. These modifications affect chromatin structure, gene expression, and DNA repair mechanisms. In the context of xenobiotic exposures, MN-associated epigenetic changes may function as early indicators of disease progression. Additionally, rupture of the MN envelope can activate innate immune responses through the cGAS–STING pathway or result in chromothripsis, both of which contribute to cancer progression. The concept of “Micronuclear Epigenetics” is highlighted, with its potential application in high-throughput diagnostic platforms, particularly liquid biopsy, discussed. This approach may enhance early detection and risk stratification in exposure-induced toxicity and diseases such as cancer.

Microtubules are subject to dynamic regulation through post-translational modifications, with phosphorylation serving as a key mechanism. The human kinome, comprising over 500 protein kinases, represents a comprehensive regulatory network. Some of these kinases precisely regulate microtubule dynamics and organization, both spatially and temporally, by modulating various microtubule-associated proteins or by directly binding to microtubules. This review, based on a systematic and kinome-wide perspective across multiple physiological systems, provides a comprehensive overview and in-depth analysis of the key kinase families that regulate microtubules, covering both direct and indirect mechanisms. The complex interactions between these kinases and microtubules are not only vital for normal cellular physiology but are often disrupted in various diseases, particularly cancer and neurodegenerative disorders. By synthesizing this knowledge, our work enhances the understanding of kinase–mediated microtubule regulation and lays a foundation for the future development of targeted therapeutic strategies.

Replication factor C (RFC), a multimeric protein with ATPase activity, plays a crucial role in DNA replication and repair. RFC4, one of its subunits, is aberrantly expressed in various malignant tumors, including colorectal cancer (CRC). Nevertheless, the impact of RFC4 on CRC metastasis remains to be elucidated. In this study, we systematically examined the effects of RFC4 silencing on the proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and Wnt/β-catenin signaling pathway in CRC cells in vitro. Additionally, we further explored the regulatory role of RFC4 in liver metastasis of CRC cells in vivo. Finally, BML-284, a known activator of the Wnt/β-catenin signaling pathway, was employed to validate the underlying mechanism by which RFC4 modulates the invasive phenotype of CRC cells. The results demonstrated that RFC4 was significantly overexpressed in CRC cell lines. Upon silencing of RFC4, the proliferation, migration, and invasion capabilities of CRC cells were markedly attenuated, and the EMT process as well as Wnt/β-catenin signaling pathway activity were effectively suppressed. Notably, RFC4 silencing significantly reduced liver metastasis of CRC cells in a nude mouse model. However, the inhibitory effects of RFC4 silencing on CRC cells proliferation, migration, invasion, and EMT were partially reversed by the intervention of the Wnt/β-catenin signaling pathway activator BML-284. Altogether, these results indicate that RFC4 plays a critical role in promoting CRC metastasis, and its mechanism of action may involve the regulation of Wnt/β-catenin signaling pathway activation to facilitate EMT.

The decidua, a dynamic and heterogeneous maternal tissue essential for pregnancy maintenance, has emerged as a key contributor to preeclampsia (PE) pathogenesis. Using methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq), we profiled N6-methyladenosine (m⁶A) methylation patterns and mRNA expression in the decidua of early-onset PE (EPE), late-onset PE (LPE), and normal pregnancy (NP) samples. Integrated analysis revealed that differentially methylated genes (DMGs) and differentially expressed genes (DEGs) were significantly enriched in pathways critical for decidualization, including HIF-1, PI3K-AKT, and Rap1 signaling. These pathways exhibited concurrent m⁶A methylation and expression changes, implicating their involvement in PE development. Notably, insulin-like growth factor (IGF1) was hypomethylated and downregulated in PE decidua compared to NP controls. Given IGF1's central role in stromal cell differentiation and decidualization, its dysregulation likely impairs normal decidual function. Validation using external datasets, quantitative PCR, and siRNA knockdown in human endometrial stromal cells confirmed reduced IGF1 expression and its impact on decidual markers like prolactin. Our findings demonstrate that disrupted m⁶A methylation impairs decidualization via IGF1 regulation, offering novel mechanistic insight into PE. This study highlights the importance of epitranscriptomic regulation at the maternal-fetal interface and identifies m⁶A-modified transcripts as potential therapeutic and diagnostic targets in PE.

RETRACTION: Z. Zhang, M. Yang, Y. Wang, L. Wang, Z. Jin, L. Ding, L. Zhang, L. Zhang, W. Jiang, G. Gao, J. Yang, B. Lu, F. Cao, and T. Hu, “Autophagy Regulates the Apoptosis of Bone Marrow-Derived Mesenchymal Stem Cells Under Hypoxic Condition via AMP-Activated Protein Kinase/Mammalian Target of Rapamycin Pathway,” Cell Biology International 40, no. 6 (2016): 671–685. https://doi.org/10.1002/cbin.10604.

The above article, published online on 23 March 2016 in Wiley Online Library (wileyonlinelibrary.com), and its correction (https://doi.org/10.1002/cbin.12142), have been retracted by agreement between the journal Editorial Board, Xuebiao Yao; and John Wiley & Sons Ltd. An investigation by the publisher found several image duplications from other previously published articles: The beta-actin band in Figure 3 C includes overlapping blot sections that appear in an article by different authors [Li et al. 2013 (https://doi.org/10.1371/journal.pone.0076689)]. The AMPK bands in Figure 4 A was duplicated and manipulated from another article by different authors [Peng et al. 2013 (https://doi.org/10.1371/journal.pone.0079739))]. The DAPI Hypoxia/SD + , 3-MA-, Rapamycin+ image in Figure 6 A was duplicated from another article by different authors [Zhang et al. 2013 (https://doi.org/10.1371/journal.pone.0080342]. The investigation also found evidence of duplication between the second and fourth LC3-I bands in Figure 5D. In addition, a third party reported that an article by some of the same authors re-used and manipulated images that also appear in this article [Yang et al. 2018 (https://doi.org/10.1186/s13287-018-1028-5)]. Lastly, the investigation found that the DAPI Hypoxia/SD + , 3-MA-, Rapamycin- image in Figure 6 A also appears in a later article by different authors [Chen et al. 2018 (https://doi.org/10.1159/000488117)].

The authors responded to an inquiry by the publisher and shared original data. A review of their response and the original data found that the explanations for image duplication from previously published articles and within the article were not adequate to explain the identified concerns.

A correction to this article had been published previously on 11 March 2024 (https://doi.org/10.1002/cbin.12142) which replaced multiple images in Figure 5 A and the “Normal” image in Figure 7 F due to errors in those figures. However, the additional concerns in Figures 3, 4, and 6 cast doubt on the accuracy of the data presented in the article. The retraction has been agreed to because the image duplication and manipulation identified have fundamentally compromised the editors' confidence in the results and conclusions presented in the article. The authors disagree with the retraction.

Acquired drug resistance is a major cause of poor prognosis in multiple myeloma (MM). Bortezomib (BTZ), a first-line therapeutic agent, is highly effective in MM; however, resistance remains a significant clinical challenge. Our previous work implicated Solute Carrier Family 19 Member 1 (SLC19A1) in hypoxia and immune modulation, suggesting its potential role in malignant progression. Here, we found that SLC19A1 expression was elevated in MM patients, particularly in those with acquired resistance. Overexpression of SLC19A1 enhanced the proliferation and invasiveness of human myeloma cell lines but did not confer primary BTZ resistance. Using a continuous-BTZ-exposure model, we demonstrated that SLC19A1 overexpression mediated acquired resistance via chronic activation of the stimulator of interferon genes (STING) pathway. This sustained activation triggered the unfolded protein response, dysregulated the endoplasmic reticulum–mitochondrial axis, and induced mitochondrial DNA (mtDNA) release. Treatment with the SLC19A1 inhibitor sulfasalazine or the STING inhibitor H-151 reduced mtDNA release and restored BTZ sensitivity. These findings highlight SLC19A1 and STING signaling as potential therapeutic targets for overcoming acquired drug resistance in MM.

Evasion of programmed cell death, including apoptosis and necroptosis, is a critical hallmark of cancer that contributes to tumorigenesis and chemoresistance. While microRNAs (miRNAs) are known to modulate cell death pathways, the role of specific miRNA families in coordinated death resistance remains incompletely understood. Through functional screening, we identified the miR-148/152 family as potent suppressors of tumor necrosis factor (TNF)-induced cell death, prompting an investigation into their regulatory mechanism in both apoptosis and necroptosis and their oncogenic role. Ectopic expression of miR-148a or miR-152 inhibits TNF-induced apoptosis and necroptosis in multiple human cancer cell lines, accompanied by reduced activation of caspase-8, caspase-3, RIPK1, and RIPK3. Mechanistically, the miR-148/152 family directly target the 3′UTR of RIPK1, which is a critical regulator in TNF-mediated cell death, thus downregulating its expression. Functionally, miR-152 enhances cancer cell proliferation and colony formation. Clinically, high expression of miR-152 correlates with poor prognosis in gastric cancer patients. Importantly, this miRNA confers resistance to cisplatin-induced, RIPK1-mediated cell death, promoting gastric cancer cell survival and proliferation. Our study defines the miR-148/152 family as critical oncogenic drivers that promote cancer cell survival and chemoresistance by directly suppressing RIPK1 expression. These findings highlight this miRNA family as a promising therapeutic target to overcome cell death evasion in cancer.