Cell Biology International最新文献

Hypoxia is a common phenomenon for solid tumors due to a lack of effective vascular system, and has been deemed as an important factor that drives the progression of thyroid cancer (TC) via altering the characteristics of tumor cells. The present study suggested that hypoxic TC cells enhanced cancer stem cell properties and progression of TC by delivering long intergenic non-protein coding RNA 665 (LINC00665)-containing exosomes. Specifically, TPC1 cells were exposed to normoxic or hypoxic environment, and it was found that hypoxic TPC1 cells-secreted exosomes (H-exo) were enriched with LINC00665, compared to normoxic TPC1 cells-derived exosomes (N-exo). In addition, by establishing the in vitro exosomes-TC cells coculture system, we found that in contrast to N-exo, H-exo apparently promoted cell proliferation, epithelial mesenchymal transition (EMT) and cancer stem cell properties via delivering LINC00665. This was supported by the in vivo results that H-exo transferred LINC00665 to promote tumorigenesis and the expression of EMT and stemness-associated markers in xenograft tumor-bearing mice models. Further mechanical experiments validated that LINC00665 combined with EPHB4 mRNA to sustain its stability to enhance cancer aggressiveness of TC. Altogether, our findings verified that hypoxic TC cells-secreted exosomes regulated the LINC00665/EPHB4 axis to enhance cancer stem cell properties of TC, providing novel signatures for TC diagnosis and therapy.

The transcription factor brain and muscle Arnt-like protein-1 (BMAL1) is a clock protein involved in various diseases, including atherosclerosis and cancer. However, BMAL1's involvement in kidney fibrosis and the underlying mechanisms remain largely unknown, a gap addressed in this study. Analysis through Masson's trichrome and Sirius red staining revealed that all groups exposed to unilateral ureteral obstruction showed increased BMAL1 protein expression accompanied by increased TGF-β1 expression and elevated key fibrosis markers, including α-SMA, compared with sham groups. Although TGF-β1 induced BMAL1 protein expression accompanied by increased α-SMA expression in NRK-49F cells, the REV-ERBα agonist GSK4112, a transcriptional repressor of BMAL1, or siRNA targeting BMAL1 significantly inhibited TGF-β1-induced α-SMA expression. Furthermore, BMAL1 knockdown significantly suppressed TGF-β1-induced NOX4/ROS/p38 pathways in NRK-49F cells. Thus, BMAL1 positively regulates TGF-β1-induced signaling associated with fibrotic responses via the NOX4/ROS/p38 pathway. Overall, this study uncovers BMAL1 as a promising therapeutic target for preventing and treating kidney fibrosis, potentially preventing renal failure.

cryptococcus neoformans (C. neoformans) is a crucial opportunistic fungus that possesses an encapsulated fungal pathogen. The cryptococcal capsule is mainly composed of the polysaccharide glucuronoxylomannan (GXM). Macrophages form the first-line innate defense against cryptococcosis; however, the underlying mechanism remains unclear. In this study, GXM-treated RAW264.7 macrophages showed a notably reduced survival rate and increased apoptosis, accompanied by the promoted inducible nitric oxide synthase (iNOS) expression and NO production. Signal transducer and activator of transcription 1 (STAT1) expression was also found to be directly proportional to GXM concentration; STAT1 knockdown could alleviate GXM-induced proliferation decrease and apoptosis increase of macrophages, as well as reduce M1 polarization, iNOS expression and NO release. In conclusion, this study concluded that GXM was the main virulence factor of C. neoformans, which is critical in determining the mechanism of GXM-mediated protective immune response postinfection. The STAT1 signal pathway mediates the effect of GXM stimulation on macrophages, potentially providing a reference for further understanding the biological role of GXM.

RETRACTION: K.-q. Zhang, X.-d. Chu, “GANT61 Plays Antitumor Effects by Inducing Oxidative Stress through the miRNA-1286/RAB31 Axis in Osteosarcoma,” Cell Biology International 45, no. 1 (2020): 61–73, https://doi.org/10.1002/cbin.11467.

The above article, published online on 16 September 2020, in Wiley Online Library (http://onlinelibrary.wiley.com/), has been retracted by agreement between the journal Editor-in-Chief, Xuebiao Yao; and John Wiley & Sons Ltd.  A third party notified the publisher that this article had reused images that had been used in multiple different publications, each by different sets of authors.

Specifically, images from this article have been re-used from the following publications which had published before or near the same time: (Lei, et al. 2020 [https://doi.org/10.2147/OTT.S214514]); (Sun, et al. 2020 [https://doi.org/10.1002/cam4.2723]); (Hu, et al. 2020 [https://doi.org/10.2147/CMAR.S260693]); (Zhao, et al. 2020 [https://doi.org/10.21037/atm-20-5586]); (Ma, et al. 2020 [https://doi.org/10.21037/tcr.2020.04.13]); (Hong, et al. 2020 [https://doi.org/10.18632/aging.103278]); (Chen, et al. 2020 [https://doi.org/10.1002/cam4.2839]); (Wu, et al. 2019 [https://doi.org/10.3233/cbm-190534]); (Chen, et al. 2020 [https://doi.org/10.21037/tcr-20-940]); (Kang, et al. 2020 [https://doi.org/10.21037/tcr-20-1727]); (Wei, et al. 2020 [https://doi.org/10.2147/DDDT.S222694]); and (Xie, et al. 2020 [https://doi.org/10.21037/atm-20-7201]).

In addition, images that appeared in this article have also been detected in the following subsequent publications: (Zhang & Song 2020 [https://doi.org/10.21037/atm-20-7253]); (Qiao, et al. 2021 [https://doi.org/10.1186/s12885-021-08730-7]); (Lv, et al. 2022 [https://doi.org/10.1080/13880209.2022.2032206]); (Yao, et al. 2022 [https://doi.org/10.1080/21655979.2022.2060776]); and (Zhou, et al. 2021 [https://doi.org/10.21037/atm-20-7365]). The authors did not respond to inquiries by the publisher. The retraction has been agreed to because the evidence of image duplications across different articles, each of which reports on different experimental conditions, fundamentally compromises the conclusions of this article. The authors did not respond to our notice regarding the retraction.

Melatonin (MT), an endogenous hormone secreted by pineal gland, has the sedative, anti-inflammatory and antioxidant functions. However, there are few studies on whether MT affects the proliferation and differentiation of antler chondrocytes. The present study investigated the influences of MT on the proliferation and differentiation of antler chondrocytes, explored its regulation on runt-related transcription factor 2 (RUNX2), NOTCH1 and sonic hedgehog (SHH) signaling, and elucidated their interplays. The results showed that MT promoted the proliferation of antler chondrocytes and induced the differentiation of chondrocytes into hypertrophic chondrocytes as evidenced by the significant increase of collagen type X (COL X), alkaline phosphatase (ALP) and matrix metalloproteinase 13 (MMP13) expression and ALP activity, the well-established markers for hypertrophic chondrocytes, but this effectiveness was neutralized by the addition of MT receptor antagonist. Further analysis indicated that MT activated the NOTCH1 and SHH signaling whose blockage abrogated the inducement of MT on the proliferation and differentiation of antler chondrocytes. SHH was identified as a downstream target of recombination signal binding protein for immunoglobulin kappa J region (RBPJ), a transcription factor of NOTCH1 signaling. Meanwhile, MT stimulated the expression of RUNX2 through activating the SHH signaling whose downstream transcription factor glioma-associated oncogene 1 (GLI1) directly controlled the transcription of RUNX2 through binding to its promoter region. Moreover, repression of GLI1 counteracted the proliferative effect of MT on antler chondrocytes and attenuated the advancement of MT on chondrocyte differentiation, while supplementation of recombinant RUNX2 protein recued above effects. Collectively, MT induced the proliferation and differentiation of antler chondrocytes via RUNX2 dependent on the interaction between NOTCH1 and SHH signaling pathways.

Rare genetic disorders are low in prevalence and hence there is little or no attention paid to them in the mainstream medical industry. One of the ultra-rare neuromuscular disorders, GNE myopathy is caused due to biallelic mutations in the bifunctional enzyme, GNE (UDP N-acetylglucosamine-2-epimerase/N-acetylmannosamine kinase). It catalyses the rate-limiting step in sialic acid biosynthesis. There are no effective treatments for GNE myopathy as the pathomechanism is poorly understood. Pathologically, the disease is characterized by the formation of rimmed vacuoles that contain aggregates of β-amyloid, tau, presenilin etc proteins in muscle biopsy samples. Accumulation of aggregated proteins in the cells may occur due to the failure of the regulated autophagy phenomenon. In the present study, we aim to understand the effect of GNE mutations on autophagy. The cytosolic calcium levels in GNE mutant cells were found to be altered in a GNE mutation-specific manner. The chaperone levels, such as HSP70 and PDI, as well as autophagic markers (LC3II/I ratios) were altered in the GNE mutant cells. Treatment with BAPTA-AM, calcium chelator, significantly restored cytosolic calcium levels in some GNE mutant cells as well as autophagic marker levels and autophagic punctae formation. The effect on the calcium signalling cascade involving CaMKKβ/AMPK/mTOR was studied in the GNE mutant cells. Our study provides insights into the role of calcium in autophagic vacuole formation in the cells with GNE mutations that will have significance towards understanding the pathomechanism of GNE Myopathy and drug target identification for the rare disease.

The high plasticity of cells undergoing epithelial-mesenchymal transition (EMT) promotes increased tumor heterogeneity, and its interaction with tumor-associated stromal cells appears to contribute to developing a stemness phenotype. Cells with these characteristics exhibit increased resistance to chemotherapy and radiotherapy, leading to disease relapse and metastasis. Here, we discuss the activation of the Wnt/β-catenin pathway in promoting EMT and stemness within the context of cellular resistance to these therapies. We discuss whether EMT and cancer stem cells (CSCs) function in conjunction, independently, or if a link is connecting their development. We further propose that this pathway is necessary to establish a connection between these two phenotypes. And suggest that it could hinder the rise of CSCs from treatment-induced EMT cells when inhibited. Understanding this cellular phenomenon might allow the development of new targeted therapies to improve clinical responses, particularly in colorectal cancer.

Mounting evidence indicates the involvement of N6-methyladenosine (m6A) alterations in diverse neurological disorders and the activation of microglia. However, the role of m6A methyltransferase Wilms' tumor 1-associated protein (WTAP) in regulating microglial polarization during ischemic stroke (IS) remains unknown. We performed bioinformatics analysis to identify m6A-related differentially expressed genes in IS and validated these genes in a mouse middle cerebral artery occlusion model and a BV2 cell oxygen-glucose deprivation/reperfusion model. We found that microglial m6A modification was increased, and that WTAP was the most significantly differentially expressed m6A regulator during IS. High expression of WTAP is closely correlated with microglia-mediated neuroinflammation in IS. Mechanistically, WTAP promoted m6A modification, which promoted prostaglandin endoperoxide synthase-2 (PTGS2) by enhancing its mRNA stability. WTAP promoted M1 microglial polarization by elevating PTGS2 expression via m6A modification of PTGS2 mRNA in the oxygen-glucose deprivation/reperfusion model. In conclusion, WTAP is a crucial posttranscriptional regulator that contributes to post-IS neuroinflammation. WTAP knockdown confers cerebral protection by shifting the microglial phenotype from M1 to M2, primarily by reducing PTGS2 mRNA stability in an m6A-dependent manner.

The presence of DNA in the cytosol triggers a protective response from the innate immune system. Cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS–STING) is an essential cytosolic DNA sensor that triggers a potent innate immune response. As a result of this signaling cascade reaction, type I interferon and other immune mediators activate an immune response. The cGAS–STING pathway has great anticancer immunity-boosting potential since it produces type I interferons. The detection of double-stranded DNA (dsDNA) in response to various stimuli initiates a protective host's cGAS–STING signals. So, it is clear that a substantial relationship is expected between cancer biotherapy and the functioning of the cGAS–STING pathway. Several STING agonists with promising outcomes have been created for preclinical cancer therapy research. Notably, immunotherapy has dramatically extended patient survival and radically altered the course of lung cancer treatment, particularly in more advanced instances. However, this method is still ineffective for a large number of lung cancer patients. cGAS–STING can overcome resistance and boost anticancer immunity by stimulating the activity of many pro-inflammatory mediators, augmenting dendritic cell cross-presentation, and initiating a tumor-specific CD8⁺ T cell response. This review aims to present the most recent results on the functionality of the cGAS–STING pathway in cancer progression and its potential as an immunotherapy target, with a focus on lung cancer.