Anti-Inflammatory Action of Heterogeneous Nuclear Ribonucleoprotein A2/B1 in Patients with Autoimmune Endocrine Disorders

Coppola, Antonina; Tomasello, Laura; Guarnotta, Valentina; Pitrone, Maria; Failla, Valentina; Cillino, Salvatore; Feo, Salvatore; Pizzolanti, Giuseppe; Giordano, Carla

doi:10.3390/jcm9010009

Cited by 12 publications

(7 citation statements)

References 45 publications

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“…The electrophoretic separation was performed on 18 cm long strips with a pH range of 3–10. The strips were then equilibrated in a solution containing 50 mM Tris-HCl pH 6.8, 6 M urea, 0.5% SDS, 30% Glycerol, 130 mM DTE and 135 mM Iodoacetamide and then separated on 9–16% linear gradient polyacrylamide gels (SDS-PAGE), with a constant current of 20 mA/gel, as previously described [ 34 , 35 , 36 ]. The gels were silver stained and analyzed with the dedicated Image-Master 2D Platinum software.…”

Section: Methodsmentioning

confidence: 99%

Prognostic and Functional Significant of Heat Shock Proteins (HSPs) in Breast Cancer Unveiled by Multi-Omics Approaches

Buttacavoli

Cara

D’Amico

et al. 2021

Biology

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Heat shock proteins (HSPs) are a well-characterized molecular chaperones protein family, classified into six major families, according to their molecular size. A wide range of tumors have been shown to express atypical levels of one or more HSPs, suggesting that they could be used as biomarkers. However, the collective role and the possible coordination of HSP members, as well as the prognostic significance and the functional implications of their deregulated expression in breast cancer (BC) are poorly investigated. Here, we used a systematic multi-omics approach to assess the HSPs expression, the prognostic value, and the underlying mechanisms of tumorigenesis in BC. By using data mining, we showed that several HSPs were deregulated in BC and significantly correlated with a poor or good prognosis. Functional network analysis of HSPs co-expressed genes and miRNAs highlighted their regulatory effects on several biological pathways involved in cancer progression. In particular, these pathways concerned cell cycle and DNA replication for the HSPs co-expressed genes, and miRNAs up-regulated in poor prognosis and Epithelial to Mesenchymal Transition (ETM), as well as receptors-mediated signaling for the HSPs co-expressed genes up-regulated in good prognosis. Furthermore, the proteomic expression of HSPs in a large sample-set of breast cancer tissues revealed much more complexity in their roles in BC and showed that their expression is quite variable among patients and confined into different cellular compartments. In conclusion, integrative analysis of multi-omics data revealed the distinct impact of several HSPs members in BC progression and indicate that collectively they could be useful as biomarkers and therapeutic targets for BC management.

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Section: Methodsmentioning

confidence: 99%

Prognostic and Functional Significant of Heat Shock Proteins (HSPs) in Breast Cancer Unveiled by Multi-Omics Approaches

Buttacavoli

Cara

D’Amico

et al. 2021

Biology

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“…After homogenization with 50 mM Tris-HCl pH 7.5, 0.003% penicillin, 0.005% streptomycin, tissue lysates were incubated under rotation overnight at 4 • C [44], and then centrifuged several times at 10,000 rpm for 20 min to remove cell debris. Bradford assay was used to quantify protein content, as already reported [34,[45][46][47][48]. Blood, collected into plastic tubes without coagulation accelerators to prevent the release of gelatinases during platelet activation, was centrifuged at 1600× g for 10 min 30 min after collection.…”

Section: Tissue and Sera Samples From Crc Patientsmentioning

confidence: 99%

Integrated Multi-Omics Investigations of Metalloproteinases in Colon Cancer: Focus on MMP2 and MMP9

Buttacavoli

Cara

Roz

et al. 2021

IJMS

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Colorectal cancer (CRC) develops by genetic and epigenetic alterations. However, the molecular mechanisms underlying metastatic dissemination remain unclear and could benefit from multi-omics investigations of specific protein families. Matrix metalloproteinases (MMPs) are proteolytic enzymes involved in ECM remodeling and the processing of bioactive molecules. Increased MMP expression promotes the hallmarks of tumor progression, including angiogenesis, invasion, and metastasis, and is correlated with a shortened survival. Nevertheless, the collective role and the possible coordination of MMP members in CRC are poorly investigated. Here, we performed a multi-omics analysis of MMP expression in CRC using data mining and experimental investigations. Several databases were used to deeply mine different expressions between tumor and normal tissues, the genetic and epigenetic alterations, the prognostic value as well as the interrelationships with tumor immune-infiltrating cells (TIICs). A special focus was placed on to MMP2 and MMP9: their expression was correlated with immune markers and the interaction network of co-expressed genes disclosed their implication in epithelial to mesenchymal transition (EMT) and immune response. Finally, the activity levels of MMP2 and MMP9 in a cohort of colon cancer samples, including tissues and the corresponding sera, was also investigated by zymography. Our findings suggested that MMPs could have a high potency, as they are targeted in colon cancer, and might serve as novel biomarkers, especially for their involvement in the immune response. However, further studies are needed to explore the detailed biological functions and molecular mechanisms of MMPs in CRC, also in consideration of their expression and different regulation in several tissues.

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“…Hence, FAM76B may have functions related to nuclear speckles, such as splicing factor storage and modification (Salichs et al 2009; McGlincy et al 2010). We found in this study that FAM76B interacts with hnRNPA2B1, a heterogeneous nuclear ribonucleoprotein related to mRNA binding and splicing (Peng et al 2021; Moran-Jones et al 2005) that is associated with inflammation (Lin et al 2020; Chen et al 2020; Coppola et al 2019; Hoffmann et al 2011). By in vitro and in vivo experiments, we showed that FAM76B could regulate NF-κB mediated inflammation by influencing the translocation of hnRNPA2B1.…”

Section: Discussionmentioning

confidence: 72%

FAM76B regulates NF-κB-mediated inflammatory pathway by influencing the translocation of hnRNPA2B1

Wang

Zheng

Chai

et al. 2022

Preprint

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FAM76B has been reported to be a nuclear speckle localized protein with unknown function. In this study, FAM76B was first demonstrated to inhibit the NF-κB-mediated inflammatory pathway by affecting the translocation of hnRNPA2B1in vitro. We further showed that FAM76B suppressed inflammation by regulating the NF-κB pathwayin vivousing a traumatic brain injury (TBI) model in FAM76B knockout mice. Lastly, FAM76B was shown to interact with hnRNPA2B1 in human tissues taken from patients with acute, organizing, and chronic TBI, and with different neurodegenerative diseases. The results suggested that FAM76B mediates neuroinflammation by influencing the translocation of hnRNPA2B1in vivoduring TBI repair and neurodegenerative diseases. In summary, we for the first time demonstrated the role of FAM76B in regulating inflammation and further showed that FAM76B could regulate the NF-κB-mediated inflammatory pathway by affecting hnRNPA2B1 translocation, which provides new information for studying the mechanism of inflammation regulation.

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Anti-Inflammatory Action of Heterogeneous Nuclear Ribonucleoprotein A2/B1 in Patients with Autoimmune Endocrine Disorders

Cited by 12 publications

References 45 publications

Prognostic and Functional Significant of Heat Shock Proteins (HSPs) in Breast Cancer Unveiled by Multi-Omics Approaches

Prognostic and Functional Significant of Heat Shock Proteins (HSPs) in Breast Cancer Unveiled by Multi-Omics Approaches

Integrated Multi-Omics Investigations of Metalloproteinases in Colon Cancer: Focus on MMP2 and MMP9

FAM76B regulates NF-κB-mediated inflammatory pathway by influencing the translocation of hnRNPA2B1

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