MicroRNA-200c Attenuates the Tumor-Infiltrating Capacity of Macrophages

Raue, Rebecca; Frank, Ann-Christin; Fuhrmann, Dominik C.; Cruz‐Ojeda, Patricia de la; Rösser, Silvia; Bauer, Rebekka; Cardamone, Giulia; Weigert, Andreas; Syed, Shahzad N.; Schmid, Tobias; Brüne, Bernhard

doi:10.3390/biology11030349

Cited by 9 publications

(6 citation statements)

References 79 publications

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“…The medium was changes every 2–3 days until day seven of differentiation. Monocytes were now fully differentiated into macrophages and can be used for further experiments [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

SAFit2 reduces neuroinflammation and ameliorates nerve injury-induced neuropathic pain

Wedel

Mathoor

Rauh

et al. 2022

J Neuroinflammation

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Background Neuropathic pain is experienced worldwide by patients suffering from nerve injuries, infectious or metabolic diseases or chemotherapy. However, the treatment options are still limited because of low efficacy and sometimes severe side effects. Recently, the deficiency of FKBP51 was shown to relieve chronic pain, revealing FKBP51 as a potential therapeutic target. However, a specific and potent FKBP51 inhibitor was not available until recently which hampered targeting of FKBP51. Methods In this study, we used the well-established and robust spared nerve injury model to analyze the effect of SAFit2 on nerve injury-induced neuropathic pain and to elucidate its pharmacodynamics profile. Therefore, the mice were treated with 10 mg/kg SAFit2 after surgery, the mice behavior was assessed over 21 days and biochemical analysis were performed after 14 and 21 days. Furthermore, the impact of SAFit2 on sensory neurons and macrophages was investigated in vitro. Results Here, we show that the FKBP51 inhibitor SAFit2 ameliorates nerve injury-induced neuropathic pain in vivo by reducing neuroinflammation. SAFit2 reduces the infiltration of immune cells into neuronal tissue and counteracts the increased NF-κB pathway activation which leads to reduced cytokine and chemokine levels in the DRGs and spinal cord. In addition, SAFit2 desensitizes the pain-relevant TRPV1 channel and subsequently reduces the release of pro-inflammatory neuropeptides from sensory neurons. Conclusions SAFit2 ameliorates neuroinflammation and counteracts enhanced neuronal activity after nerve injury leading to an amelioration of nerve injury-induced neuropathic pain. Based on these findings, SAFit2 constitutes as a novel and promising drug candidate for the treatment of nerve injury-induced neuropathic pain.

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“…The medium was changes every 2–3 days until day seven of differentiation. Monocytes were now fully differentiated into macrophages and can be used for further experiments [ 43 ].…”

Section: Methodsmentioning

confidence: 99%

SAFit2 reduces neuroinflammation and ameliorates nerve injury-induced neuropathic pain

Wedel

Mathoor

Rauh

et al. 2022

J Neuroinflammation

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“…RDX is a cytoskeletal protein, which together with ERZ (ezrin) and MSN (moesin) is called scaffolding proteins ( ERM proteins). RDX promotes cancer cell migration by regulating the degree of macrophage infiltration in the tumor microenvironment by anchoring other proteins to the cell membrane and thus regulating their localization and function ( 60 ). We then examined the efficacy of the prognostic model constructed with these eight genes, dividing patients into high-risk and low-risk groups and observing significant differences in patient outcomes between the groups.…”

Section: Discussionmentioning

confidence: 99%

Exploring PANoptosis in breast cancer based on scRNA-seq and bulk-seq

et al. 2023

Front. Endocrinol.

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BackgroundPANoptosis, a cell death pathway involving pyroptosis, apoptosis, and necroptosis, is pivotal in the development of malignancy. However, in the field of breast cancer, the interaction between PANoptosis and tumor cells has not been thoroughly explored.MethodsWe downloaded breast cancer data and GSE176078 single-cell sequencing dataset from Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases to obtain PANoptosis-associated genes. To construct prognostic models, COX and LASSO regression was used to identify PANoptosis-associated genes with prognostic value. Finally, immune infiltration analysis and differential analysis of biological functions were performed.ResultsRisk grouping was performed according to the prognostic model constructed by COX regression and LASSO regression. The low-risk group showed a better prognosis (P < 0.05) and possessed higher levels of immune infiltration and expression of immune checkpoint-related genes. In addition, the lower the risk score, the higher the degree of microsatellite instability (MSI). Meanwhile, radixin (RDX), the gene with the highest hazard ratio (HR) value among PANoptosis prognosis-related genes, was explicitly expressed in artery Iendothelial cells (ECs) and was widely involved in signaling pathways such as immune response and cell proliferation, possessing rich biological functions.ConclusionWe demonstrated the potential of PANoptosis-based molecular clustering and prognostic features in predicting the survival of breast cancer patients. Furthermore, this study has led to a deeper understanding of the role of PANoptosis in breast cancer and has the potential to provide new directions for immunotherapy of breast cancer.

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“…Of note, the upregulation of miR-200c-3p (6 h, Figure 2 A) by Sorafenib has been shown to be coherently related to the anti-tumoral properties in HepG2 and its plasma levels were associated with increased survival ( Figure 5 A,B). The anti-tumoral role of miR-200c-3p has been related to reduced metastasis in the colorectal xenograft model [ 44 ] and reduces the infiltration capacity of macrophages cocultured with breast cancer cells [ 45 ]. Here, we additionally demonstrated that miR-200c-3p regulated the damage response by altering HSPA1B or NFE2L2 ( Figure 6 ).…”

Section: Discussionmentioning

confidence: 99%

miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma

Cruz‐Ojeda

Schmid

Boix

et al. 2022

Cells

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Background: Sorafenib constitutes a suitable treatment alternative for patients with advanced hepatocellular carcinoma (HCC) in whom atezolizumab + bevacizumab therapy is contraindicated. The aim of the study was the identification of a miRNA signature in liquid biopsy related to sorafenib response. Methods: miRNAs were profiled in hepatoblastoma HepG2 cells and tested in animal models, extracellular vesicles (EVs), and plasma from HCC patients. Results: Sorafenib altered the expression of 11 miRNAs in HepG2 cells. miR-200c-3p and miR-27a-3p exerted an anti-tumoral activity by decreasing cell migration and invasion, whereas miR-122-5p, miR-148b-3p, miR-194-5p, miR-222-5p, and miR-512-3p exerted pro-tumoral properties by increasing cell proliferation, migration, or invasion, or decreasing apoptosis. Sorafenib induced a change in EVs population with an increased number of larger EVs, and promoted an accumulation of miR-27a-3p, miR-122-5p, miR-148b-3p, miR-193b-3p, miR-194-5p, miR-200c-3p, and miR-375 into exosomes. In HCC patients, circulating miR-200c-3p baseline levels were associated with increased survival, whereas high levels of miR-222-5p and miR-512-3p after 1 month of sorafenib treatment were related to poor prognosis. The RNA sequencing revealed that miR-200c-3p was related to the regulation of cell growth and death, whereas miR-222-5p and miR-512-3p were related to metabolic control. Conclusions: The study showed that Sorafenib regulates a specific miRNA signature in which miR-200c-3p, miR-222-5p, and miR-512-3p bear prognostic value and contribute to treatment response.

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MicroRNA-200c Attenuates the Tumor-Infiltrating Capacity of Macrophages

Cited by 9 publications

References 79 publications

SAFit2 reduces neuroinflammation and ameliorates nerve injury-induced neuropathic pain

SAFit2 reduces neuroinflammation and ameliorates nerve injury-induced neuropathic pain

Exploring PANoptosis in breast cancer based on scRNA-seq and bulk-seq

miR-200c-3p, miR-222-5p, and miR-512-3p Constitute a Biomarker Signature of Sorafenib Effectiveness in Advanced Hepatocellular Carcinoma

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