ROS and miRNA Dysregulation in Ovarian Cancer Development, Angiogenesis and Therapeutic Resistance

Stieg, David C.; Wang, Yifang; Liu, Lingzhi; Jiang, Bing-Hua

doi:10.3390/ijms23126702

Cited by 19 publications

(15 citation statements)

References 194 publications

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“…However, physiological levels of ROS are closely associated with the proliferation and migration of VECs in response to various angiogenesis-stimulating factors. ROS can also stimulate VEC proliferation and induce the formation of filopodia through downstream pathways such as ERK and PI3K/AKT [ 47 – 50 ]. Kim et al.…”

Section: Discussionmentioning

confidence: 99%

CD62E- and ROS-Responsive ETS Improves Cartilage Repair by Inhibiting Endothelial Cell Activation through OPA1-Mediated Mitochondrial Homeostasis

Tu,

Pan,

Wang

et al. 2024

Biomater Res

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Background: In the environment of cartilage injury, the activation of vascular endothelial cell (VEC), marked with excessive CD62E and reactive oxygen species (ROS), can affect the formation of hyaluronic cartilage. Therefore, we developed a CD62E- and ROS-responsive drug delivery system using E-selectin binding peptide, Thioketal, and silk fibroin (ETS) to achieve targeted delivery and controlled release of Clematis triterpenoid saponins (CS) against activated VEC, and thus promote cartilage regeneration. Methods: We prepared and characterized ETS/CS and verified their CD62E- and ROS-responsive properties in vitro. We investigated the effect and underlying mechanism of ETS/CS on inhibiting VEC activation and promoting chondrogenic differentiation of bone marrow stromal cells (BMSCs). We also analyzed the effect of ETS/CS on suppressing the activated VEC-macrophage inflammatory cascade in vitro. Additionally, we constructed a rat knee cartilage defect model and administered ETS/CS combined with BMSC-containing hydrogels. We detected the cartilage differentiation, the level of VEC activation and macrophage in the new tissue, and synovial tissue. Results: ETS/CS was able to interact with VEC and inhibit VEC activation through the carried CS. Coculture experiments verified ETS/CS promoted chondrogenic differentiation of BMSCs by inhibiting the activated VEC-induced inflammatory cascade of macrophages via OPA1-mediated mitochondrial homeostasis. In the rat knee cartilage defect model, ETS/CS reduced VEC activation, migration, angiogenesis in new tissues, inhibited macrophage infiltration and inflammation, promoted chondrogenic differentiation of BMSCs in the defective areas. Conclusions: CD62E- and ROS-responsive ETS/CS promoted cartilage repair by inhibiting VEC activation and macrophage inflammation and promoting BMSC chondrogenesis. Therefore, it is a promising therapeutic strategy to promote articular cartilage repair.

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Section: Discussionmentioning

confidence: 99%

CD62E- and ROS-Responsive ETS Improves Cartilage Repair by Inhibiting Endothelial Cell Activation through OPA1-Mediated Mitochondrial Homeostasis

Tu,

Pan,

Wang

et al. 2024

Biomater Res

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“…MiR-497 targets vascular endothelial growth factor A through PI3K/AKT and MAPK/ERK pathways to inhibit ovarian cancer angiogenesis ( 46 ) Overexpression of microRNA-195-5p reduces cisplatin resistance and angiogenesis in ovarian cancer by inhibiting the psat1-dependent GSK3β/β-catenin signaling pathway ( 47 ). However, the role of aberrant regulation of miRNAs in ovarian cancer angiogenesis and development remains to be further investigated, which provides future therapeutic options and targets ( 72 ). Significant advances have been made in exploring the regulatory role of miRNAs in tumor angiogenesis.…”

Section: Mirnas Regulate Tumor Angiogenesis In Tme Of Ovarian Cancermentioning

confidence: 99%

Research progress on anti-ovarian cancer mechanism of miRNA regulating tumor microenvironment

Cui

Liu

et al. 2022

Front. Immunol.

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Ovarian cancer is the most deadly malignancy among women, but its complex pathogenesis is unknown. Most patients with ovarian cancer have a poor prognosis due to high recurrence rates and chemotherapy resistance as well as the lack of effective early diagnostic methods. The tumor microenvironment mainly includes extracellular matrix, CAFs, tumor angiogenesis and immune-associated cells. The interaction between tumor cells and TME plays a key role in tumorigenesis, progression, metastasis and treatment, affecting tumor progression. Therefore, it is significant to find new tumor biomarkers and therapeutic targets. MicroRNAs are non-coding RNAs that post-transcriptionally regulate the expression of target genes and affect a variety of biological processes. Studies have shown that miRNAs regulate tumor development by affecting TME. In this review, we summarize the mechanisms by which miRNAs affect ovarian cancer by regulating TME and highlight the key role of miRNAs in TME, which provides new targets and theoretical basis for ovarian cancer treatment.

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“…The physiological ROS levels contributed to the proliferation, migration and differentiation of tumor cells, while the lethal ROS levels could lead to DNA damage and cell death (Cheng et al, 2013;Wang et al, 2013). ROS was related to chemo-resistance in some tumor cells (Ledoux et al, 2003;Stieg et al, 2022). Therefore, it is essential for illuminating the effect of ROS on glioma cells and its underlying mechanisms involved in drug resistance.…”

Section: Introductionmentioning

confidence: 99%

Hypoxia promotes temozolomide resistance in glioblastoma cells via ROS- mediated up-regulation of TRPM2

Zhao,

peng,

zhu

et al. 2024

Preprint

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Background: Hypoxia, an essential feature of gliomas, is thought to promote chemo-resistance by regulating reactive oxygen species (ROS) levels. Transient receptor potential melastatin 2 (TRPM2) is one of the ion transport proteins and is involved in the regulation of oxidative stress. However, relationship between ROS and TRPM2 expression in hypoxia-induced temozolomide (TMZ) resistance of glioblastoma cells remains unclear. Methods: U87MG cells were cultured with different concentrations of TMZ for the indicated times under normoxia (21% O2) or hypoxia (2.5% O2). Cell viability was detected with WST-1 test and observed by a neurite outgrowth assay. The intracellular ROS scavenging activity was detected according to the H2DCF-DA method. The cells were also treated with the scavenger of ROS NAC and the inhibitor of TRPM2 2-APB. Impaired mitochondrial membrane potential (ΔΨm) and intensity of intracellular Ca2+ were measured under fluorescence microscope. Online database was used to assess the relationship between MGMT and TRPM2 expression level. Western blot was used to analyze the protein levels of TRPM2, MGMT, MSH3 and APNG. Results: Compared with the normoxia group, hypoxia significantly promoted glioma cells survival after treatment by TMZ (200µM) for 24 h or 48 h, accompanied with reduction of mitochondrial dysfunction and intracellular ROS. However, the baseline levels of ROS were mildly increased under hypoxia, which had no impact on mitochondrial function in glioma cells. Additional, TRPM2 expression was obviously increased under hypoxia and inhibited by NAC in glioma cells. We found that the expression levels of TRPM2 were positively correlated with MGMT both in online database (rho=0.165, P < 0.05) and GBM cancer tissues (r=0.9302, P < 0.05). Over-expression of TRPM2 participated in the up-regulation of APNG and MGMT, but down-regulation of MSH3 in glioma cells under hypoxia. Our findings also demonstrated that the treatment group during NAC or 2-APB add-on could significantly attenuate calcium influx, followed by increasing mitochondrial dysfunction and cytotoxicity in glioma cells, in comparison with TMZ alone. Conclusion: The hypoxia-induced up-regulation of baseline ROS levels contributes to the decrease in the sensitivity of glioma cells to TMZ via promoting demethylation and inhibiting DNA mismatch repair. Moreover, TRPM2-mediated Ca2+ influx attenuates mitochondria dysfunction and then protects glioma cells against TMZ damage. TRPM2 may be a potential target in adjuvant treatment with TMZ for glioblastoma multiforme (GBM) patients.

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ROS and miRNA Dysregulation in Ovarian Cancer Development, Angiogenesis and Therapeutic Resistance

Cited by 19 publications

References 194 publications

CD62E- and ROS-Responsive ETS Improves Cartilage Repair by Inhibiting Endothelial Cell Activation through OPA1-Mediated Mitochondrial Homeostasis

CD62E- and ROS-Responsive ETS Improves Cartilage Repair by Inhibiting Endothelial Cell Activation through OPA1-Mediated Mitochondrial Homeostasis

Research progress on anti-ovarian cancer mechanism of miRNA regulating tumor microenvironment

Hypoxia promotes temozolomide resistance in glioblastoma cells via ROS- mediated up-regulation of TRPM2

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