Roundabout homolog 1 inhibits proliferation via the YY1-ROBO1-CCNA2-CDK2 axis in human pancreatic cancer

Chen, Q.; Zhang, J.; Lu, Zheng; Jiang, Kuirong; Miao, Yi

doi:10.1016/j.hpb.2020.11.598

Cited by 2 publications

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“…CCNA2 could also act as a significant downstream facilitating tumor progression. Chen et al suggested that ROBO1 could promote the development of pancreatic cancer via CCNA2/CDK axis [36]. Interestingly, our study illustrated that CCNA2 could enhance the development of ccRCC via several immunerelated signals, including immunodeficiency, natural killer cell-mediated cytotoxicity pathway, and IL6-JAK-STAT3 pathways.…”

Section: Discussionsupporting

confidence: 48%

CCNA2 as an Immunological Biomarker Encompassing Tumor Microenvironment and Therapeutic Response in Multiple Cancer Types

Jiang

Zhou

Gong

et al. 2022

Oxidative Medicine and Cellular Longevity

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Background. Cancer is a major threat to human health worldwide. Although recent innovations and advances in early detection and effective therapies such as targeted drugs and immune checkpoint inhibitors have saved more lives of cancer patients and improved their quality of life, our knowledge about cancer remains largely unknown. CCNA2 belongs to the cell cyclin family and has been demonstrated to be a tumorigenic gene in multiple solid tumor types. The aim of the present study was to make a comprehensive analysis on the role of CCNA2 at a pancancer level. Methods. Multidatabases were collected to evaluate the different expression, prognostic value, DNA methylation, tumor mutation burden, microsatellite instability, mismatch repair, tumor immune microenvironment, and drug sensitivity of CCNA2 across pancancer. IHC was utilized to validate the expression and prognostic value of CCNA2 in ccRCC patients from SMMU cohort. Results. CCNA2 was differentially expressed in most cancer types vs. normal tissues. CCNA2 may significantly influence the prognosis of multiple cancer types, especially clear cell renal cell carcinoma (ccRCC). CCNA2 was also frequently mutated in most cancer types. Notably, CCNA2 was significantly correlated with immune cell infiltration and immune checkpoint inhibitory genes. In addition, CCNA2 was also strongly related to drug resistance. Conclusion. CCNA2 may prove to be a new biomarker for prognostic prediction, tumor immunity assessment, and drug susceptibility evaluation in pancancer level, especially in ccRCC.

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Section: Discussionsupporting

confidence: 48%

CCNA2 as an Immunological Biomarker Encompassing Tumor Microenvironment and Therapeutic Response in Multiple Cancer Types

Jiang

Zhou

Gong

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…While an unregulated level of ROBO1 expression in PC tumor stroma was found to support tumor invasiveness and metastasis [36], ROBO1 overexpression in PC cells (PANC-1 and MiaPaca-2) was found to reduce cell proliferation, suggesting a tumor suppressive effect [37]. Our data for HUVECs containing exosomal miR-29b showed ROBO1 overexpression could rescue a decrease in VEGF expression, as well as decreases in cell migration and tube formation after miR-29b mimic transfection.…”

Section: Discussionmentioning

confidence: 63%

Tumor-Derived Exosomal miR-29b Reduces Angiogenesis in Pancreatic Cancer by Silencing ROBO1 and SRGAP2

Wang

Yang

Zhuang

et al. 2022

Journal of Immunology Research

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Background. Exosomal miR-29b reportedly plays a role during cancer metastasis. However, its exact function and underlying mechanism during pancreatic cancer (PC) have not been investigated. Methods. Exosomes from PC cells were prepared and identified. Transmission electron microscopy (TEM) and confocal microscopy were used to examine structural characteristics of the exosomes and verify their internalization by human umbilical vein endothelial cells (HUVECs). The tube formation and migration abilities of HUVECs were detected. VEGF content was assessed by ELISA. GW4869 was used to suppress exosome release. Luciferase reporter assays were performed to verify the predicted interaction of miR-29b with ROBO1 and SRGAP2 mRNA. Results. Exosomal miRNA-29b was differentially expressed in the conditioned medium of PC cells. Exosomes from PC cells were verified by TEM and western blotting. Treatment with the exosomal inhibitor (GW4869) prevented an increase in miR-29b expression and recused the reduced VEGF expression and tube formation and migration abilities of HUVECs cocultured with BxPC3 and AsPC-1 cells that overexpressed miR-29b. Furthermore, the downregulation of ROBO1 and SRGAP2 in cocultured HUVECs was also reduced after additional treatment with GW4869. After incubation with miR-29b exosomes, HUVECs had lower VEGF concentrations and reduced migration and tube formation rates; however, those effects were eliminated by subsequent transfection with the miR-29b inhibitor. Luciferase reporter assays verified the interaction of miR-29b with ROBO1 and SRGAP2. That interaction was also supported by rescue assays showing that overexpression of ROBO1 and SRGAP2 also reduced the antiangiogenic effect of exosomal miR-29b in HUVECs. Conclusion. Exosomal miR-29b originating from PC cells protected HUVECs from PC cell-induced angiogenesis by attenuating ROBO1 and SRGAP2 expression. Our findings suggest a strategy for treating PC.

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Roundabout homolog 1 inhibits proliferation via the YY1-ROBO1-CCNA2-CDK2 axis in human pancreatic cancer

Cited by 2 publications

References 0 publications

CCNA2 as an Immunological Biomarker Encompassing Tumor Microenvironment and Therapeutic Response in Multiple Cancer Types

CCNA2 as an Immunological Biomarker Encompassing Tumor Microenvironment and Therapeutic Response in Multiple Cancer Types

Tumor-Derived Exosomal miR-29b Reduces Angiogenesis in Pancreatic Cancer by Silencing ROBO1 and SRGAP2

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