The MicroRNA-371 Family as Plasma Biomarkers for Monitoring Undifferentiated and Potentially Malignant Human Pluripotent Stem Cells in Teratoma Assays

Salvatori, Daniela; Dorssers, Lambert C. J.; Gillis, Ad J. M.; Perretta, Gemma; Agthoven, Ton van; Fernandes, Maria Gomes; Stoop, Hans; Oosterhuis, J. Wolter; Mummery, Christine L.; Looijenga, Leendert H. J.

doi:10.1016/j.stemcr.2018.11.002

Cited by 22 publications

(28 citation statements)

References 49 publications

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“…In order to extend the reach of our microRNA-identification model, we used a mouse xenograft model already described by us (which contains both benign and malignant teratoma samples as determined by teratoma assay); for details about the origin of animals and related information please refer to [50]. Briefly, the aforementioned (T)GCT cell lines and also human pluripotent stem cells (hPSCs) and induced pluripotent stem cells (IPS) were injected subcutaneously into immunodeficient mice and tumor xenografts grew until a maximum size of 2cm 3 (endpoint), after which they were collected for histological evaluation and microRNA isolation.…”

Section: Mouse Modelmentioning

confidence: 99%

Identification and Validation Model for Informative Liquid Biopsy-Based microRNA Biomarkers: Insights from Germ Cell Tumor In Vitro, In Vivo and Patient-Derived Data

Lobo

Gillis

Berg

et al. 2019

Cells

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Liquid biopsy-based biomarkers, such as microRNAs, represent valuable tools for patient management, but often do not make it to integration in the clinic. We aim to explore issues impeding this transition, in the setting of germ cell tumors, for which novel biomarkers are needed. We describe a model for identifying and validating clinically relevant microRNAs for germ cell tumor patients, using both in vitro, in vivo (mouse model) and patient-derived data. Initial wide screening of candidate microRNAs is performed, followed by targeted profiling of potentially relevant biomarkers. We demonstrate the relevance of appropriate (negative) controls, experimental conditions (proliferation), and issues related to sample origin (serum, plasma, cerebral spinal fluid) and pre-analytical variables (hemolysis, contaminants, temperature), all of which could interfere with liquid biopsy-based studies and their conclusions. Finally, we show the value of our identification model in a specific scenario, contradicting the presumed role of miR-375 as marker of teratoma histology in liquid biopsy setting. Our findings indicate other putative microRNAs (miR-885-5p, miR-448 and miR-197-3p) fulfilling this clinical need. The identification model is informative to identify the best candidate microRNAs to pursue in a clinical setting.

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Section: Mouse Modelmentioning

confidence: 99%

Identification and Validation Model for Informative Liquid Biopsy-Based microRNA Biomarkers: Insights from Germ Cell Tumor In Vitro, In Vivo and Patient-Derived Data

Lobo

Gillis

Berg

et al. 2019

Cells

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“…The reason for the non-expression of the miR by teratoma is probably related to the analogies of GCT biology and the human embryonal development [34,35]. While most of the GCT subtypes mimic early developmental stages of embryonal development and accordingly retain their biochemical characteristics including the microRNA profile of stem cells, the teratoma subtype represents a more advanced and more mature histological subtype that has lost all of the biochemical characteristics of stem cells particularly the typical expression of miR-371a-3p [36].…”

Section: Intracellular Localization Of Mir-371a-3p By Ishmentioning

confidence: 99%

Graded expression of microRNA-371a-3p in tumor tissues, contralateral testes, and in serum of patients with testicular germ cell tumor

et al. 2020

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Copyright: Belge et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Background: Serum levels of microRNA-371a-3p represent a specific tumor marker of testicular germ cell tumors (GCTs) but the origin of circulating miR-371a-3p is not finally resolved. The correlation between miR-levels in tissue and serum is unclear.Results: MiR-levels in GCT tissue are 399-fold higher than in contralateral testicular tissue and 5843-fold higher than in non-testicular tissue. MiR tissue levels correlate with corresponding serum levels (r 2 = 0.181). ISH detected miR-371a-3p intracellularly in GCT cells except teratoma. A low expression was also detected in normal testicular germ cells.Conclusions: Circulating miR-371a-3p is specifically derived from GCT tissue. The miR is present in GCT cells except teratoma. A low expression is also found in normal testicular tissue but not in non-testicular tissue. MiR-371a-3p levels in tissue and serum correlate significantly. This study underscores the usefulness of serum miR-371a-3p as tumor marker of GCT.Patients and methods: Expression levels of miR-371a-3p were concurrently measured in tissues of GCT, contralateral testes (n = 38), and in serum (n = 36) with real time PCR. For control, 5 healthy testicles and 4 non-testicular tissue samples were examined. MiR-levels were compared using descriptive statistical methods. We also performed in situ hybridization (ISH) of GCT tissue with a probe specific for miR-371a-3p.

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“…Previous studies have shown that miRNAs can control the pathological process of II/R injury (Y. Hu et al, ; Z. Li et al, ; Y. Li, Wen, et al, ; Y. Li, Xu, et al, ). In addition, some miRNAs including miR‐375 and miR‐371 have been confirmed as the markers for clinical diagnosis and treatment of diseases (Piano et al, ; Salvatori et al, ). Circulating miRNA‐375 can be considered as a biomarker for active Kaposi's sarcoma in AIDS patients (Piano et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Circulating miRNA‐375 can be considered as a biomarker for active Kaposi's sarcoma in AIDS patients (Piano et al, ). The MiR‐371 family can be used as the plasma biomarkers for monitoring undifferentiated and potentially malignant human pluripotent stem cells (Salvatori et al, ). Besides, some groups have reported that miR‐29b‐3p plays important roles in cell apoptosis, inflammation, and oxidative stress (Jing et al, ; H. Wang et al, ; Xing et al, ; Zhang et al, ).…”

Section: Discussionmentioning

confidence: 99%

“…Li, Xu, et al, 2017). In addition, some miRNAs including miR-375 and miR-371 have been confirmed as the markers for clinical diagnosis and treatment of diseases (Piano et al, 2019;Salvatori et al, 2018). Circulating miRNA-375 can be considered as a biomarker for active Kaposi's sarcoma in AIDS patients (Piano et al, 2019).…”

Section: Overexpression Of Mir-29b-3p Alleviated H/r-caused Injury mentioning

confidence: 99%

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MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

Dai

Zhang

Han

et al. 2019

British J Pharmacology

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Background and Purpose The microRNA miR‐29b‐3p shows important roles in regulating apoptosis and inflammation. However, its effects on intestinal ischaemia/reperfusion (II/R) injury have not been reported. Here we have investigated the functions of miR‐29b‐3p on II/R injury on order to find drug targets to treat the injury. Experimental Approach Two models ‐ in vitro hypoxia/reoxygenation (H/R) of IEC‐6 cells; in vivo, II/R injury in C57BL/6 mice were used. Western blotting and dual‐luciferase reporter assays were used and mimic and siRNA transfection tests were applied to assess the effects of miR‐29b‐3p on II/R injury via targeting TNF receptor‐associated factor 3 (TRAF3). Key Results The H/R procedure decreased cell viability and promoted inflammation and apoptosis in IEC‐6 cells, and the II/R procedure also promoted intestinal inflammation and apoptosis in mice. Expression levels of miR‐29b‐3p were decreased in H/R‐induced cells and II/R‐induced intestinal tissues of mice compared with control group or sham group, which directly targeted TRAF3. Decreased miR‐29b‐3p level markedly increased TRAF3 expression via activating TGF‐α‐activated kinase 1 phosphorylation, increasing NF‐κB (p65) levels to promote inflammation, up‐regulating Bcl2‐associated X expression, and down‐regulating Bcl‐2 expression to trigger apoptosis. In addition, the miR‐29b‐3p mimetic and TRAF3 siRNA in IEC‐6 cells markedly suppressed apoptosis and inflammation to alleviate II/R injury via inhibiting TRAF3 signallimg. Conclusions and Implications The miR‐29b‐3p played a critical role in II/R injury, via targeting TRAF3, which should be considered as a significant drug target to treat the disease.

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The MicroRNA-371 Family as Plasma Biomarkers for Monitoring Undifferentiated and Potentially Malignant Human Pluripotent Stem Cells in Teratoma Assays

Cited by 22 publications

References 49 publications

Identification and Validation Model for Informative Liquid Biopsy-Based microRNA Biomarkers: Insights from Germ Cell Tumor In Vitro, In Vivo and Patient-Derived Data

Identification and Validation Model for Informative Liquid Biopsy-Based microRNA Biomarkers: Insights from Germ Cell Tumor In Vitro, In Vivo and Patient-Derived Data

Graded expression of microRNA-371a-3p in tumor tissues, contralateral testes, and in serum of patients with testicular germ cell tumor

MicroRNA‐29b‐3p reduces intestinal ischaemia/reperfusion injury via targeting of TNF receptor‐associated factor 3

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