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FBLN5 is targeted by microRNA?27a?3p and suppresses tumorigenesis and progression in high?grade serous ovarian carcinoma.

ABSTRACT: High-grade serous ovarian carcinoma (HGSOC) is one of the most lethal gynecological malignancies; however, the precise molecular mechanisms have not been fully characterized. Fibulin?5 (FBLN?5) is an extracellular matrix (ECM) glycoprotein, and plays a crucial role in maintaining the stability of ECM structures, regulating cell proliferation and tumorigenesis. In the present study, the expression of FBLN?5, as determined by western blot analysis and immunohistochemistry, was significantly increased in normal fallopian tube (FT) samples compared with that in HGSOC samples, and decreased FBLN5 expression was associated with unfavorable prognosis of HGSOC. Functional characterization revealed that FBLN5 overexpression significantly inhibited migration, invasion and proliferation abilities of ovarian cancer cells in vitro. Furthermore, micro (mi)RNA?27a?3p (miR?27a?3p) was revealed to be increased in HGSOC, and dual?luciferase reporter assay indicated that miR?27a?3p was functioned as a negative regulator of FBLN5 by directly binding with its 3'?untranslated region. Collectively, FBLN5 expression was associated with prognosis, proliferation, and metastasis in HGSOC. We hypothesized that FBLN5 was targeted by miR?27a?3p and may serve as a biomarker and provide a new therapeutic approach for the treatment of HGSOC.

SUBMITTER: Li R

PROVIDER: S-EPMC7550983 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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FBLN5 is targeted by microRNA‑27a‑3p and suppresses tumorigenesis and progression in high‑grade serous ovarian carcinoma.

Li Rongrong R Wu Huan H Jiang Huiyang H Wang Qiuman Q Dou Zhiyuan Z Ma Hanlin H Yan Shi S Yuan Cunzhong C Yang Ning N Kong Beihua B

Oncology reports 20200903 5

High-grade serous ovarian carcinoma (HGSOC) is one of the most lethal gynecological malignancies; however, the precise molecular mechanisms have not been fully characterized. Fibulin‑5 (FBLN‑5) is an extracellular matrix (ECM) glycoprotein, and plays a crucial role in maintaining the stability of ECM structures, regulating cell proliferation and tumorigenesis. In the present study, the expression of FBLN‑5, as determined by western blot analysis and immunohistochemistry, was significantly increa ...[more]

PMID: 32901854

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Project description:BackgroundThe survival rate of patients with advanced high-grade serous ovarian carcinoma (HGSOC) remains disappointing. Clinically translatable orthotopic cell line xenograft models and patient-derived xenografts (PDXs) may aid the implementation of more personalised treatment approaches. Although orthotopic PDX reflecting heterogeneous molecular subtypes are considered the most relevant preclinical models, their use in therapeutic development is limited by lack of appropriate imaging modalities.MethodsWe developed novel orthotopic xenograft and PDX models for HGSOC, and applied a near-infrared fluorescently labelled monoclonal antibody targeting the cell surface antigen CD24 for non-invasive molecular imaging of epithelial ovarian cancer. CD24-Alexa Fluor 680 fluorescence imaging was compared to bioluminescence imaging in three orthotopic cell line xenograft models of ovarian cancer (OV-90luc+, Skov-3luc+ and Caov-3luc+, n = 3 per model). The application of fluorescence imaging to assess treatment efficacy was performed in carboplatin-paclitaxel treated orthotopic OV-90 xenografts (n = 10), before the probe was evaluated to detect disease progression in heterogenous PDX models (n = 7).FindingsApplication of the near-infrared probe, CD24-AF680, enabled both spatio-temporal visualisation of tumour development, and longitudinal therapy monitoring of orthotopic xenografts. Notably, CD24-AF680 facilitated imaging of multiple PDX models representing different histological subtypes of the disease.InterpretationThe combined implementation of CD24-AF680 and orthotopic PDX models creates a state-of-the-art preclinical platform which will impact the identification and validation of new targeted therapies, fluorescence image-guided surgery, and ultimately the outcome for HGSOC patients.FundingThis study was supported by the H2020 program MSCA-ITN [675743], Helse Vest RHF, and Helse Bergen HF [911809, 911852, 912171, 240222, HV1269], as well as by The Norwegian Cancer Society [182735], and The Research Council of Norway through its Centers of excellence funding scheme [223250, 262652].

Dataset Information

FBLN5 is targeted by microRNA?27a?3p and suppresses tumorigenesis and progression in high?grade serous ovarian carcinoma.

Publications

FBLN5 is targeted by microRNA‑27a‑3p and suppresses tumorigenesis and progression in high‑grade serous ovarian carcinoma.

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