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BGL3 inhibits papillary thyroid carcinoma progression via regulating PTEN stability

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Abstract

Purpose

BGL3, a novel long non-coding RNA (lncRNA) that plays a crucial role in several human malignancies. However, the clinical significance and biological function of BGL3 in papillary thyroid carcinoma (PTC) have not been explored. Herein, we aimed to investigate the role of BGL3 in human PTC.

Methods

A total of 85 pairs of PTC and normal tissues were collected for clinicopathological analysis. Expression of BGL3 was determined by quantitative real-time polymerase chain reaction (qRT-PCR). The effects of BGL3 on PTC cells ware determined by CCK-8, colony formation, EdU and wound healing assays. The molecular mechanism underlying BGL3 was tested by ChIP, Co-IP, RNA pull-down and luciferase reporter assays. In vivo experiments were conducted using xenografts in nude mice.

Results

BGL3 was significantly decreased in PTC tissues compared to adjacent normal thyroid tissues, and it was transcriptionally repressed by oncogene Myc. Low BGL3 is positively related to larger tumor size, lymph node metastasis, later TNM stage and poor prognosis. Overexpression of BGL3 inhibited PTC cell proliferation and migration in vitro, and reduced tumor size and lung metastasis nodules in vivo. BGL3 was mainly located in the cytoplasm, in which interacted with PTEN and recruited OTUD3, enhancing the de-ubiquitination effect of OTUD3 on PTEN, resulting in increasing PTEN protein stability and inactivating carcinogenic PI3K/AKT signaling.

Conclusions

Our data underscore the critical tumor-inhibiting role of BGL3 in PTC via post-translational regulation of PTEN protein stability, which may serve as a novel therapeutic target and prognostic biomarker in human PTC.

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Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

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Author information

Authors and Affiliations

  1. Department of General Surgery, Yanqing District Hospital, Beijing and Yanqing Hospital, Peking University Third Hospital, Beijing, People’s Republic of China

    M. Zhao, C. Sang & C. Yan

  2. Department of Orthopedics, Yanqing District Hospital, Beijing and Yanqing Hospital, Peking University Third Hospital, Beijing, People’s Republic of China

    F. Yang

  3. Department of General Surgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China

    Z. Wang

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  1. M. Zhao
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  4. C. Yan
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  5. Z. Wang
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Contributions

(I) Conception and design: MZ, FY; (II) Administrative support: FY, ZJW; (III) Provision of study materials or patients: MZ, CYS, CHY; (IV) Collection and assembly of data: MZ, CYS; (V) Data analysis and interpretation: MZ, FY; (VI) Manuscript writing: All authors; (VII) Final approval of manuscript: All authors.

Corresponding author

Correspondence to Z. Wang.

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The authors declare that they have no conflict of interest.

Ethics approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the Ethics Committee of Beijing Chaoyang Hospital, Capital Medical University, and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. All animals were handled in strict accordance with the “Guide for the Care and Use of Laboratory Animals” and the “Principles for the Utilization and Care of Vertebrate Animals”, which was approved by the Institutional Animal Care and Use Committee of Beijing Chaoyang Hospital, Capital Medical University.

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Written informed consent was obtained from all participants by their parents, and from patients, when appropriate.

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Zhao, M., Yang, F., Sang, C. et al. BGL3 inhibits papillary thyroid carcinoma progression via regulating PTEN stability. J Endocrinol Invest 44, 2165–2174 (2021). https://doi.org/10.1007/s40618-021-01519-2

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  • DOI: https://doi.org/10.1007/s40618-021-01519-2

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