BGL3 inhibits papillary thyroid carcinoma progression via regulating PTEN stability

M Zhao1, F Yang2, C Sang1

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

Abstract

Insights

The long non-coding RNA BGL3 inhibits papillary thyroid carcinoma (PTC) progression by stabilizing PTEN. Reduced BGL3 levels correlate with advanced PTC, suggesting its potential as a therapeutic target and prognostic biomarker.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Papillary thyroid carcinoma (PTC) is a common endocrine malignancy.
  • Long non-coding RNAs (lncRNAs) are increasingly recognized for their roles in cancer.
  • The specific function of BGL3 in PTC remains uninvestigated.

Purpose of the Study:

  • To elucidate the clinical significance and biological function of BGL3 in human PTC.
  • To explore BGL3 as a potential diagnostic or therapeutic target for PTC.

Main Methods:

  • Quantitative real-time polymerase chain reaction (qRT-PCR) to assess BGL3 expression in 85 PTC and normal tissue pairs.
  • In vitro assays (CCK-8, colony formation, EdU, wound healing) to evaluate BGL3's effects on PTC cell behavior.
  • Mechanistic studies including ChIP, Co-IP, RNA pull-down, and luciferase reporter assays.
  • In vivo xenograft models in nude mice to assess BGL3's impact on tumor growth and metastasis.

Main Results:

  • BGL3 expression was significantly downregulated in PTC tissues compared to normal tissues, repressed by the oncogene Myc.
  • Lower BGL3 levels were associated with larger tumor size, lymph node metastasis, advanced TNM stage, and poorer prognosis.
  • Overexpression of BGL3 suppressed PTC cell proliferation and migration in vitro and reduced tumor size and lung metastasis in vivo.
  • BGL3 interacts with PTEN in the cytoplasm, enhancing OTUD3-mediated de-ubiquitination of PTEN, thereby increasing PTEN stability and inhibiting the PI3K/AKT signaling pathway.

Conclusions:

  • BGL3 plays a critical tumor-suppressive role in PTC through post-translational regulation of PTEN protein stability.
  • BGL3 demonstrates potential as a novel therapeutic target and prognostic biomarker for human PTC.

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