BGL3 inhibits papillary thyroid carcinoma progression via regulating PTEN stability

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.