LncRNA MEG8 promotes TNF-α expression by sponging miR-454-3p in bone-invasive pituitary adenomas

Area of Science:

• Endocrinology and Bone Biology
• Molecular Oncology
• Genetics and Epigenetics

Background:

• Pituitary adenomas (PAs) can invade bone, but the underlying mechanisms are poorly understood.
• Bone destruction associated with PAs significantly impacts patient prognosis and quality of life.
• Identifying molecular pathways involved in bone invasion is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the molecular mechanism by which long non-coding RNA MEG8, miR-454-3p, and Tumor Necrosis Factor-alpha (TNF-α) interact in bone-invasive pituitary adenomas (BIPAs).
• To elucidate the role of the MEG8/miR-454-3p/TNF-α axis in promoting bone destruction.
• To explore the potential of this pathway as a diagnostic and therapeutic strategy for BIPA patients.

Main Methods:

• Analysis of MEG8 and TNF-α expression levels in BIPA tissues compared to controls.
• Quantification of miR-454-3p expression in BIPA tissues.
• In vitro and in vivo functional assays to assess the impact of MEG8 and miR-454-3p on bone destruction.
• Mechanistic studies to determine the regulatory relationship between MEG8, miR-454-3p, and TNF-α.

Main Results:

• Long non-coding RNA MEG8 and TNF-α were found to be upregulated in BIPA tissues.
• miR-454-3p was significantly downregulated in BIPA tissues, correlating with poorer progression-free survival (PFS).
• Upregulated MEG8 and downregulated miR-454-3p were demonstrated to promote bone destruction.
• MEG8 was shown to sponge miR-454-3p, leading to increased TNF-α expression and subsequent bone destruction.

Conclusions:

• A novel regulatory mechanism involving MEG8/miR-454-3p/TNF-α in BIPAs has been identified.
• This pathway plays a critical role in mediating bone destruction associated with pituitary adenomas.
• The MEG8/miR-454-3p/TNF-α axis represents a potential therapeutic target and diagnostic biomarker for BIPA patients.