TERC Stimulates Fatty Acid Metabolism to Promote Bladder Cancer Progression

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Muscle-invasive bladder cancer (MIBC) is aggressive and prone to metastasis, necessitating better understanding of its molecular drivers.
• Identifying key molecular mechanisms of bladder cancer aggressiveness is crucial for developing anti-metastasis strategies.

Purpose of the Study:

• To investigate the role of the long non-coding RNA telomerase RNA component (TERC) in bladder cancer progression.
• To elucidate the molecular pathways through which TERC promotes bladder cancer aggressiveness.
• To evaluate TERC as a potential diagnostic biomarker for urothelial carcinoma.

Main Methods:

• Quantitative analysis of TERC expression in bladder cancer tissues.
• In vitro and in vivo experiments assessing the effects of TERC knockdown on cancer cell proliferation, migration, and invasion.
• Investigation of the m6A modification's role in TERC regulation.
• Analysis of TERC's interaction with PTBP3 and its effect on RXRA mRNA stability.
• Measurement of exosomal TERC levels in patient urine and plasma.

Main Results:

• TERC was significantly upregulated in invasive bladder urothelial carcinoma.
• TERC knockdown inhibited bladder cancer cell proliferation, migration, invasion, and tumor growth.
• TERC promotes bladder cancer by facilitating PTBP3-mediated enhancement of RXRA mRNA stability, remodeling fatty acid metabolism.
• Elevated exosomal TERC in urine and plasma correlated with advanced tumor characteristics and metastasis.

Conclusions:

• TERC plays a critical role in promoting bladder cancer growth, invasion, and metastasis.
• TERC represents a potential therapeutic target for bladder cancer.
• Exosomal TERC in body fluids shows promise as a liquid biopsy biomarker for urothelial carcinoma diagnosis and prognosis.