JMJD5 inhibits lung cancer progression by regulating glucose metabolism through the p53/TIGAR pathway

Area of Science:

• Oncology
• Molecular Biology
• Cancer Metabolism

Background:

• Metabolic reprogramming fuels tumor progression and proliferation.
• The tumor suppressor p53 influences glucose metabolism and the Warburg effect.
• Jumonji C domain-containing protein 5 (JMJD5) is a known negative regulator of p53, but its role in metabolic reprogramming is unclear.

Purpose of the Study:

• To investigate the role of JMJD5 in p53-mediated metabolic reprogramming in non-small cell lung cancer (NSCLC).
• To elucidate the molecular mechanisms by which JMJD5 affects tumor glucose metabolism and proliferation.

Main Methods:

• Knockdown of JMJD5 in p53 wild-type NSCLC cells.
• Analysis of TIGAR expression, glycolysis, and pentose phosphate pathway activity.
• In vitro cell proliferation assays and in vivo xenograft tumor growth studies.
• Correlation analysis of JMJD5 and TIGAR expression with patient prognosis.

Main Results:

• JMJD5 knockdown increased TIGAR expression in NSCLC cells, suppressing glycolysis and promoting the pentose phosphate pathway.
• JMJD5 knockdown enhanced NSCLC cell proliferation and tumor growth, an effect reversed by TIGAR silencing.
• Low JMJD5 expression correlated with high TIGAR levels and poor prognosis in lung cancer patients.

Conclusions:

• JMJD5 acts as a key regulator of tumor glucose metabolism via the p53/TIGAR pathway.
• JMJD5 inhibition promotes NSCLC progression by altering metabolic pathways.
• JMJD5 and TIGAR represent potential therapeutic targets for lung cancer treatment.