Nur77-activated lncRNA WFDC21P attenuates hepatocarcinogenesis via modulating glycolysis

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• Hepatocellular carcinoma (HCC) is a major global cause of cancer mortality.
• The orphan nuclear receptor Nur77 acts as a tumor suppressor in HCC, but its mechanism is unclear.
• Understanding Nur77's role is crucial for developing new HCC therapies.

Purpose of the Study:

• To elucidate the mechanism by which Nur77 suppresses HCC.
• To identify downstream targets of Nur77 involved in HCC suppression.
• To explore potential therapeutic strategies targeting the Nur77 pathway.

Main Methods:

• Investigated Nur77's transcriptional regulation of long noncoding RNA WFDC21P.
• Assessed the impact of Nur77 and WFDC21P on HCC cell proliferation, growth, and metastasis in vitro and in vivo.
• Analyzed the interaction of WFDC21P with glycolytic enzymes PFKP and PKM2.
• Evaluated the effect of Cytosporone-B (Csn-B) on HCC suppression.

Main Results:

• Nur77 directly activates WFDC21P transcription, inhibiting HCC progression.
• WFDC21P expression correlates with Nur77 in HCC tissues; low WFDC21P indicates poor prognosis.
• WFDC21P suppresses glycolysis by inhibiting PFKP and PKM2 activity.
• Csn-B, a Nur77 agonist, suppresses HCC via WFDC21P.

Conclusions:

• Nur77-WFDC21P axis is a novel tumor suppressor pathway in HCC.
• WFDC21P inhibits HCC by targeting key glycolytic enzymes PFKP and PKM2.
• The Nur77-WFDC21P-glycolysis axis presents a potential therapeutic target for HCC.