Aldolase A accelerates hepatocarcinogenesis by refactoring c-Jun transcription.
10.1016/j.jpha.2024.101169
- Author:
Xin YANG
1
;
Guang-Yuan MA
1
;
Xiao-Qiang LI
2
;
Na TANG
2
;
Yang SUN
2
;
Xiao-Wei HAO
2
;
Ke-Han WU
1
;
Yu-Bo WANG
1
;
Wen TIAN
2
;
Xin FAN
1
;
Zezhi LI
1
;
Caixia FENG
1
;
Xu CHAO
3
;
Yu-Fan WANG
1
;
Yao LIU
4
;
Di LI
5
;
Wei CAO
1
Author Information
1. Department of Pharmacy, School of Chemistry & Pharmacy, Northwest A&F University, Yangling, Shaanxi, 712100, China.
2. Key Laboratory of Gastrointestinal Pharmacology of Chinese Materia Medica of the State Administration of Traditional Chinese Medicine, School of Pharmacy, Air Force Medical University, Xi'an, 710032, China.
3. The Second Affiliated Hospital of Shaanxi University of Traditional Chinese Medicine, Xianyang, Xi'an, 712046, China.
4. Life Science Research Core Service Platform, Northwest A&F University, Yangling, Shaanxi, 712100, China.
5. National Human Genetic Resources Sharing Service Platform (2005DKA21300), Shanghai, 201023, China.
- Publication Type:Journal Article
- Keywords:
Glycolysis;
Hepatocellular carcinoma;
Nuclear localization;
Transcriptional regulation;
c-Jun
- From:
Journal of Pharmaceutical Analysis
2025;15(7):101169-101169
- CountryChina
- Language:English
-
Abstract:
Hepatocellular carcinoma (HCC) expresses abundant glycolytic enzymes and displays comprehensive glucose metabolism reprogramming. Aldolase A (ALDOA) plays a prominent role in glycolysis; however, little is known about its role in HCC development. In the present study, we aim to explore how ALDOA is involved in HCC proliferation. HCC proliferation was markedly suppressed both in vitro and in vivo following ALDOA knockout, which is consistent with ALDOA overexpression encouraging HCC proliferation. Mechanistically, ALDOA knockout partially limits the glycolytic flux in HCC cells. Meanwhile, ALDOA translocated to nuclei and directly interacted with c-Jun to facilitate its Thr93 phosphorylation by P21-activated protein kinase; ALDOA knockout markedly diminished c-Jun Thr93 phosphorylation and then dampened c-Jun transcription function. A crucial site Y364 mutation in ALDOA disrupted its interaction with c-Jun, and Y364S ALDOA expression failed to rescue cell proliferation in ALDOA deletion cells. In HCC patients, the expression level of ALDOA was correlated with the phosphorylation level of c-Jun (Thr93) and poor prognosis. Remarkably, hepatic ALDOA was significantly upregulated in the promotion and progression stages of diethylnitrosamine-induced HCC models, and the knockdown of A ldoa strikingly decreased HCC development in vivo. Our study demonstrated that ALDOA is a vital driver for HCC development by activating c-Jun-mediated oncogene transcription, opening additional avenues for anti-cancer therapies.
