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Xin Yang, Guang-Yuan Ma, Xiao-Qiang Li, Na Tang, Yang Sun, Xiao-Wei Hao, KeHan Wu, Yu-Bo Wang, Wen Tian, Xin Fan, Zezhi Li, Caixia Feng, Xu Chao, Yu-Fan Wang, Yao Liu, Di Li, Wei Cao. Aldolase A accelerates hepatocarcinogenesis by refactoring c-Jun transcription[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.101169
Citation: Xin Yang, Guang-Yuan Ma, Xiao-Qiang Li, Na Tang, Yang Sun, Xiao-Wei Hao, KeHan Wu, Yu-Bo Wang, Wen Tian, Xin Fan, Zezhi Li, Caixia Feng, Xu Chao, Yu-Fan Wang, Yao Liu, Di Li, Wei Cao. Aldolase A accelerates hepatocarcinogenesis by refactoring c-Jun transcription[J]. Journal of Pharmaceutical Analysis. doi: 10.1016/j.jpha.2024.101169

Aldolase A accelerates hepatocarcinogenesis by refactoring c-Jun transcription

doi: 10.1016/j.jpha.2024.101169
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This work was supported by the National Natural Science Foundation of China (81473329), the Natural Science Basic Research Program of Shaanxi Province (2023-JCJQ-61), the Science and Technology Project of Shaanxi Province in China (2022YWZXPG-01), and the Scientific Research Project of Shaanxi Administration of Traditional Chinese Medicine (2019-GJ-JC012, 2021-04-ZZ-001, 2021-QYPT-003, and 2022-SLRHYQ-004).

  • Received Date: Jun. 15, 2024
  • Rev Recd Date: Nov. 21, 2024
  • Available Online: Dec. 17, 2024
  • 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 ALDOA 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.
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      沈阳化工大学材料科学与工程学院 沈阳 110142

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