2. Academic Validation
  3. RNA-binding domain 2 of nucleolin is important for the autophagy induction of curcumol in nasopharyngeal carcinoma cells

RNA-binding domain 2 of nucleolin is important for the autophagy induction of curcumol in nasopharyngeal carcinoma cells

  • Phytomedicine. 2023 Apr 26;115:154833. doi: 10.1016/j.phymed.2023.154833.
Guoxiang Liu 1,  Juan Wang 2,  Mengjie Han 1,  Xiaojuan Li 1,  Luwei Zhou 1,  Tong Dou 1,  Yisa Liu 1,  Mengjie HuangFu 1,  Xiao Guan 1,  Yan Wang 1,  Wei Tang 1,  Zhangchi Liu 1,  Linjun Li 1,  Hongfang Ding 1,  Xu Chen 3
Affiliations

Affiliations

  • 1 Department of Pharmacy, Guilin Medical University, 541199 Guilin, PR China.
  • 2 Department of Pharmacy, Guilin Medical University, 541199 Guilin, PR China; Education Department of Guangxi Zhuang Autonomous Region, Key Laboratory of Pharmacognosy, 541199, PR China; Guangxi Key Laboratory of Molecular Medicine in Liver Injury and Repair, Guilin Medical University, 541001, PR China; Guangxi Health Commission Key Laboratory of Basic Research in Sphingolipid Metabolism Related Diseases, the Affiliated Hospital of Guilin Medical University, 541001 Guilin, Guangxi, PR China; Faculty of Basic Medicine, Guilin Medical University, No. 109, 541004 Guilin, PR China.
  • 3 Department of Pharmacy, Guilin Medical University, 541199 Guilin, PR China. Electronic address: [email protected].
PMID: 37137203 DOI: 10.1016/j.phymed.2023.154833
Abstract

Background & aims: Excessive Autophagy induces cell death and is regarded as the treatment of Cancer therapy. We have confirmed that the anti-cancer mechanism of curcumol is related to Autophagy induction. As the main target protein of curcumol, RNA binding protein nucleolin (NCL) interacted with many tumor promoters accelerating tumor progression. However, the role of NCL in cancer Autophagy and in curcumol's anti-tumor effects haven't elucidated. The purpose of the study is to identify the role of NCL in nasopharyngeal carcinoma Autophagy and reveal the immanent mechanisms of NCL played in cell Autophagy.

Methods & results: In the current study, we have found that NCL was markedly upregulated in nasopharyngeal carcinoma (NPC) cells. NCL overexpression effectively attenuated the level of Autophagy in NPC cells, and NCL silence or curcumol treatment obviously aggravated the Autophagy of NPC cells. Moreover, the attenuation of NCL by curcumol lead a significant suppression on PI3K/Akt/mTOR signaling pathway in NPC cells. Mechanistically, NCL was found to be directly interact with Akt and accelerate Akt phosphorylation, which caused the activation of the PI3K/Akt/mTOR pathway. Meanwhile, the RNA Binding Domain (RBD) 2 of NCL interacts with Akt, which was also influenced by curcumol. Notably, the RBDs of NCL delivered Akt expression was related with cell Autophagy in the NPC.

Conclusion: The results demonstrated that NCL regulated cell Autophagy was related with interaction of NCL and Akt in NPC cells. The expression of NCL play an important role in Autophagy induction and further found that was associated with its effect on NCL RNA-binding domain 2. This study may provide a new perspective on the target protein studies for natural medicines and confirm the effect of curcumol not only regulating the expression of its target protein, but also influencing the function domain of its target protein.

Keywords

Autophagy; Curcumol; Nasopharyngeal carcinoma; Nucleolin; PI3K/AKT/mTOR; RNA-binding domain.

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