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Targeting neuronal pas domain protein 2 and KN motif/ankyrin repeat domains 1:Advances in type 2 diabetes therapy

World Journal of Diabetes 2024年第11期15卷 2173-2176页

作者： Chun-Han Cheng Wen-Rui Hao Tzu-Hurng Cheng Department of Medical Education Linkou Chang Gung Memorial HospitalTaoyuan 33305Taiwan Division of Cardiology Department of Internal MedicineShuang Ho HospitalMinistry of Health and WelfareTaipei Medical UniversityNew Taipei 23561Taiwan Division of Cardiology Department of Internal MedicineSchool of MedicineCollege of MedicineTaipei Medical UniversityTaipei 11002Taiwan Department of Biochemistry School of MedicineCollege of MedicineChina Medical UniversityTaichung 404328Taiwan

This editorial summarizes the latest literature on the roles of neuronal pas domain protein 2 and KN motif/ankyrin repeat domain 1 in type 2 diabetes(T2D).We highlight their involvement inβ-cell dysfunction,explore their potential as therapeutic targets,and discuss the implications for new treatment *** offer valuable insights into relevant gene regulation and cellular mechanisms relevant for the targeted management of T2D.

关键词： Type 2 diabetes neuronal pas domain protein 2 KN motif and ankyrin repeat domain 1 β-cell dysfunction Therapeutic target

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Circadian Clock Gene Npas2 promotes reprogramming of glucose metabolism in Hepatocellular Carcinoma cells

Circadian Clock Gene NPAS2 promotes reprogramming of glucose...

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2018年中国肿瘤标志物学术大会暨第十二届肿瘤标志物青年科学家论坛

作者： Jibin Li Peng Yuan Jiansheng Zhang Jing Zhao Tao Yang Xiaoyu Long Yiran Hou Feng Zhou Hongxin Zhang Jinliang Xing State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine the Fourth Military Medical University Department of Pain Treatment Tangdu Hospital the Fourth Military Medical University

Emerging evidences show that dysregulation of circadian genes is closely associated with tumor development by participating in the cancer hallmarks of proliferative signaling maintenance, cell death resistance, replicative immortality and metastasis activation. However, whether circadian genes regulates the metabolism reprogramming required for tumor cell proliferation and invasion is ***, we show that Npas2, one of the core circadian molecules, significantly contributed to the reprogramming of glucose metabolism mainly by two mechanisms. On one hand, Npas2 upregulated the expression of glycolytic genes HK2, PKM2 and Glut1, which directly activated the aerobic glycolysis. On the other hand, Npas2 downregulated peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC-1α), a crucial regulator of mitochondrial biogenesis, which in turn directly repressed mitochondrial respiration. Mechanistically, HIF-1 a was found to be a direct transcriptional target of Npas2, which mediated both the upregulation of glycolytic genes of HK2,PKM2 and Glut1, and downregulation of mitochondrial regulator PGC-1α in HCC cells. Moreover, in vitro and in vivo assays indicated that the Npas2-mediated reprogramming of glucose metabolism reprogramming played a critical role in tumor growth and metastasis of ***: Our findings demonstrate that Npas2 plays a critical role in the regulation of tumor cell glucose metabolism reprogramming, which indicates that Npas2 may serve as an important therapeutic target to normalize glucose metabolic aberrations responsible for HCC progression.

关键词： neuronal pas domain protein 2 circadian rhythm Glycolysis Mitochondrial respiration Hepatocellular carcinoma Tumor growth and metastasis

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Circadian Clock Gene Npas2 promotes reprogramming of glucose metabolism in Hepatocellular Carcinoma cells

Circadian Clock Gene NPAS2 promotes reprogramming of glucose...

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2017年中国肿瘤标志物学术大会暨第十一届肿瘤标志物青年科学家论坛

作者： Jibin Li Peng Yuan Hongxin Zhang Jinliang Xing State Key Laboratory of Cancer Biology and Experimental Teaching Center of Basic Medicine the Fourth Military Medical University Department of Pain Treatment Tangdu Hospitalthe Fourth Military Medical University

Aims: Emerging evidences show that dysregulation of circadian genes is closely associated with tumor development by participating in the cancer hallmarks of proliferative signaling maintenance, cell death resistance, replicative immortality and metastasis activation. However, whether circadian genes regulates the metabolism reprogramming required for tumor cell proliferation and invasion is unknown. Methods: In the present study, we systematically investigated the role of Npas2 in the reprogramming of glucose metabolism, as well as its role in the growth and metastasis of HCC cells both in vitro and in vivo. Moreover, the molecular meachnisms governing Npas2-mediated glucose metabolismreprogramming were further explored. Results: Our results showed that Npas2, one of the core circadian molecules, significantly contributed to the reprogramming of glucose metabolism through a Hif-1 a-dependent way in HCC cells mainly by two mechanisms. On one hand, Npas2 upregulated the expression of glycolytic genes HK2, PKM2 and Glut1 by activating transcription of Hif-1 a, which in turn directly activated the aerobic glycolysis. On the other hand, Npas2 downregulated Peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC-1α) by activating transcription of Hif-1 a, which in turn directly repressed mitochondrial biogenesis and respiration. Moreover, in vitro and in vivo assays indicated that the Npas2-mediated reprogramming of glucose metabolism reprogramming played a critical role in tumor growth and metastasis of HCC. Conclusion: Our findings demonstrate that Npas2 plays a critical role in tumor cell metabolism reprogramming regulation, which indicates that Npas2 may serve as an important therapeutic target to normalize metabolic aberrations responsible for HCC progression.

关键词： neuronal pas domain protein 2 circadian rhythm Glycolysis Mitochondrial respiration Hepatocellular carcinoma Tumor growth and metastasis

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