Induction of GNMT by 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranoside through proteasome-independent MYC downregulation in hepatocellular carcinoma

Kant, Rajni; Yen, Chia-Hung; Hung, Jan Jong; Lu, Chung Kuang; Tung, Chien Yi; Chang, Pei Ching; Chen, Yueh Hao; Tyan, Yu‐Chang; Chen, Yi Ming Arthur

doi:10.1038/s41598-018-37292-1

Cited by 13 publications

(29 citation statements)

References 51 publications

(58 reference statements)

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“…GNMT is an enzyme dependent on S-adenosine l-methionine (SAM) that catalyzes the conversion of glycine to creatine (27)(28)(29). SAM dependent methyltransferases are inhibited by S-adenosyl-L-homocysteine (SAH), and GNMT is believed to play a key role in other methyl transfer reactions as a regulator of the cell SAM/SAH ratio (30,31). GNMT is enriched in liver, kidney and other organs and plays an important role in cell protection (32).…”

Section: Discussionmentioning

confidence: 99%

Carnosine alleviates diabetic nephropathy by targeting GNMT, a key enzyme mediating renal inflammation and fibrosis

et al. 2020

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Diabetic nephropathy (DN) is a common microvascular complication of diabetes and the main cause of end-stage nephropathy (ESRD). Inflammation and fibrosis play key roles in the development and progression of diabetic nephropathy. By using in vivo and in vitro DN models, our laboratory has identified the protective role of carnosine (CAR) on renal tubules. Our results showed that carnosine restored the onset and clinical symptoms as well as renal tubular injury in DN. Furthermore, carnosine decreased kidney inflammation and fibrosis in DN mice. These results were consistent with high glucose (HG)-treated mice tubular epithelial cells (MTECs). Using web-prediction algorithms, cellular thermal shift assay (CETSA) and molecular docking, we identified glycine N-methyltransferase (GNMT) as a carnosine target. Importantly, we found that GNMT, a multiple functional protein that regulates the cellular pool of methyl groups by controlling the ratio of S-adenosylmethionine (SAM) to S-adenosylhomocysteine (SAH), was down-regulated significantly in the serum of Type 1 DM patients and renal tissues of DN mice. Moreover, using cultured TECs, we confirmed that the increased GNMT expression by transient transfection mimicked the protective role of carnosine in reducing inflammation and fibrosis. Conversely, the inhibition of GNMT expression abolished the protective effects of carnosine. In conclusion, carnosine might serve as a promising therapeutic agent for DN and GNMT might be a potential therapeutic target for DN.

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Section: Discussionmentioning

confidence: 99%

Carnosine alleviates diabetic nephropathy by targeting GNMT, a key enzyme mediating renal inflammation and fibrosis

et al. 2020

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“…Compound 11 could induce autophagy of HepG2, MCF-7, and A549 by activating MAPK 8/9/10 and JNK signaling pathways [176]. Compound 11 could also enhance GNMT promoter activity by downregulating MYC expression in hepatocellular carcinoma [177]. Compounds 70 , 62 , 63 , 42 , and 19 were isolated from Terminalia calamansanoi with the IC50 values of 65.2, 74.8, 42.2, 38.0, and >100 μ M, respectively, for HL-60 cells [178].…”

Section: Biological Activitymentioning

confidence: 99%

A Comprehensive Review of the Structure Elucidation of Tannins from Terminalia Linn.

Zhang

Liang

Zhou

et al. 2019

Evidence-Based Complementary and Alternative Medicine

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Objectives Tannins with complex structures are important plant resources, which are abundant in the genus Terminalia. Various Terminalia species have been playing an important role in traditional medicine system. A systematic scoping review of Terminalia Linn. research literature for tannins was conducted to summarize the structures of tannins and analysis fragmentation pathway characteristics, which could provide references for the structural analysis of tannins from Terminalia Linn. Methods After an update of the literature search up to September 2018, the terms of Terminalia in all publications were analyzed. Electronic searches were conducted in scifinder and PubMed, and the information from 197 articles in all with regard to the tannin structure study was extracted. Results The compounds of 82 tannins from the genus Terminalia were reviewed. According to the structural differences, they can be divided into three categories, hydrolysable tannins, condensed tannins, and complex tannins, respectively. The fragmentation pathways of 46 identified tannins were analyzed, and the fragmentation rules of tannins were speculated according to different types. Conclusion This review has attracted attention to the active substances in this species such as the tannins summarized in further study. How to improve the extraction and purification technology of tannins from genus Terminalia is an urgent problem to be solved.

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“…ENPP2 encodes ectonucleotide pyrophosphatase/phosphodiesterase 2(ENPP2), also known as Autotaxin, and catalyzes the generation of the lipid-signaling molecule lysophosphatidic acid (LPA) 24 , which participates in the development of the nervous system and tumor progression 25 , 26 . Finally, GNMT plays a role in hepatocarcinogenesis 27 . Thus, these five genes are associated with the malignant progression and treatment resistance of tumors.…”

Section: Discussionmentioning

confidence: 99%

A novel methylation signature predicts radiotherapy sensitivity in glioma

Feng

Shi

et al. 2020

Sci Rep

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Glioblastoma (GBM) is the most common and malignant cancer of the central nervous system, and radiotherapy is widely applied in GBM treatment; however, the sensitivity to radiotherapy varies in different patients. To solve this clinical dilemma, a radiosensitivity prediction signature was constructed in the present study based on genomic methylation. In total, 1044 primary GBM samples with clinical and methylation microarray data were involved in this study. LASSO-COX, GSVA, Kaplan–Meier survival curve analysis, and COX regression were performed for the construction and verification of predictive models. The R programming language was used as the main tool for statistical analysis and graphical work. Via the integration analysis of methylation and the survival data of primary GBM, a novel prognostic and radiosensitivity prediction signature was constructed. This signature was found to be stable in prognosis prediction in the TCGA and CGGA databases. The possible mechanism was also explored, and it was found that this signature is closely related to DNA repair functions. Most importantly, this signature could predict whether GBM patients could benefit from radiotherapy. In summary, a radiosensitivity prediction signature for GBM patients based on five methylated probes was constructed, and presents great potential for clinical application.

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Induction of GNMT by 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranoside through proteasome-independent MYC downregulation in hepatocellular carcinoma

Cited by 13 publications

References 51 publications

Carnosine alleviates diabetic nephropathy by targeting GNMT, a key enzyme mediating renal inflammation and fibrosis

Carnosine alleviates diabetic nephropathy by targeting GNMT, a key enzyme mediating renal inflammation and fibrosis

A Comprehensive Review of the Structure Elucidation of Tannins from Terminalia Linn.

A novel methylation signature predicts radiotherapy sensitivity in glioma

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