ZMYND8 promotes the growth and metastasis of hepatocellular carcinoma by promoting HK2-mediated glycolysis

Dou, Changwei; Mo, Huanye; Chen, Tianxiang; Liu, Jie; Zeng, Yuqun; Li, Shuangshuang; Guo, Cheng; Zhang, Chengwu

doi:10.1016/j.prp.2021.153345

Cited by 10 publications

(4 citation statements)

References 24 publications

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“…ZMYND8 is highly expressed in human breast tumors and promotes breast tumor progression in vitro and in xenograft mouse models (12,13,15). Its tumor growth function has been recently characterized in other human cancers, including acute myeloid leukemia, colorectal cancer, glioblastoma, clear cell renal cell carcinoma, bladder cancer, and liver cancer (11,14,(17)(18)(19)(20).…”

Section: Introductionmentioning

confidence: 99%

ZMYND8 is a master regulator of 27-hydroxycholesterol that promotes tumorigenicity of breast cancer stem cells

et al. 2022

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27-Hydroxycholesterol (27-HC) is the most abundant oxysterol that increases the risk of breast cancer progression. However, little is known about epigenetic regulation of 27-HC metabolism and its role in breast tumor initiation. Using genetic mouse mammary tumor and human breast cancer models, we showed here that the histone reader ZMYND8 was selectively expressed in breast cancer stem cells (BCSCs) and promoted epithelial-mesenchymal transition (EMT), BCSC maintenance and self-renewal, and oncogenic transformation through its epigenetic functions, leading to breast tumor initiation. Mechanistically, ZMYND8 was a master transcriptional regulator of 27-HC metabolism. It increased cholesterol biosynthesis and oxidation but blocked cholesterol efflux and 27-HC catabolism, leading to accumulation of 27-HC in BCSCs. Consequently, 27-HC promoted EMT, oncogenic transformation, and tumor initiation through activation of liver X receptor. These findings reveal that ZMYND8 is an epigenetic booster that drives breast tumor initiation through metabolic reprogramming.

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Section: Introductionmentioning

confidence: 99%

ZMYND8 is a master regulator of 27-hydroxycholesterol that promotes tumorigenicity of breast cancer stem cells

et al. 2022

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“… [ 38 ] 48 NM_001281779 ZMYND8 Promotion of proliferation, migration and invasion in breast cancer and liver cancer. [ 39 , 40 ] 49 XM_005265382 SEMA3F Inhibition of proliferation in oral cancer. [ 41 ] …”

Section: Resultsmentioning

confidence: 99%

An extract from the frass of swallowtail butterfly (Papilio machaon) larvae inhibits HCT116 colon cancer cell proliferation but not other cancer cell types

Nakano,

Sakamoto,

Kitano

et al. 2023

BMC Genomics

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Background The frass of several herbivorous insect species has been utilised as natural medicines in Asia; however, the metabolite makeup and pharmaceutical activities of insect frass have yet to be investigated. Oligophagous Papilionidae insects utilise specific kinds of plants, and it has been suggested that the biochemicals from the plants may be metabolised by cytochrome P450 (CYP) in Papilionidae insects. In this study, we extracted the components of the frass of Papilio machaon larvae reared on Angelica keiskei, Oenanthe javanica or Foeniculum vulgare and examined the biological activity of each component. Then, we explored the expression of CYP genes in the midgut of P. machaon larvae and predicted the characteristics of their metabolic system. Results The components that were extracted using hexane, chloroform or methanol were biochemically different between larval frass and the host plants on which the larvae had fed. Furthermore, a fraction obtained from the chloroform extract from frass of A. keiskei-fed larvae specifically inhibited the cell proliferation of the human colon cancer cell line HCT116, whereas fractions obtained from the chloroform extracts of O. javanica- or F. vulgare-fed larval frass did not affect HCT116 cell viability. The metabolites from the chloroform extract from frass of A. keiskei-fed larvae prevented cell proliferation and induced apoptosis in HCT116 cells. Next, we explored the metabolic enzyme candidates in A. keiskei-fed larvae by RNA-seq analysis. We found that the A. keiskei-fed larval midgut might have different characteristics from the O. javanica- or F. vulgare-fed larval metabolic systems, and we found that the CYP6B2 transcript was highly expressed in the A. keiskei-fed larval midgut. Conclusions These findings indicate that P. machaon metabolites might be useful as pharmaceutical agents against human colon cancer subtypes. Importantly, our findings show that it might be possible to use insect metabolic enzymes for the chemical structural conversion of plant-derived compounds with complex structures.

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“…HK2 was recently identified as a downstream target of ZMYND8 in HCC cells, and high expression of ZMYND8 in HCC was associated with glucose consumption, increased lactate, and ATP production in HCC cells, and was associated with patients with unfavorable clinicopathological features and poor prognosis. Silencing ZMYND8 inhibited the proliferation and migration of HCCLM3 cells in vivo (40). MACC1 and STAT3 also enhance glucose metabolism and lactate production through HK2 (41,42).…”

Section: Metabolic Reprogramming Promotes Lactate Production In Hccmentioning

confidence: 95%

Research progress of abnormal lactate metabolism and lactate modification in immunotherapy of hepatocellular carcinoma

Hao²,

Ren³

et al. 2023

Front. Oncol.

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Tumors meet their energy, biosynthesis, and redox demands through metabolic reprogramming. This metabolic abnormality results in elevated levels of metabolites, particularly lactate, in the tumor microenvironment. Immune cell reprogramming and cellular plasticity mediated by lactate and lactylation increase immunosuppression in the tumor microenvironment and are emerging as key factors in regulating tumor development, metastasis, and the effectiveness of immunotherapies such as immune checkpoint inhibitors. Reprogramming of glucose metabolism and the “Warburg effect” in hepatocellular carcinoma (HCC) lead to the massive production and accumulation of lactate, so lactate modification in tumor tissue is likely to be abnormal as well. This article reviews the immune regulation of abnormal lactate metabolism and lactate modification in hepatocellular carcinoma and the therapeutic strategy of targeting lactate-immunotherapy, which will help to better guide the medication and treatment of patients with hepatocellular carcinoma.

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ZMYND8 promotes the growth and metastasis of hepatocellular carcinoma by promoting HK2-mediated glycolysis

Cited by 10 publications

References 24 publications

ZMYND8 is a master regulator of 27-hydroxycholesterol that promotes tumorigenicity of breast cancer stem cells

ZMYND8 is a master regulator of 27-hydroxycholesterol that promotes tumorigenicity of breast cancer stem cells

An extract from the frass of swallowtail butterfly (Papilio machaon) larvae inhibits HCT116 colon cancer cell proliferation but not other cancer cell types

Research progress of abnormal lactate metabolism and lactate modification in immunotherapy of hepatocellular carcinoma

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