Functional and Pathological Roles of AHCY

Vizán, Pedro; Croce, Luciano Di; Aranda, Sergi

doi:10.3389/fcell.2021.654344

Cited by 47 publications

(41 citation statements)

References 113 publications

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“…SAM is the second most widely used cofactor after ATP (Vizán et al, 2021). As the main methyl donor, SAM helps the normal liver maintain hypermethylation of the genome (Guo et al, 2020).…”

Section: Linc00662 and Genomic Hypomethylationmentioning

confidence: 99%

LINC00662: A new oncogenic lncRNA with great potential

Zhong

Zhang

et al. 2021

Journal Cellular Physiology

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LINC00662 is located on chromosome 19q11 and is 2085 bp long. It is a long noncoding RNA (lncRNA) newly discovered. LINC00662 expression is upregulated in at least 14 tumors. In addition, the upregulation of LINC00662 expression is also closely related to the poor prognosis of cancer patients and resistance to radiotherapy and chemotherapy.LINC00662 can act as a ceRNA of at least 8 miRNAs. By regulating these miRNAs and their downstream genes, LINC00662 participates in the regulation of four signaling pathways, including the extracellular signal-regulated kinase (ERK) signaling pathway, the Wnt/β-catenin signaling pathway, the Hippo signaling pathway, and the SMD signaling pathway. In addition, the abnormal upregulation of LINC00662 can promote the stem-like features of lung cancer cells. LINC00662 can reduce the promoter methylation level of sadenosylmethionine (SAM)-dependent hepatocellular carcinoma (HCC)-promoting genes by regulating the MAT1A/SAM and AHCY/SAH axes, thereby promoting the activation of oncogenes. This article summarizes the molecular regulation mechanism of LINC00662 in cancer and the diagnostic and prognostic value of LINC00662 in cancer.

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“…SAM is the second most widely used cofactor after ATP (Vizán et al, 2021). As the main methyl donor, SAM helps the normal liver maintain hypermethylation of the genome (Guo et al, 2020).…”

Section: Linc00662 and Genomic Hypomethylationmentioning

confidence: 99%

LINC00662: A new oncogenic lncRNA with great potential

Zhong

Zhang

et al. 2021

Journal Cellular Physiology

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“…S-Adenosylhomocysteine hydrolase (AHCY) is one of the most conserved proteins in living organisms [ 22 ]. AHCY is the only mammalian enzyme known to mediate the reversible catalysis of S-adenosyl-L-homocysteine (SAH) to adenosine (Ado) and homocysteine (Hyc) [ 23 ]. Studies indicated that AHCY was essential for embryonic development and cellular stress, and proper activity of AHCY was required for keeping the cellular methylation potential [ 24 ].…”

Section: Introductionmentioning

confidence: 99%

Wumei Pill Ameliorates AOM/DSS-Induced Colitis-Associated Colon Cancer through Inhibition of Inflammation and Oxidative Stress by Regulating S-Adenosylhomocysteine Hydrolase- (AHCY-) Mediated Hedgehog Signaling in Mice

Wang

Ding

Wang

et al. 2022

Oxidative Medicine and Cellular Longevity

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Wumei Pill (WMP) is a traditional Chinese herbal formulation and widely used to treat digestive system diseases in clinical. S-Adenosylhomocysteine hydrolase (AHCY) can catalyze the hydrolysis of S-adenosylhomocysteine to adenosine and homocysteine in living organisms, and its abnormal expression is linked to the pathogenesis of many diseases including colorectal cancer (CRC). A previous study reported that WMP could prevent CRC in mice; however, the underlying mechanisms especially the roles of AHCY in WMP-induced anti-CRC remain largely unknown. Here, we investigated the regulatory roles and potential mechanisms of AHCY in WMP-induced anti-CRC. WMP notably alleviated the azoxymethane/dextran sulfate sodium- (AOM/DSS-) induced colitis-associated colon cancer (CAC) in mice. Besides, WMP inhibited the inflammation and oxidative stress in AOM/DSS-induced CAC mice. AHCY was high expression in clinical samples of colon cancer compared to the adjacent tissues. WMP inhibited the AHCY expression in AOM/DSS-induced CAC mice. An in vitro study found that AHCY overexpression induced cell proliferation, colony formation, invasion, and tumor angiogenesis, whereas its knockdown impaired its oncogenic function. AHCY overexpression enhanced, while its knockdown weakened the inflammation and oxidative stress in colon cancer cells. Interestingly, WMP potently suppressed the hedgehog (Hh) signaling in AOM/DSS-induced CAC mice. A further study showed that AHCY overexpression activated the Hh signaling while AHCY knockdown inactivated the Hh signaling. Moreover, activation of the Hh signaling reversed the effect of AHCY silencing on inflammation and oxidative stress in vitro. In conclusion, WMP alleviated the AOM/DSS-induced CAC through inhibition of inflammation and oxidative stress by regulating AHCY-mediated hedgehog signaling in mice. These findings uncovered a potential molecular mechanism underlying the anti-CAC effect of WMP and suggested WMP as a promising therapeutic candidate for CRC.

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“…These effects of EZH2 inhibitor on resulting MG may result from: (i) inhibition of low levels of EZH2 in MG, (ii) inhibition of the non-canonical functions of EZH2, or (iii) off-target effects. DZN is known to inhibit S-adenosylhomocysteine hydrolase (AHCY) [recently reviewed in (Vizán et al, 2021)]. AHCY is widely expressed by retinal neurons and MG; levels of expression are high in resting glia, downregulated in activated glia, and unchanged in retinal neurons following damage (not shown).…”

Section: Discussionmentioning

confidence: 99%

Chromatin access regulates the formation of Müller glia-derived progenitor cells in the retina

Campbell

El‐Hodiri

Torres

et al. 2022

Preprint

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EZH2 (Enhancer of Zeste 2), a key component of the Polycomb Repressor Complex 2 (PRC2), is required for the differentiation of Muller glia (MG) during retinal development. However, nothing is known about the roles of EZH2 and PRC2 in mature or damaged retinas. Herein, we investigate the expression of PRC2-related factors and roles during the formation of Muller glia-derived progenitor cells (MGPCs) in the chick and mouse retinas. In chick, EZH2, PRC2-related factors, and EZH2-activators, JARID2 and AEBP1, are dynamically expressed by MG and MGPCs in damaged retinas. Inhibition of EZH2, EED or JARID2 blocks the formation of MGPCs. Similarly, inhibition of EZH2 suppresses the proliferation of progenitors in the circumferential marginal zone. By using a combination of single cell RNA-seq and single cell ATAC-seq, we find significant changes in gene expression and chromatin access in MG with EZH2 inhibition and NMDA-treatment, and many of these genes are associated with glial and neuronal differentiation. Correlation across gene expression, chromatin access and transcription factor motif access in MG was observed for transcription factors known to covey glial identity and promote retinal development. In the mouse retina, components of the PRC2 complex are downregulated in MG in damaged retinas and inhibition of EZH2 has no effect upon the formation of neuron-like cells from Ascl1-overexpressing MG. We conclude that in the chick, but not mouse, the activity of EZH2 is required for the reprogramming of MG into MGPCs by regulating chromatin access to transcription factors associated with glial differentiation and retinal development.

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Functional and Pathological Roles of AHCY

Cited by 47 publications

References 113 publications

LINC00662: A new oncogenic lncRNA with great potential

LINC00662: A new oncogenic lncRNA with great potential

Wumei Pill Ameliorates AOM/DSS-Induced Colitis-Associated Colon Cancer through Inhibition of Inflammation and Oxidative Stress by Regulating S-Adenosylhomocysteine Hydrolase- (AHCY-) Mediated Hedgehog Signaling in Mice

Chromatin access regulates the formation of Müller glia-derived progenitor cells in the retina

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