ACOX2 deficiency in primary malignant cardiac tumors

Zhou, Xiangyu; Wang, Hongyan

doi:10.1073/pnas.1701212114

Cited by 9 publications

(8 citation statements)

References 4 publications

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“…Our study highlights the oncogenic property of Acox2 deficiency in tumor progression as those of our previous [ 19 ] and other studies [ 39 ]. Acox2 could be a critical regulator for metabolic homeostasis through post-translational modifications, probably Kcr.…”

Section: Discussionsupporting

confidence: 87%

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Acox2 is a regulator of lysine crotonylation that mediates hepatic metabolic homeostasis in mice

et al. 2022

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Acyl-CoA oxidase 2 (Acox2) is an enzyme involved in peroxisomal bile acid synthesis and branched-chain fatty acid degradation. Acox2 knockout (−/−) mice spontaneously developed liver cancer with marked lymphocytic infiltrate. Tandem-affinity purification coupled with mass spectrometry analysis revealed that Acox2 interacted with methylcrotonoyl-CoA carboxylase followed by co-immunoprecipitation confirmation. Here we reported that non-histone lysine crotonylation (Kcr) levels were downregulated in Acox2−/− mice livers. Interestingly, Kcr signals were concentrated in the nucleus of tumor cells but mostly located in the cytoplasm of adjacent normal liver cells of Acox2−/− mice. Quantitative analysis of the global crotonylome further revealed that 54% (27/50) of downregulated non-histone Kcr sites were located in mitochondrial (11/50) and peroxisomal (17/50) enzymes including Ehhadh, Scp2, Hsd17b4, Crot, Etfa, Cpt1a, Eci1/2, Hadha, Etfdh, and Idh2. Subsequent site-directed mutagenesis and transcriptome analysis revealed that Ehhadh K572cr might have site-specific regulatory roles by downregulating TOP3B expression that lead to increased DNA damage in vitro. Our findings suggested Acox2 is a regulator of Kcr that might play critical role on hepatic metabolic homeostasis.

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Section: Discussionsupporting

confidence: 87%

“…We previously reported that Acox2 deficiency is associated with a metabolic switch in primary malignant cardiac tumor progression [ 19 , 20 ]. ACOX2 homozygous stop-gain (p.Y69*) and missense (p.R225W) mutations have been identified in patients with transaminase elevation and liver fibrosis [ 21 , 22 ].…”

Section: Introductionmentioning

confidence: 99%

Acox2 is a regulator of lysine crotonylation that mediates hepatic metabolic homeostasis in mice

et al. 2022

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“…We have previously reported Acox2 deficiency in patients with primary malignant cardiac tumors (6). In our present study, we found that 28.57% (6/21) of the Acox2 -/mice spontaneously developed HCC, whereas none of the WT mice developed such J o u r n a l P r e -p r o o f tumors ( Supplementary Fig.…”

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confidence: 59%

Two sides of NNMT in alcoholic and non-alcoholic fatty liver development

Zhang

Zeng

et al. 2021

Journal of Hepatology

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“…Also, it has been reported that ACOX2 was related to carcinogenesis in human colorectal cancer 22 . Zhou and Wang 23 found that ACOX2 was deficient in primary malignant cardiac tumors. Bjorklund et al 24 reported that ACOX2 could promote the proliferation of estrogen receptor-positive (ER+) breast cancers.…”

Section: Introductionmentioning

confidence: 99%

ACOX2 is a prognostic marker and impedes the progression of hepatocellular carcinoma via PPARα pathway

Zhang

Sun

et al. 2021

Cell Death Dis

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Hepatocellular carcinoma (HCC) has been extensively studied as one of the most aggressive tumors worldwide. However, its mortality rate remains high due to ideal diagnosis and treatment strategies. Uncovering novel genes with prognostic significance would shed light on improving the HCC patient’s outcome. In our study, we applied data-independent acquisition (DIA) quantitative proteomics to investigate the expression landscape of 24 paired HCC patients. A total of 1029 differentially expressed proteins (DEPs) were screened. Then, we compared DEPs in our cohort with the differentially expressed genes (DEGs) in The Cancer Genome Atlas, and investigated their prognostic significance, and found 183 prognosis-related genes (PRGs). By conducting protein–protein interaction topological analysis, we identified four subnetworks with prognostic significance. Acyl-CoA oxidase 2 (ACOX2) is a novel gene in subnetwork1, encodes a peroxisomal enzyme, and its function in HCC was investigated in vivo and in vitro. The lower expression of ACOX2 was validated by real-time quantitative PCR, immunohistochemistry, and Western blot. Cell Counting Kit-8 assay, wound healing, and transwell migration assay were applied to evaluate the impact of ACOX2 overexpression on the proliferation and migration abilities in two liver cancer cell lines. ACOX2 overexpression, using a subcutaneous xenograft tumor model, indicated a tumor suppressor role in HCC. To uncover the underlying mechanism, gene set enrichment analysis was conducted, and peroxisome proliferator-activated receptor-α (PPARα) was proposed to be a potential target. In conclusion, we demonstrated a PRG ACOX2, and its overexpression reduced the proliferation and metastasis of liver cancer in vitro and in vivo through PPARα pathway.

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ACOX2 deficiency in primary malignant cardiac tumors

Cited by 9 publications

References 4 publications

Acox2 is a regulator of lysine crotonylation that mediates hepatic metabolic homeostasis in mice

Acox2 is a regulator of lysine crotonylation that mediates hepatic metabolic homeostasis in mice

Two sides of NNMT in alcoholic and non-alcoholic fatty liver development

ACOX2 is a prognostic marker and impedes the progression of hepatocellular carcinoma via PPARα pathway

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