The HACD4 haplotype as a risk factor for atherosclerosis in males

Zivotic, Ivan; Stanković, Aleksandra; Ivančević, Ilija; Končar, Igor; Stanković, Goran; Alavantić, Dragan; Živković, Maja

doi:10.1016/j.gene.2017.10.030

Cited by 2 publications

(3 citation statements)

References 27 publications

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“…We do not consider it a potential marker for breast cancer because of its low mutation rate and role in cancers. The 3-hydroxy acyl-CoA dehydratase 4 (HACD4) is a tumor suppressor similar to CDKN2A and CDKN2B but has not been associated with breast cancer …”

Section: Resultsmentioning

confidence: 99%

“…The 3-hydroxy acyl-CoA dehydratase 4 (HACD4) is a tumor suppressor similar to CDKN2A and CDKN2B but has not been associated with breast cancer. 46 In the case of the DDB1 and CUL4 Associated Factor 6 (DCAF6), there are no targeted therapeutic data available for this gene, and its mutation percentage is also relatively low (4.46%) according to the COSMIC database; however, one of the recent studies claimed the presence of circ_DCAF6 at high levels in breast cancer cells. 47 Regarding its functional roles, a curbed proliferation and stemness by breast cancer cells is observed during circ_DCAF6 absence.…”

Section: ■ Resultsmentioning

confidence: 99%

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Ranking Breast Cancer Drugs and Biomarkers Identification Using Machine Learning and Pharmacogenomics

Mehmood

Nawab

Jin

et al. 2023

ACS Pharmacol. Transl. Sci.

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Breast cancer is one of the major causes of death in women worldwide. It is a diverse illness with substantial intersubject heterogeneity, even among individuals with the same type of tumor, and customized therapy has become increasingly important in this sector. Because of the clinical and physical variability of different kinds of breast cancers, multiple staging and classification systems have been developed. As a result, these tumors exhibit a wide range of gene expression and prognostic indicators. To date, no comprehensive investigation of model training procedures on information from numerous cell line screenings has been conducted together with radiation data. We used human breast cancer cell lines and drug sensitivity information from Cancer Cell Line Encyclopedia (CCLE) and Genomics of Drug Sensitivity in Cancer (GDSC) databases to scan for potential drugs using cell line data. The results are further validated through three machine learning approaches: Elastic Net, LASSO, and Ridge. Next, we selected top-ranked biomarkers based on their role in breast cancer and tested them further for their resistance to radiation using the data from the Cleveland database. We have identified six drugs named Palbociclib, Panobinostat, PD-0325901, PLX4720, Selumetinib, and Tanespimycin that significantly perform on breast cancer cell lines. Also, five biomarkers named TNFSF15, DCAF6, KDM6A, PHETA2, and IFNGR1 are sensitive to all six shortlisted drugs and show sensitivity to the radiations. The proposed biomarkers and drug sensitivity analysis are helpful in translational cancer studies and provide valuable insights for clinical trial design.

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Section: Resultsmentioning

confidence: 99%

Section: ■ Resultsmentioning

confidence: 99%

Ranking Breast Cancer Drugs and Biomarkers Identification Using Machine Learning and Pharmacogenomics

Mehmood

Nawab

Jin

et al. 2023

ACS Pharmacol. Transl. Sci.

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show abstract

“…These downstream genes, whose expression is also reduced with the decrease of MARK4 expression, have important biological functions. HACD4 is a protein-coding gene involved in the biosynthesis and metabolism of fatty acyl-CoA, which is mainly associated with spinocerebellar ataxia and atherosclerosis in men 32 . ACAT2/1 is a membrane protein that is expressed in all tissues and cells throughout the body, and its main function is related to cholesterol metabolism 33 , 34 .…”

Section: Discussionmentioning

confidence: 99%

MARK4 aggravates cardiac dysfunction in mice with STZ-induced diabetic cardiomyopathy by regulating ACSL4-mediated myocardial lipid metabolism

Wu,

Zhang,

Wang

et al. 2024

Sci Rep

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Diabetic cardiomyopathy is a specific type of cardiomyopathy. In DCM, glucose uptake and utilization are impaired due to insulin deficiency or resistance, and the heart relies more heavily on fatty acid oxidation for energy, resulting in myocardial lipid toxicity-related injury. MARK4 is a member of the AMPK-related kinase family, and improves ischaemic heart failure through microtubule detyrosination. However, the role of MARK4 in cardiac regulation of metabolism is unclear. In this study, after successful establishment of a diabetic cardiomyopathy model induced by streptozotocin and a high-fat diet, MARK4 expression was found to be significantly increased in STZ-induced DCM mice. After AAV9-shMARK4 was administered through the tail vein, decreased expression of MARK4 alleviated diabetic myocardial damage, reduced oxidative stress and apoptosis, and facilitated cardiomyocyte mitochondrial fusion, and promoted myocardial lipid oxidation metabolism. In addition, through the RNA-seq analysis of differentially expressed genes, we found that MARK4 deficiency promoted lipid decomposition and oxidative metabolism by downregulating the expression of ACSL4, thus reducing myocardial lipid accumulation in the STZ-induced DCM model.

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The HACD4 haplotype as a risk factor for atherosclerosis in males

Cited by 2 publications

References 27 publications

Ranking Breast Cancer Drugs and Biomarkers Identification Using Machine Learning and Pharmacogenomics

Ranking Breast Cancer Drugs and Biomarkers Identification Using Machine Learning and Pharmacogenomics

MARK4 aggravates cardiac dysfunction in mice with STZ-induced diabetic cardiomyopathy by regulating ACSL4-mediated myocardial lipid metabolism

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