Aminoacylase I deficiency due to <scp>ACY1 mRNA</scp> exon skipping

Ferri, Lorenzo; Funghini, Silvia; Fioravanti, Antonella; Biondi, Emanuele G.; Marca, Giancarlo la; Guerrini, Renzo; Donati, M. A.; Morrone, Amelia

doi:10.1111/cge.12297

Cited by 19 publications

(13 citation statements)

References 17 publications

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“…Although no previous studies, to the best of our knowledge, have suggested that there is an association between ACY1 expression and the severity of colorectal cancer, the results of the current study demonstrated that the level of ACY1 mRNA and protein is positively associated with the TNM stage of the tumor. Previously, ACY1 has been widely recognized for its catalytic activity in the acylation of N-terminal amino acids (6)(7)(8)(20)(21)(22). ACY1 is widely expressed in different organs and previous studies have shown that in the human digestive tract ACY1 is particularly abundant in epithelial cells, but not in stromal cells (23,24).…”

Section: Discussionmentioning

confidence: 99%

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Study of the expression and function of ACY1 in patients with colorectal cancer

Liu

Cao

et al. 2017

Oncology Letters

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Abstract. Aminoacylase 1 (ACY1) is important for regulating the proliferation of numerous types of cancer. However, the expression and mechanisms underlying the function of ACY1 in colorectal cancer remain unclear. In order to investigate the expression and function of ACY1 in colorectal cancer, tumor tissue and blood samples were collected for analysis from 132 patients diagnosed with colorectal cancer. Reverse transcription-quantitative polymerase chain reaction analysis and western blotting identified significantly increased expression of ACY1 mRNA in colorectal tumor tissue (P<0.05 vs. adjacent normal tissue) and notably increased ACY1 protein levels. This ACY1 mRNA expression was found to be positively correlated with tumor stage. In addition, plasma ACY1 concentration was increased in patients with colorectal cancer compared with healthy controls. Furthermore, in vitro knockdown of ACY1 in human colorectal cancer HT-29 cells was shown to inhibit proliferation and increase apoptosis. This effect was found to be associated with the activation of ERK1 and TGF-β1 signaling. In conclusion, the results of the present study suggest that ACY1 promotes tumor progression, and thus may be a potential target for the diagnosis and treatment of colorectal cancer. IntroductionColorectal cancer, the third most common cancer worldwide, is a major public health issue in China and globally (1). Although advances have been made in surgical and medical treatments, ~40% of patients with colorectal cancer succumb to the cancer (2). The early diagnosis and assessment of tumors is an area of intense study; however, it is a complex issue. Previous studies indicate that tumor cells of different clinical stages may exhibit different expression levels of certain biomarkers, which could be used as a target for the diagnosis or treatment of the tumor (3-5). In addition, with ongoing and advancing research into tumor biology, new targets are being identified and studied, including aminoacylase 1 (ACY1) (6).ACY1 is a cytosolic enzyme that deacylates the α-acylated amino acid from the N-terminal peptide of intracellular proteins (6). Following this, terminal acetylated proteins are more stable (7-9). In addition to its function in scavenging N-acylated amino acids, ACY1 has been studied in a number of types of human cancer. In small cell lung cancer (SCLC), renal cell carcinoma and liver cancer ACY1 expression has been demonstrated to be significantly reduced (10-13), suggesting that ACY1 serves a role in inhibiting tumorigenesis. Limited studies have investigated the detailed function and mechanism of ACY1 in tumor proliferation, and certain previous studies have reported that activation of ERK 1/2 and expression of TGF-β may be implicated in this process (13-16). However, the role of ACY1 in gastrointestinal cancer remains unclear. In the present study, the function and regulation of ACY1 in colorectal cancer was investigated through analyzing clinical samples. Materials and methodsPatients and clinical specimens. In total, 160 patients ...

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Section: Discussionmentioning

confidence: 99%

“…The cocktail was subsequently incubated for 5 min at room temperature and added to the cells. The transfection system was kept at 37˚C in 5% CO 2 for 48 h (20)(21)(22). After 48 h, downregulation of ACY1 was measured by qPCR.…”

Section: Methodsmentioning

confidence: 99%

Study of the expression and function of ACY1 in patients with colorectal cancer

Liu

Cao

et al. 2017

Oncology Letters

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“…Values ranging from 0.7 to 1.3 were assumed to be normal based on our previous experience. 20,21 Ten control DNAs and two DNAs from two previously described female relatives of a BTHS patient harbouring a heterozygous deletion of TAZ exons 6-11 (NG_009634.1:g.[9777_9814del; 9911-?_14402del] 4 ) were included in order to validate the assay.…”

Section: Determination Of the X-chromosome Linkage And X-inactivationmentioning

confidence: 99%

Intra-individual plasticity of the TAZ gene leading to different heritable mutations in siblings with Barth syndrome

et al. 2015

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Infantile-onset skeletal myopathy Barth syndrome (OMIM #302060) is caused by mutations in the X-linked TAZ gene and hence usually manifests itself only in hemizygous males. Confirmatory testing is provided by mutational analysis of the TAZ gene and/or by biochemical dosage of the monolysocardiolipin/tetralinoleoyl cardiolipin ratio. Heterozygous females do not usually display a clinical phenotype but may undergo molecular genetic prenatal diagnosis during pregnancy. We characterized two novel and non-identical TAZ gene rearrangements in the offspring of a single female carrier of Barth syndrome. The hg19chrX:g.153634427_153644361delinsKP_123427.1 TAZ gene rearrangement was identified in her affected son, whereas the NM_000116.3(TAZ)c. − 72_109+51del TAZ gene deletion was identified in a male foetus during a subsequent pregnancy. The unaffected mother was surprisingly found to harbour both variants in addition to a wild-type TAZ allele. A combination of breakpoint junction sequencing, linkage analysis and assessment of allelic dosage revealed that the two variants had originated independently from an apparently unstable/mutable TAZ maternal allele albeit via different mutational mechanisms. We conclude that molecular prenatal diagnosis in Barth syndrome families with probands carrying TAZ gene rearrangements should include investigation of the entire coding region of the TAZ gene. The identification of the breakpoint junctions of such gross gene rearrangements is important to ensure accurate ascertainment of carriership with a view to providing appropriate genetic counselling.

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“…Aminoacylase 1 (ACY1, EC 3.5.1.14) deficiency (MIM 609924) is a rare inborn error of metabolism (IEM) characterized by increased urinary excretion of N-acetylated amino acids with the exception of N-acetylaspartic acid (NAA). Since the first report by Van Coster et al (2005) less than 20 additional patients have been described, most of them presenting with heterogeneous neurological symptoms such as psychomotor delay, seizures, intellectual disability (Sass et al 2007;Ferri et al 2013). ACY1 deficiency has also been reported associated with autistic feature in one patient (Tylki-Szymanska et al 2010).…”

Section: Introductionmentioning

confidence: 99%

“…ACY1 is located on the short arm of chromosome 3 (3p21.1) (Naylor et al 1979(Naylor et al , 1982Miller et al 1990;Cook et al 1993), and the protein is highly conserved, supporting an evolutionary role in physiology. Until now ten different mutations have been reported (Van Coster et al 2005;Sass et al 2006Sass et al , 2007Tylki-Szymanska et al 2010;Ferri et al 2013), with no clear-cut phenotype-genotype correlation.…”

Section: Introductionmentioning

confidence: 99%

Isolated Mild Intellectual Disability Expands the Aminoacylase 1 Phenotype Spectrum

et al. 2014

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Aminoacylase 1 (ACY1) deficiency is a rare inborn error of metabolism presenting with heterogeneous neurological symptoms such as psychomotor delay, seizures, intellectual disability and it is characterized by increased urinary excretion of N-acetylated amino acids. We report on a new patient who presented ACY1 deficiency in association with isolated mild intellectual disability, but neither neurological symptoms nor autistic features. The child showed a compound heterozygous mutation (p.Glu233Asp) and a novel p.Ser192Arg fs*64, predicting an unstable transcript and resulting in very low protein levels.This new ACY1 deficient child was identified through regular screening for inborn error of metabolism adopted in our department in all cases of intellectual disability. This report supports a recommendation to perform metabolic investigations in patients with isolated mild intellectual disability.

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Aminoacylase I deficiency due to ACY1 mRNA exon skipping

Cited by 19 publications

References 17 publications

Study of the expression and function of ACY1 in patients with colorectal cancer

Study of the expression and function of ACY1 in patients with colorectal cancer

Intra-individual plasticity of the TAZ gene leading to different heritable mutations in siblings with Barth syndrome

Isolated Mild Intellectual Disability Expands the Aminoacylase 1 Phenotype Spectrum

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