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

Abstract

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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“…The role of ACY1 in CRC remains unclear. Bing and co-workers [ 86 ] observed that the level of ACY1 mRNA and protein is positively associated with the TNM stage, and the inhibition of ACY1 expression leads to the reduction of proliferation and the increase of apoptosis in CRC cells. These results indicate that in CRC, ACY1 has a tumor-promoting function.…”