Изменение Экспрессии Генов, Вовлеченных В Биосинтез Ретиноевой Кислоты, При Раке Желудка

Abstract

All-trans-retinoic acid (ATRA) is the main biologically active metabolite of retinol (vitamin A) that is required for the regulation of such processes as embryogenesis, tissue differentiation, proliferation, and others. Multiple alcohol, retinol and retinaldehyde dehydrogenases (ADHs, RDHs and RALDHs) as well as aldo-keto reductases (AKRs) catalyze the biosynthesis of retinoic acid in humans. For many normal and neoplastic tissues, the key ATRA-synthesizing enzymes remain unknown. We identified ATRA-generating genes that are expressed in normal and malignant gastric tissues using the transcriptomic database analysis. Quantitative changes in the expression levels of these genes in gastric cancer were determined by semi-quantitative RT-PCR and real-time PCR. Significant decreases in the mRNA levels of genes encoding enzymes that catalyze the reversible oxidation/reduction of retinol and retinaldehyde (ADH4, ADH1B, ADH1C, RDHL, AKR1B10, AKR1B1, and RDH12), as well as the oxidation of retinaldehyde (RALDH1) were revealed in most of the tumor samples. The sharp reduction in the expression levels of genes encoding the key enzymes that convert retinol and retinaldehyde to retinoic acid could lead to a significant decrease in the content of ATRA--the transcriptional regulator of many genes, which in turn can lead to a dysregulation of cell proliferation/differentiation and initiate cancer development.

Identification of the hub genes in gastric cancer through weighted gene co-expression network analysis

“…RDH12, an NADPH-dependent retinal reductase, catalyzes the reduction of all-trans retinal to all-trans retinol (Belyaeva et al, 2005). It was significantly decreased in gastric tumor samples (Kropotova et al, 2013) and cervical squamous cell carcinoma samples (Peng et al, 2015). RDH12 was also one of the differentially expressed metabolism-related genes, and correlated with the prognosis of gastric cancer patients (Wen et al, 2020).…”

Identification of novel hypermethylated genes and demethylating effect of vincristine in colorectal cancer

“…AKR1B1 , aldo-keto reductase family 1, member B1, catalyzes the reduction of aldehydes including the aldehyde form of glucose. It was reported to be downregulated in endometrial cancer and gastric cancer [37,38]. The product of CHST10 , carbohydrate sulfotransferase 10, is known to inhibit the invasiveness of melanoma cells [39].…”

The Role of AKR1B10 in Physiology and Pathophysiology

“…Immunohistochemical analysis has revealed that AKR1B10 is localized in the rapidly renewing epithelial cells of the colon [ 68 ] and stomach [ 69 ]. In contrast, AKR1B10 is markedly decreased or undetectable in cancerous lesions of the colon [ 68 , 70 , 71 , 72 , 73 , 74 , 75 , 76 ] and stomach [ 69 , 77 , 78 , 79 ] ( Table 3 ), as well as in precancerous lesions of the colon (including ulcerative colitis), Crown’s disease, and adenomatous polyps [ 68 , 73 ]. Zu et al [ 73 ] reported that AKR1B10 is critical for protecting host cells from DNA damage induced by electrophilic carbonyl compounds, which are ingested and/or metabolically formed in the intestine.…”