Seung Yeon Ha, Hyo Sook Song, Jin-Young Kim, Youn-Hee Choi, Ji Ha Choi
{"title":"SLC5A8错义变异对其肿瘤抑制功能的影响","authors":"Seung Yeon Ha, Hyo Sook Song, Jin-Young Kim, Youn-Hee Choi, Ji Ha Choi","doi":"10.3346/jkms.2025.40.e146","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Solute carrier family-5 member-8 (SLC5A8) serves as a plasma membrane transporter for monocarboxylates, such as lactate, butyrate, pyruvate, acetate, propionate, nicotinate, and β-hydroxybutyrate. SLC5A8 can suppress colorectal cancer (CRC), and its tumor-suppressive function is mainly associated with butyrate, propionate, and pyruvate, which inhibit histone deacetylase. Although SLC5A8 is an important tumor suppressor, the impact of <i>SLC5A8</i> variants on its tumor-suppressive function have not been reported. In this study, we investigated the effects of <i>SLC5A8</i> missense variants on the expression and tumor-suppressive function of the transporter using various in vitro assays.</p><p><strong>Methods: </strong>Common <i>SLC5A8</i> missense variations were identified using data from the Database of Single-Nucleotide Polymorphisms of the National Center for Biotechnology Information. We generated HCT116 and DLD-1 cell lines stably overexpressing wild-type <i>SLC5A8</i> or <i>SLC5A8</i> variants. The effect of each variant on SLC5A8 expression was examined via immunoblotting. Finally, using colony-formation, wound-healing, and invasion assays, we investigated whether the decrease in SLC5A8 expression resulting from its variants could affect the tumor-suppressive function of the transporter.</p><p><strong>Results: </strong>We identified two common missense single-nucleotide polymorphisms of <i>SLC5A8</i>, Val193Ile (rs1709189) and Met490Ile (rs164365), and assembled two major haplotypes of <i>SLC5A8</i>. Among these haplotypes, haplotype 1 contained wild-type <i>SLC5A8</i> mRNA sequences and H2 contained two variants: Val193Ile and Met490Ile. Val193Ile and H2 significantly decreased SLC5A8 expression. These variants significantly increased the proliferation, migration, and invasion abilities of CRC cells.</p><p><strong>Conclusion: </strong>Decreased SLC5A8 expression caused by missense <i>SLC5A8</i> variants appeared to significant impair the tumor-suppressive function of the transporter.</p>","PeriodicalId":16249,"journal":{"name":"Journal of Korean Medical Science","volume":"40 27","pages":"e146"},"PeriodicalIF":2.3000,"publicationDate":"2025-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260602/pdf/","citationCount":"0","resultStr":"{\"title\":\"Effect of <i>SLC5A8</i> Missense Variants on Its Tumor-Suppressive Function.\",\"authors\":\"Seung Yeon Ha, Hyo Sook Song, Jin-Young Kim, Youn-Hee Choi, Ji Ha Choi\",\"doi\":\"10.3346/jkms.2025.40.e146\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>Solute carrier family-5 member-8 (SLC5A8) serves as a plasma membrane transporter for monocarboxylates, such as lactate, butyrate, pyruvate, acetate, propionate, nicotinate, and β-hydroxybutyrate. SLC5A8 can suppress colorectal cancer (CRC), and its tumor-suppressive function is mainly associated with butyrate, propionate, and pyruvate, which inhibit histone deacetylase. Although SLC5A8 is an important tumor suppressor, the impact of <i>SLC5A8</i> variants on its tumor-suppressive function have not been reported. In this study, we investigated the effects of <i>SLC5A8</i> missense variants on the expression and tumor-suppressive function of the transporter using various in vitro assays.</p><p><strong>Methods: </strong>Common <i>SLC5A8</i> missense variations were identified using data from the Database of Single-Nucleotide Polymorphisms of the National Center for Biotechnology Information. We generated HCT116 and DLD-1 cell lines stably overexpressing wild-type <i>SLC5A8</i> or <i>SLC5A8</i> variants. The effect of each variant on SLC5A8 expression was examined via immunoblotting. Finally, using colony-formation, wound-healing, and invasion assays, we investigated whether the decrease in SLC5A8 expression resulting from its variants could affect the tumor-suppressive function of the transporter.</p><p><strong>Results: </strong>We identified two common missense single-nucleotide polymorphisms of <i>SLC5A8</i>, Val193Ile (rs1709189) and Met490Ile (rs164365), and assembled two major haplotypes of <i>SLC5A8</i>. Among these haplotypes, haplotype 1 contained wild-type <i>SLC5A8</i> mRNA sequences and H2 contained two variants: Val193Ile and Met490Ile. Val193Ile and H2 significantly decreased SLC5A8 expression. These variants significantly increased the proliferation, migration, and invasion abilities of CRC cells.</p><p><strong>Conclusion: </strong>Decreased SLC5A8 expression caused by missense <i>SLC5A8</i> variants appeared to significant impair the tumor-suppressive function of the transporter.</p>\",\"PeriodicalId\":16249,\"journal\":{\"name\":\"Journal of Korean Medical Science\",\"volume\":\"40 27\",\"pages\":\"e146\"},\"PeriodicalIF\":2.3000,\"publicationDate\":\"2025-07-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12260602/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Korean Medical Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.3346/jkms.2025.40.e146\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, GENERAL & INTERNAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Korean Medical Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.3346/jkms.2025.40.e146","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, GENERAL & INTERNAL","Score":null,"Total":0}
Effect of SLC5A8 Missense Variants on Its Tumor-Suppressive Function.
Background: Solute carrier family-5 member-8 (SLC5A8) serves as a plasma membrane transporter for monocarboxylates, such as lactate, butyrate, pyruvate, acetate, propionate, nicotinate, and β-hydroxybutyrate. SLC5A8 can suppress colorectal cancer (CRC), and its tumor-suppressive function is mainly associated with butyrate, propionate, and pyruvate, which inhibit histone deacetylase. Although SLC5A8 is an important tumor suppressor, the impact of SLC5A8 variants on its tumor-suppressive function have not been reported. In this study, we investigated the effects of SLC5A8 missense variants on the expression and tumor-suppressive function of the transporter using various in vitro assays.
Methods: Common SLC5A8 missense variations were identified using data from the Database of Single-Nucleotide Polymorphisms of the National Center for Biotechnology Information. We generated HCT116 and DLD-1 cell lines stably overexpressing wild-type SLC5A8 or SLC5A8 variants. The effect of each variant on SLC5A8 expression was examined via immunoblotting. Finally, using colony-formation, wound-healing, and invasion assays, we investigated whether the decrease in SLC5A8 expression resulting from its variants could affect the tumor-suppressive function of the transporter.
Results: We identified two common missense single-nucleotide polymorphisms of SLC5A8, Val193Ile (rs1709189) and Met490Ile (rs164365), and assembled two major haplotypes of SLC5A8. Among these haplotypes, haplotype 1 contained wild-type SLC5A8 mRNA sequences and H2 contained two variants: Val193Ile and Met490Ile. Val193Ile and H2 significantly decreased SLC5A8 expression. These variants significantly increased the proliferation, migration, and invasion abilities of CRC cells.
Conclusion: Decreased SLC5A8 expression caused by missense SLC5A8 variants appeared to significant impair the tumor-suppressive function of the transporter.
期刊介绍:
The Journal of Korean Medical Science (JKMS) is an international, peer-reviewed Open Access journal of medicine published weekly in English. The Journal’s publisher is the Korean Academy of Medical Sciences (KAMS), Korean Medical Association (KMA). JKMS aims to publish evidence-based, scientific research articles from various disciplines of the medical sciences. The Journal welcomes articles of general interest to medical researchers especially when they contain original information. Articles on the clinical evaluation of drugs and other therapies, epidemiologic studies of the general population, studies on pathogenic organisms and toxic materials, and the toxicities and adverse effects of therapeutics are welcome.