Abstract

The solute carrier (SLC) superfamily genes encode more than 300 members that are responsible for the transmembrane transportation of many essential endogenous and exogenous compounds ranging from nutrients to drugs. SLCs are highly expressed in metabolic organs such as the liver, regulating the homeostasis of metabolites and the disposition of drugs. In contrast to their well-studied roles in physiological and pharmacological processes, little is known about the relationship between SLCs and cancer progression. Here, we aimed to explore the potential role of SLCs in progression and prognosis of hepatocellular carcinoma (HCC), one of the most commonly diagnosed cancers and leading causes of death worldwide. By performing bioinformatics analyses of HCC dataset from The Cancer Genome Atlas database, we identified three novel signature SLCs (SLC51B, SLC22A15, and SLC2A1) that are indicative of poor prognosis. Further functional analyses suggested the potential regulation of the three prognostic SLCs on cell proliferation and metastasis. Subsequent knockdown experiments performed in HCC cell lines showed that all three prognostic SLCs positively regulated the proliferation of HCC cells, among which SLC22A15 and SLC2A1 were required for migration and invasion of the cells, demonstrating remarkable consistency with the roles identified by bioinformatics methods in HCC. Therefore, our study provides a novel prognostic biomarker for HCC and reveals the significant roles of SLCs in HCC progression, which might have been undervalued in the past.

中文翻译：

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预后 SLC 家族基因促进肝细胞癌的细胞增殖、迁移和侵袭

摘要

溶质载体 (SLC) 超家族基因编码 300 多个成员，这些成员负责从营养素到药物的许多重要内源性和外源性化合物的跨膜运输。SLCs在肝脏等代谢器官中高度表达，调节代谢物的稳态和药物的分布。与它们在生理和药理过程中的作用相比，SLC 与癌症进展之间的关系知之甚少。在这里，我们旨在探索 SLC 在肝细胞癌 (HCC) 的进展和预后中的潜在作用，肝细胞癌是全球最常见的癌症之一，也是导致死亡的主要原因。通过对来自癌症基因组图谱数据库的 HCC 数据集进行生物信息学分析，我们确定了三个新的签名 SLC。SLC51B、SLC22A15和SLC2A1 ) 表明预后不良。进一步的功能分析表明三种预后 SLC 对细胞增殖和转移的潜在调节作用。随后在 HCC 细胞系中进行的敲除实验表明，所有三种预后 SLC 均正向调节 HCC 细胞的增殖，其中SLC22A15和SLC2A1是细胞迁移和侵袭所必需的，表明与生物信息学方法在 HCC 中确定的作用显着一致。因此，我们的研究为 HCC 提供了一种新的预后生物标志物，并揭示了 SLC 在 HCC 进展中的重要作用，这在过去可能被低估了。