Systemic characterization of the SLC family genes reveals SLC26A6 as a novel oncogene in hepatocellular carcinoma

Solute carrier (SLC) transporters play important roles in various physiological and pathological processes, such as cellular uptake of nutrients, cellular metabolism, tumor initiation and chemotherapy resistance. However, little is known about the comprehensive expression profile of SLC genes in human cancers, especially in human hepatocellular carcinoma (HCC).

This study highlights the potential roles of SLC genes in HCC tumorigenesis, and suggested SLC26A6 as a promising therapeutic target in HCC patients.

Comprehensive analysis was performed using the TCGA dataset to evaluate the expression profile and clinical significance of SLC family genes in HCC. Real-time PCR and immunohistochemistry (IHC) assays were conducted to validate the expression of solute carrier family 26 member 6 (SLC26A6) in clinical HCC tissues. Cell Counting Kit-8 (CCK8), colony formation and subcutaneous xenograft tumorigenesis assays were carried out to explore the functional role of SLC26A6 in HCC. Bioinformatic analyses were used to predict the potential molecular mechanism of SLC26A6 in HCC.

We identified 118 differentially expressed SLC genes (DESLCs) and found that there was a preferential enrichment for activated DESLCs in HCC. Clinical-relevant DESLCs identified a poor prognostic HCC subtype exhibiting unique clinicopathological and genomic profiles. SLC26A6 was overexpressed in HCC tissues both in mRNA and protein levels. Knockdown of SLC26A6 suppressed HCC tumorigenesis both in vitro and in vivo, indicating it as a promising therapeutic target. Finally, multifaceted bioinformatic analyses indicated that SLC26A6 might associate with multiple cancer-related pathways. Conclusions: This study highlights the potential roles of SLC genes in HCC tumorigenesis, and suggested SLC26A6 as a promising therapeutic target in HCC patients.