SLC35A2 expression drives breast cancer progression via ERK pathway activation

Abstract

Alterations in glycosylation are associated with breast tumor formation and progression. Nevertheless, the specific functions and mechanisms of the human major UDP‐galactose transporter‐encoding gene Solute carrier family 35 member A2 (SLC35A2) in breast invasive carcinoma (BRCA) have not been fully determined. Here we reportthat SLC35A2promotesBRCA progression via activating ERK. SLC35A2 expression and prognosis‐predictive significance in pan‐cancer were evaluated using publicdatabases. The upstream non‐coding RNAs (ncRNAs) of SLC35A2 were analyzed, and their expressions and regulations were validated in breast tissues and cell lines by quantitative polymerase chain reaction (qPCR) and dual‐luciferase assays. We used bioinformatic tools to assess the link between SLC35A2 expression and immune infiltration, and performed immunohistochemistry for validation. CCK8, EdU, transwell, flow cytometer, and westernblottingwere used to assess the proliferation, motility, cell cycleand apoptosis of BRCA cells in vitro. The xenograft models were constructed to assess the effect of SLC35A2 on BRCA tumor growth in vivo. The results indicated thatSLC35A2 expression was upregulated and linked to an unfavorable prognosis in BRCA. The most likely upstream ncRNA‐associated pathway of SLC35A2 in BRCA was the AC074117.1/hsa‐let‐7b‐5p axis. SLC35A2 expression had positive correlations with the presence of Th2 cells, regulatory T cells, and immune checkpoints. Knockdown ofSLC35A2could reduce BRCA cell proliferation, motility, and cause G2/M arrest and cell apoptosis via ERK signaling. Moreover, ERK activation can rescue the inhibitory effects of knockdownSLC35A2in BRCA. In conclusion, AC074117.1/hsa‐let‐7b‐5p axis‐mediated high expression of SLC35A2 acts as a tumor promoter in BRCA via ERK signaling, which provides a potential target for BRCA treatment.