Transcription factor SP1 regulates haptoglobin fucosylation via induction of GDP-fucose transporter 1 in the hepatoma cell line HepG2

Jumpei Kondo; Natsumi Sakata; Koichi Morishita; Ayumu Hayashibara; Daisuke Sakon; Shinji Takamatsu; Nobuhiko Asakura; Takashi Suzuki; Eiji Miyoshi

doi:10.1016/j.bbrep.2022.101372

Transcription factor SP1 regulates haptoglobin fucosylation via induction of GDP-fucose transporter 1 in the hepatoma cell line HepG2

Biochem Biophys Rep. 2022 Oct 25:32:101372. doi: 10.1016/j.bbrep.2022.101372. eCollection 2022 Dec.

Authors

Jumpei Kondo¹, Natsumi Sakata¹, Koichi Morishita¹, Ayumu Hayashibara¹, Daisuke Sakon¹, Shinji Takamatsu¹, Nobuhiko Asakura², Takashi Suzuki², Eiji Miyoshi¹

Affiliations

¹ Department of Molecular Biochemistry and Clinical Investigation, Osaka University Graduate School of Medicine, 1-7 Yamada-oka, Suita, Osaka, 565-0871, Japan.
² Center for Mathematical Modeling and Data Science, Osaka University, 1-3 Machikaneyama, Toyonaka, Osaka, 560-8531, Japan.

Abstract

Fucosylation is involved in cancer and inflammation, and several fucosylated proteins, such as AFP-L3 for hepatocellular carcinoma, are used as cancer biomarkers. We previously reported an increase in serum fucosylated haptoglobin (Fuc-Hp) as a biomarker for several cancers, including pancreatic and colon cancer and hepatocellular carcinoma. The regulation of fucosylated protein production is a complex cellular process involving various fucosylation regulatory genes. In this report, we investigated the molecular mechanisms regulating Fuc-Hp production in cytokine-treated hepatoma cells using a partial least squares (PLS) regression model. We found that SLC35C1, which encodes GDP-fucose transporter 1 (GFT1), is the most responsible factor for Fuc-Hp production among various fucosylation regulatory genes. Furthermore, the transcription factor SP1 was essential in regulating SLC35C1 expression. We also found that an SP1 inhibitor was able to suppress Fuc-Hp production without affecting total Hp levels. Taken together, Fuc-Hp production was regulated by SP1 via induction of GFT1 in the hepatoma cell line HepG2.

Keywords: Cancer biomarker; Fucosylation; GDP, Guanosine diphosphate; GDP-Fucose transporter 1 (GFT1); Haptoglobin; Solute carrier family 35 member C1(SLC35C1); Specificity protein 1 (SP1).