Transcriptional Regulation of Siglec-15 by ETS-1 and ETS-2 in Hepatocellular Carcinoma Cells

被引：8

作者：

Sheng, Kaiqin ^{[1
]}

Wu, Yuecheng ^{[1
]}

Lin, Hanbin ^{[1
]}

Fang, Menghan ^{[1
]}

Xue, Chaorong ^{[1
]}

Lin, Xu ^{[1
,2
]}

Lin, Xinjian ^{[1
]}

机构：

[1] Fujian Med Univ, Key Lab Gastrointestinal Canc, Minist Educ, Fuzhou 350122, Peoples R China

[2] Fujian Med Univ, Dept Med Microbiol, Fujian Key Lab Tumor Microbiol, Fuzhou 350122, Peoples R China

来源：

INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES | 2023年 / 24卷 / 01期

基金：

中国国家自然科学基金;

关键词：

Siglec-15; TGF-beta; 1; ETS-1; ETS-2; HCC; transcriptional regulation; CANCER; FAMILY;

D O I：

10.3390/ijms24010792

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) has been identified as a crucial immune suppressor in human cancers, comparable to programmed cell death 1 ligand (PD-L1). However, the regulatory mechanisms underlying its transcriptional upregulation in human cancers remain largely unknown. Here, we show that the transcription factors ETS-1 and ETS-2 bound to the Siglec-15 promoter to enhance transcription and expression of Siglec-15 in hepatocellular carcinoma (HCC) cells and that transforming growth factor beta-1 (TGF-beta 1) upregulated the expression of ETS-1 and ETS-2 and facilitated the binding of ETS-1 and ETS-2 to the Siglec-15 promoter. We further demonstrate that TGF-beta 1 activated the Ras/C-Raf/MEK/ERK1/2 signaling pathway, leading to phosphorylation of ETS-1 and ETS-2, which consequently upregulates the transcription and expression of Siglec-15. Our study defines a detailed molecular profile of how Siglec-15 is transcriptionally regulated which may offer significant opportunity for therapeutic intervention on HCC immunotherapy.

引用

页数：16

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