Iravani Omid, Bay Boon-Huat, Yip George Wai-Cheong
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Exp Cell Res. 2017 Jan 15;350(2):380-389. doi: 10.1016/j.yexcr.2016.12.019. Epub 2016 Dec 23.
Heparan sulfate 6-O-sulfation is biologically edited by 6-O-sulfotransferases (HS6STs) within heparan sulfate chains. Three isoforms of HS6ST have been identified. These enzymes are found to be differentially expressed in a variety of tissues. Recently, several studies have shown that dysregulation of 6-O-sulfotransferases could be involved in tumorigenesis of several cancers. This study aimed to analyze the expression and function of HS6ST3 in breast cancer. HS6ST3 was found up-regulated in T47D, MCF7 and MDA-MB231 breast cancer cell lines. HS6ST3 was then silenced in T47D and MCF7 using siRNA. Silencing HS6ST3 diminished tumor cell growth, migration and invasion, but enhanced cell adhesion and apoptosis in breast cancer. Gene microarray analysis revealed that silencing HS6ST3 significantly changed the expression of IGF1R and XAF1 in breast cancer cells. Further functional studies showed that the cellular processes were mediated by IGF1R and XAF1 after silencing HS6ST3 in breast cancer cells. Together these results indicate that HS6ST3 might be involved in the tumorigenesis of breast cancer and it could be a promising target in breast cancer therapy.
硫酸乙酰肝素6 - O - 硫酸化在硫酸乙酰肝素链内由6 - O - 硫酸转移酶（HS6STs）进行生物学编辑。已鉴定出HS6ST的三种同工型。这些酶在多种组织中差异表达。最近，多项研究表明6 - O - 硫酸转移酶的失调可能与多种癌症的肿瘤发生有关。本研究旨在分析HS6ST3在乳腺癌中的表达及功能。在T47D、MCF7和MDA - MB231乳腺癌细胞系中发现HS6ST3上调。随后使用小干扰RNA（siRNA）使T47D和MCF7中的HS6ST3沉默。沉默HS6ST3可减少乳腺癌细胞的生长、迁移和侵袭，但增强细胞黏附及凋亡。基因微阵列分析显示，沉默HS6ST3显著改变了乳腺癌细胞中IGF1R和XAF1的表达。进一步的功能研究表明，在乳腺癌细胞中沉默HS6ST3后，细胞过程由IGF1R和XAF1介导。这些结果共同表明，HS6ST3可能参与乳腺癌的肿瘤发生，并且它可能是乳腺癌治疗中有前景的靶点。
