Epigenetic Regulation of the Biosynthesis & Enzymatic Modification of Heparan Sulfate Proteoglycans: Implications for Tumorigenesis and Cancer Biomarkers.
Epigenetic Regulation of the Biosynthesis & Enzymatic Modification of Heparan Sulfate Proteoglycans: Implications for Tumorigenesis and Cancer Biomarkers.
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DOI：
10.3390/ijms18071361
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发表时间：
2017-06-26
影响因子：
5.6
通讯作者：
Leyva KJ
中科院分区：
文献类型：
--
作者：
Hull EE;Montgomery MR;Leyva KJ
新的证据表明，硫酸乙酰肝素蛋白多糖(HSPGs)生物合成途径中的酶在多个水平上受表观遗传调控。由于HSPG分子中硫酸乙酰肝素部分的确切组成对肿瘤发生的广泛生物学过程至关重要，因此，硫酸乙酰肝素生物合成的表观遗传调控对许多与癌症进展相关的细胞活动具有深远的影响。鉴于目前的重点是开发以表观遗传学为靶点的新的抗癌疗法，了解这些新兴疗法可能对HSPG的合成产生的影响是重要的，因为HSPG组成的改变可能会产生深远的和意想不到的影响。作为引言，本文将简要总结HSPGs在与癌症相关的广泛细胞和生理功能中发挥的各种重要作用，然后描述HSPGs的硫酸乙酰肝素链的生物合成，包括在癌细胞中观察到的变化如何作为潜在的生物标记物。这篇综述将集中于硫酸乙酰肝素合成途径中酶的多个水平的表观遗传调节，特别是通过miRNA的调节和表观遗传疗法对HSPGs的影响。我们还将探索使用凝集素来检测硫酸肝素组成的差异，并展望其在临床上的潜在诊断和预后用途。
Emerging evidence suggests that the enzymes in the biosynthetic pathway for the synthesis of heparan sulfate moieties of heparan sulfate proteoglycans (HSPGs) are epigenetically regulated at many levels. As the exact composition of the heparan sulfate portion of the resulting HSPG molecules is critical to the broad spectrum of biological processes involved in oncogenesis, the epigenetic regulation of heparan sulfate biosynthesis has far-reaching effects on many cellular activities related to cancer progression. Given the current focus on developing new anti-cancer therapeutics focused on epigenetic targets, it is important to understand the effects that these emerging therapeutics may have on the synthesis of HSPGs as alterations in HSPG composition may have profound and unanticipated effects. As an introduction, this review will briefly summarize the variety of important roles which HSPGs play in a wide-spectrum of cancer-related cellular and physiological functions and then describe the biosynthesis of the heparan sulfate chains of HSPGs, including how alterations observed in cancer cells serve as potential biomarkers. This review will then focus on detailing the multiple levels of epigenetic regulation of the enzymes in the heparan sulfate synthesis pathway with a particular focus on regulation by miRNA and effects of epigenetic therapies on HSPGs. We will also explore the use of lectins to detect differences in heparan sulfate composition and preview their potential diagnostic and prognostic use in the clinic.
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DOI：
10.1016/j.bbrc.2012.08.140
发表时间：
2012-10-05
影响因子：
3.1
作者：
Choi, Hee-Jung;Chung, Tae-Wook;Ha, Ki-Tae
通讯作者：
Ha, Ki-Tae
影响因子：
6.9
作者：
Christianson, Helena C.;Belting, Mattias
通讯作者：
Belting, Mattias
影响因子：
--
作者：
Ceroni A;Dell A;Haslam SM
通讯作者：
Haslam SM
DOI：
10.1083/jcb.200404171
发表时间：
2004-10-11
期刊：
The Journal of cell biology
影响因子：
--
作者：
Beauvais DM;Burbach BJ;Rapraeger AC
通讯作者：
Rapraeger AC
影响因子：
--
作者：
Cassinelli G;Favini E;Dal Bo L;Tortoreto M;De Maglie M;Dagrada G;Pilotti S;Zunino F;Zaffaroni N;Lanzi C
通讯作者：
Lanzi C