Interfering with hyaluronic acid metabolism suppresses glioma cell proliferation by regulating autophagy.
Interfering with hyaluronic acid metabolism suppresses glioma cell proliferation by regulating autophagy.
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干扰透明质酸代谢通过调节自噬抑制神经胶质瘤细胞增殖
DOI：
10.1038/s41419-021-03747-z
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发表时间：
2021-05-13
影响因子：
9
通讯作者：
Zhao S
中科院分区：
文献类型：
--
作者：
Yan T;Chen X;Zhan H;Yao P;Wang N;Yang H;Zhang C;Wang K;Hu H;Li J;Sun J;Dong Y;Lu E;Zheng Z;Zhang R;Wang X;Ma J;Gao M;Ye J;Wang X;Teng L;Liu H;Zhao S
肿瘤微环境在肿瘤进展中起着重要作用。透明质酸（HA）是肿瘤微环境中细胞外基质的重要成分，在多种肿瘤中异常蓄积。然而，异常HA积聚在胶质瘤中的作用仍不清楚。本研究表明，HA、透明质酸合成酶3（HAS 3）及其受体CD 44在人脑胶质瘤组织中高水平表达，并与胶质瘤患者的预后呈负相关。在体外和体内，沉默HAS 3表达或阻断CD 44抑制胶质瘤细胞增殖。其作用机制可能与抑制胶质瘤细胞自噬流，使胶质瘤细胞周期阻滞于G1期有关。更重要的是，4-甲基伞形酮（4-MU），尿苷二磷酸（UDP）的一个小的竞争性抑制剂，具有穿透血脑屏障（BBB）的能力，也抑制胶质瘤细胞增殖在体外和体内。因此，通过改变HAS 3和CD 44的表达和施用4-MU来干扰HA代谢的方法可能代表神经胶质瘤治疗的有效策略。
The tumor microenvironment plays an important role in tumor progression. Hyaluronic acid (HA), an important component of the extracellular matrix in the tumor microenvironment, abnormally accumulates in a variety of tumors. However, the role of abnormal HA accumulation in glioma remains unclear. The present study indicated that HA, hyaluronic acid synthase 3 (HAS3), and a receptor of HA named CD44 were expressed at high levels in human glioma tissues and negatively correlated with the prognosis of patients with glioma. Silencing HAS3 expression or blocking CD44 inhibited glioma cell proliferation in vitro and in vivo. The underlying mechanism was attributed to the inhibition of autophagy flux and maintaining glioma cell cycle arrest in G1 phase. More importantly, 4-methylumbelliferone (4-MU), a small competitive inhibitor of Uridine diphosphate (UDP) with the ability to penetrate the blood-brain barrier (BBB), also inhibited glioma cell proliferation in vitro and in vivo. Thus, approaches that interfere with HA metabolism by altering the expression of HAS3 and CD44 and the administration of 4-MU potentially represent effective strategies for glioma treatment.
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影响因子：
29
作者：
Kimmelman AC;White E
通讯作者：
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作者：
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