抑制透明质酸降解途径可通过诱导凋亡和细胞周期阻滞来抑制胶质瘤进展。
Inhibition of hyaluronic acid degradation pathway suppresses glioma progression by inducing apoptosis and cell cycle arrest.
作者信息
Yan Tao, Yang He, Xu Caixia, Liu Junsi, Meng Yun, Jiang Qing, Li Jinxing, Kang Guiqiong, Zhou Liangjian, Xiao Shuai, Xue Yanpeng, Xu Jiayi, Chen Xin, Che Fengyuan
机构信息
Central Laboratory, Linyi People's Hospital, Guangzhou University of Chinese Medicine, Linyi, 276000, Shandong Province, China.
Linyi Key Laboratory of Neurophysiology, Linyi People's Hospital, Linyi, 276000, Shandong Province, China.
出版信息
Cancer Cell Int. 2023 Aug 11;23(1):163. doi: 10.1186/s12935-023-02998-4.
BACKGROUND
Abnormal hyaluronic acid (HA) metabolism is a major factor in tumor progression, and the metabolic regulation of HA mainly includes HA biosynthesis and catabolism. In glioma, abnormal HA biosynthesis is intimately involved in glioma malignant biological properties and the formation of immunosuppressive microenvironment; however, the role of abnormal HA catabolism in glioma remains unclear.
METHODS
HA catabolism is dependent on hyaluronidase. In TCGA and GEPIA databases, we found that among the 6 human hyaluronidases (HYAL1, HYAL2, HYAL3, HYAL4, HYALP1, SPAM1), only HYAL2 expression was highest in glioma. Next, TCGA and CGGA database were further used to explore the correlation of HYAL2 expression with glioma prognosis. Then, the mRNA expression and protein level of HYAL2 was determined by qRT-PCR, Western blot and Immunohistochemical staining in glioma cells and glioma tissues, respectively. The MTT, EdU and Colony formation assay were used to measure the effect of HYAL2 knockdown on glioma. The GSEA enrichment analysis was performed to explore the potential pathway regulated by HYAL2 in glioma, in addition, the HYAL2-regulated signaling pathways were detected by flow cytometry and Western blot. Finally, small molecule compounds targeting HYAL2 in glioma were screened by Cmap analysis.
RESULTS
In the present study, we confirmed that Hyaluronidase 2 (HYAL2) is abnormally overexpressed in glioma. Moreover, we found that HYAL2 overexpression is associated with multiple glioma clinical traits and acts as a key indicator for glioma prognosis. Targeting HYAL2 could inhibit glioma progression by inducing glioma cell apoptosis and cell cycle arrest.
CONCLUSION
Collectively, these observations suggest that HYAL2 overexpression could promote glioma progression. Thus, treatments that disrupt HA catabolism by altering HYAL2 expression may serve as effective strategies for glioma treatment.
背景
透明质酸（HA）代谢异常是肿瘤进展的主要因素，HA的代谢调节主要包括HA生物合成和分解代谢。在胶质瘤中，异常的HA生物合成与胶质瘤的恶性生物学特性及免疫抑制微环境的形成密切相关；然而，异常的HA分解代谢在胶质瘤中的作用仍不清楚。
方法
HA分解代谢依赖于透明质酸酶。在TCGA和GEPIA数据库中，我们发现，在6种人类透明质酸酶（HYAL1、HYAL2、HYAL3、HYAL4、HYALP1、SPAM1）中，只有HYAL2在胶质瘤中的表达最高。接下来，进一步利用TCGA和CGGA数据库探讨HYAL2表达与胶质瘤预后的相关性。然后，分别通过qRT-PCR、Western blot和免疫组织化学染色检测胶质瘤细胞和胶质瘤组织中HYAL2的mRNA表达和蛋白水平。采用MTT、EdU和集落形成试验检测敲低HYAL2对胶质瘤的影响。进行GSEA富集分析以探索HYAL2在胶质瘤中调节的潜在通路，此外，通过流式细胞术和Western blot检测HYAL2调节的信号通路。最后，通过Cmap分析筛选胶质瘤中靶向HYAL2的小分子化合物。
结果
在本研究中，我们证实透明质酸酶2（HYAL2）在胶质瘤中异常高表达。此外，我们发现HYAL2的过表达与多种胶质瘤临床特征相关，并作为胶质瘤预后的关键指标。靶向HYAL2可通过诱导胶质瘤细胞凋亡和细胞周期停滞来抑制胶质瘤进展。
结论
总的来说，这些观察结果表明HYAL2的过表达可促进胶质瘤进展。因此，通过改变HYAL2表达来破坏HA分解代谢的治疗方法可能是胶质瘤治疗的有效策略。
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