Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Rd., Yangfangdian, Haidian District, Beijing 100038, PR China.
Department of Neurosurgery, Beijing Shijitan Hospital, Capital Medical University, No. 10 Tieyi Rd., Yangfangdian, Haidian District, Beijing 100038, PR China.
Biomed Pharmacother. 2018 Mar;99:72-80. doi: 10.1016/j.biopha.2018.01.020. Epub 2018 Jan 8.
Malignant gliomas are highly lethal cancers worldwide as tumor cells infiltrate to healthy brain tissue invariably. Histone demethylase KDM5A as an oncogene or tumor suppressor in cancer still has been controversial. KDM5A may have a different function in different type cancer cells. However, the specific roles of KDM5A in the progression of glioma remain undiscovered. In this study, we found that compared with primary glioma, metastasis glioma had low KDM5A levels. Besides, lower KDM5A levels were linked to poor survival in glioma cancer patients, indicating that KDM5A is a new prognostic marker for glioma cancer. KDM5A knockdown increases the invasive abilities of glioma cancer cells and changes the EMT markers. A mechanism, KDM5A suppressing the expression of ZEB1, and its catalytic activity is indispensable for anti-invasive function. Our study revealed that histone demethylase KDM5A exerts anti-invasiveness function partly through repressing oncogenic ZEB1 expression by mediating H3K4 demethylation. We also demonstrate that ZEB1 play a crucial role in KDM5A induced function. In summary, in this study, we showed that KDM5A has a crucial role in glioma and therefore may serve as a novel therapeutic target and prognostic marker in glioma.
恶性胶质瘤是全球范围内高度致命的癌症，因为肿瘤细胞总是浸润到健康的脑组织中。组蛋白去甲基化酶 KDM5A 作为癌基因或抑癌基因在癌症中的作用仍存在争议。KDM5A 在不同类型的癌细胞中可能具有不同的功能。然而，KDM5A 在胶质瘤进展中的具体作用仍未被发现。在这项研究中，我们发现与原发性胶质瘤相比，转移性胶质瘤的 KDM5A 水平较低。此外，KDM5A 水平较低与胶质瘤患者的生存预后不良相关，表明 KDM5A 是一种新的胶质瘤预后标志物。KDM5A 敲低会增加胶质瘤癌细胞的侵袭能力，并改变 EMT 标志物。一种机制是，KDM5A 通过抑制致癌基因 ZEB1 的表达及其催化活性来发挥抗侵袭功能。我们的研究表明，组蛋白去甲基化酶 KDM5A 通过介导 H3K4 去甲基化来部分发挥抗侵袭功能，抑制致癌基因 ZEB1 的表达。我们还证明 ZEB1 在 KDM5A 诱导的功能中起着关键作用。总之，在这项研究中，我们表明 KDM5A 在胶质瘤中具有重要作用，因此可能成为胶质瘤的新型治疗靶点和预后标志物。
