Histone demethylase KDM5A inhibits glioma cells migration and invasion by down regulating ZEB1.

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.