KDM1A promotes thyroid cancer progression and maintains stemness through the Wnt/β-catenin signaling pathway
Wei Zhang, Xianhui Ruan, Yaoshuang Li, Jingtai Zhi, Linfei Hu, Xiukun Hou, Xianle Shi, Xin Wang, Jinpeng Wang, Weike Ma, Pengfei Gu, Xiangqian Zheng, Ming Gao
Abstract
Background: Cancer stem cells (CSCs) are highly tumorigenic, chemotherapy-resistant, tumor growth-sustaining, and are implicated in tumor recurrence. Previous studies have shown that lysine-specific histone demethylase 1A (KDM1A) is highly expressed in several human malignancies and CSCs. However, the role of KDM1A in CSCs and the therapeutic potential of KDM1A inhibitors for the treatment of the advanced thyroid cancer are poorly understood. Methods: Firstly, KDM1A was identified as an important epigenetic modifier that maintained the stemness of thyroid cancer through a mini histone methylation modifier screen and confirmed in thyroid cancer tissues and cell lines. RNA sequence was performed to discover the downstream genes of KDM1A. The underlying mechanisms were further investigated by ChIP, IP and dual luciferase reporter assays, gain and loss of function assays.