KMT2B promotes SHPRH expression to regulate I-131 sensitivity in thyroid carcinoma cells by affecting FYN protein stability
KMT2B promotes SHPRH expression to regulate I-131 sensitivity in thyroid carcinoma cells by affecting FYN protein stability
复制标题
KMT2B通过影响FYN蛋白稳定性促进SHPRH表达调节甲状腺癌细胞I-131敏感性
DOI：
10.1016/j.cellsig.2021.110165
复制
发表时间：
2021
影响因子：
4.8
通讯作者：
Huang Da
中科院分区：
文献类型：
--
作者：
Chen Wanzhi;Zhong Meijun;Yu Jichun;Xie Rong;Zhou Tao;Zhang Shuyong;Xiong Chengfeng;Huang Da
Radioiodine (131I) is one of the most well-known and widely used targeted therapies. In thyroid carcinoma (THCA), it has been applied for more than eight decades and is still being utilized to eliminate remnants after resection and to reduce tumor metastases. Here, we aimed to investigate if lysine methyltransferase 2B (KMT2B) silencing could confer131I resistance to THCA cells and the epigenetic mechanism behind. RT-qPCR, immunohistochemistry and western blot revealed that KMT2B was poorly expressed in THCA cells, and131I resistance of cells led to a further decrease in KMT2B expression. EdU, colony formation, TUNEL, and tumor growth and metastasis assays showed that overexpression of KMT2B sensitized THCA cell to131I and inhibited cell growth and metastasis. Further bioinformatics prediction and functional assay validation revealed that KMT2B elevated SHPRH expressionviaH3K4me3 modification in the SHPRH promoter, and that SHPRH modulated FYN ubiquitination, thereby promoting its protein degradation. We finally proved that the131I-resistant cells regained resistance to131I by FYN overexpression in the presence of KMT2B overexpressionin vitroandin vivo. Therefore, we conclude that the overexpression of KMT2B represents a potential target for THCA therapy.
