Interleukin-1 receptor-associated kinase 1 correlates with metastasis and invasion in endometrial carcinoma

Endometrial carcinoma (EC) is one of the most common malignancies in the world. Previous studies have investigated the altered expression of interleukin-1 receptor-associated kinase 1 (IRAK1) in various cancers. We aimed at exploring the biological function and the underlying molecular mechanism of IRAK1 in EC. In this study, IRAK1 was found elevated in EC compared with normal tissues. Further, high IRAK1 expression level was correlated with higher tumor stage, lymph node metastasis, myometrial invasion, and lower survival rate. Knockdown of IRAK1 in two EC cell lines, HEC-1-B and JEC, significantly inhibited cell proliferation in vitro and in vivo. We also found that down-regulation of IRAK1 in EC cells notably induced cell cycle arrest and apoptois, and also inhibited cell migration and invasion. Gene set enrichment analysis on The Cancer Genome Atlas dataset showed that Kyoto Encyclopedia of Genes and Genomes (KEGG) mitotic cell cycle and cell division pathways were correlative with the IRAK1 expression, which was further confirmed in EC cells by Western blot. The expression of mitotic cell cycle (CDK1 and Cdc45) and cell division pathway (Cdc7 and MCM2) related factors was significantly suppressed by IRAK1 knockdown. These collective data indicated that IRAK1 overexpression promotes EC tumorigenesis by activating mitotic cell cycle and cell division pathways, and IRAK1 may serve as a promising therapeutic strategy for EC.