AUTHOR=Kato Hiroaki , Saeki Noritaka , Imai Matome , Onji Hiroshi , Yano Akiko , Yoshida Shuhei , Sakaue Tomohisa , Fujioka Toru , Sugiyama Takashi , Imai Yuuki 

TITLE=LIM1 contributes to the malignant potential of endometrial cancer

JOURNAL=Frontiers in Oncology

VOLUME=Volume 13 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2023.1082441

DOI=10.3389/fonc.2023.1082441

ISSN=2234-943X

ABSTRACT=The incidence of endometrial cancer (EC) has been increasing worldwide. However, because there are limited chemotherapeutic options for the treatment of EC, the prognosis of advanced-stage EC is poor. To identify therapeutic targets, we analyzed gene expression profile datasets for EC cases registered in The Cancer Genome Atlas. Highly expressed genes in advanced-stage EC (110 cases) compared with early-stage EC (255 cases) were extracted and enriched with homeobox genes by Gene Ontology enrichment analysis. Among the identified genes, Kaplan-Meier plotter analysis of patients with EC showed that high LIM homeobox1 (LIM1) expression was associated with a significantly poorer prognosis. Additionally, LIM1 expression was significantly upregulated in high-grade EC cell lines (HEC50B cells). Knockdown of LIM1 in LIM1-knockdown (KD) HEC50B cells showed reduced cell proliferation and invasion. Ingenuity Pathway Analysis of RNA-seq data using LIM-KD cells revealed that the expression of CREB signaling-related genes was significantly suppressed and that phosphorylation of CREB was decreased in LIM1-KD cells. Furthermore, xenograft experiments revealed that tumor growth was significantly suppressed when CREB phosphorylation was decreased in LIM1-KD-derived tumors. Collectively, these results suggested that high LIM1 expression contributed to tumor growth via CREB signaling in EC.