Transcription factor LIM1 progresses tumor growth in endometrial cancer via CREB signaling.

The incidence of endometrial cancer (EC) is increasing worldwide, however, therapeutic options for EC are limited and novel therapeutic targets for EC are required. We reanalyzed RNA-seq data of EC registered in The Cancer Genome Atlas and found significant upregulation of transcription factor LIM homeobox1 (LIM1) in stages II-IV compared to stage I of EC patients. LIM1-knocked down (LIM1-KD) and Control sublines were established using HEC50B cell line and then RNA-sequence results were analyzed by Ingenuity pathway analysis (IPA). It revealed enrichment of CREB signaling-related genes among differentially expressed genes between Control and LIM1-KD sublines. Also, decreased levels of phosphorylated CREB were observed in LIM1-KD subline. In the Xenograft model used by HEC50B sublines, tumor growth was significantly suppressed in the LIM1-KD subline compared to Control subline. Immunofluorescent staining showed decreased phosphorylation of CREB in LIM1-KD-derived tumors. Kaplan-Meier plotter analysis indicated that the high LIM1 expression group had a significantly poorer prognosis. These results suggest that LIM1 in EC progresses tumor growth and malignancy via CREB signaling. mRNA profiles of HEC50B cell line that stably express LIM1 shRNA and control shRNA obtained by deep sequencing using illumina NextSeq 500.