FOXM1 as a prognostic biomarker promotes endometrial cancer progression via transactivation of SLC27A2 expression.

ABSTRACT

Endometrial cancer (EC) is one of the most important gynecological cancers, but its pathogenesis is not clearly understood, and it also lacks an effective treatment. The nuclear transcriptional protein forkhead box protein M1 (FOXM1) has crucial functions in the development and progression of cancer and is treated as a prognostic biomarker and therapeutic target in many types of cancers. However, the situation and underlying mechanisms of FOXM1's involvement in EC is largely underestimated. In our present study, we found FOXM1 was overexpressed in EC, including endometrioid (EEC) and serous (SEC). High expression of FOXM1 was meaningfully associated with a poor prognosis of EC patients as well as with EC pathological stages and clinical grades. Knocking down FOXM1 could significantly reduce the proliferation and migration capacity of AN3CA and ISHIKAWA cells. Furthermore, our RNA-seq results indicated that the knockdown of FOXM1 mainly affects downstream metabolic genes in EC cells. Finally, we also discovered one potential functional pathway, FOXM1-SLC27A2, which may contribute to EC progression. Taken together, the high expression of FOXM1 is closely associated with the prognosis, pathological stages, and clinical grades of EC patients. FOXM1 can promote the proliferation and migration of EC cells. Through SLC27A2, FOXM1 may influence the metabolic activity of EC cells, and FOXM1-SLC27A signaling could be treated as a potential cellular target for a therapeutic strategy of EC.