FOXA1-mediated transcription of MFAP2 facilitates cell growth, metastasis and cisplatin resistance in uterine corpus endometrial carcinoma.

Microfibril-associated protein 2 (MFAP2) has been confirmed to be an oncogene to participate in regulating the progression of many cancers. However, its role and mechanism in the development of uterine corpus endometrial carcinoma (UCEC) are still unclear. The mRNA and protein levels of MFAP2 and forkhead box A1 (FOXA1) were determined using qRT-PCR and western blot. Cell proliferation, apoptosis, migration, invasion and cisplatin resistance were detected by colony formation assay, EdU assay, flow cytometry, transwell assay and CCK8 assay. Xenograft tumor models were constructed to explore the effect of MFAP2 knockdown on UCEC tumorigenesis and cisplatin resistance in vivo. The interaction between FOXA1 and MFAP2 promoter was evaluated by ChIP assay and dual-luciferase reporter assay. MFAP2 was upregulated in UCEC tissues and cells. Silencing of MFAP2 repressed UCEC cell growth, metastasis and cisplatin resistance in vitro, as well as reduced tumorigenesis in vivo. In terms of mechanism, FOXA1 bound to MFAP2 promoter region to increase its expression. FOXA1 knockdown could inhibit UCEC cell growth, metastasis and cisplatin resistance. Moreover, FOXA1 promoted growth, metastasis and cisplatin resistance in UCEC cells via enhancing MFAP2 expression. FOXA1-activated MFAP2 might contribute to the growth, metastasis and cisplatin resistance of UCEC cells, providing a novel target for UCEC treatment.