1. Academic Validation
  2. FoxM1 promotes the migration of ovarian cancer cell through KRT5 and KRT7

FoxM1 promotes the migration of ovarian cancer cell through KRT5 and KRT7

  • Gene. 2020 Oct 5;757:144947. doi: 10.1016/j.gene.2020.144947.
Ziyu Zhang 1 Kaijia Tu 2 Faying Liu 1 Meirong Liang 2 Kaihui Yu 3 Yaoqing Wang 3 Yong Luo 1 Bicheng Yang 1 Yunna Qin 4 Deming He 4 Guoyi Jiang 5 Ouping Huang 6 Yang Zou 7
Affiliations

Affiliations

  • 1 Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, PR China; Central Laboratory, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, PR China.
  • 2 Department of Oncology, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, PR China.
  • 3 The College of Medicine, Nanchang University, Nanchang, Jiangxi 330006, PR China.
  • 4 Department of Pathology, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, PR China.
  • 5 Department of Obstetrics, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi, 330006, PR China.
  • 6 Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, PR China; Central Laboratory, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, PR China. Electronic address: jxhop59@126.com.
  • 7 Key Laboratory of Women's Reproductive Health of Jiangxi, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, PR China; Central Laboratory, Jiangxi Maternal and Child Health Hospital, Nanchang, Jiangxi 330006, PR China. Electronic address: zouyang81@163.com.
Abstract

Forkhead box M1(FoxM1) played an important role in the pathogenesis of ovarian Cancer, but its downstream molecular network is mysterious. Here, we combined ChIP-seq with RNA-seq analysis and identified 687 FoxM1-binding regions and 182 genes regulated by FoxM1. The above data pointed out that KRT5 and KRT7 were downstream target genes of FoxM1. Next, we used qPCR and Western blot to verify that FoxM1 knockdown inhibited the expression levels of KRT5 and KRT7. We also demonstrated that FoxM1 regulated KRT5 and KRT7 genes expression through binding a consensus AP-2 cis element, and showed that KRT5 and KRT7 deficiency could prevent the migration but not proliferation of SK-OV-3 cells. Finally, tissue microarray results indicated that KRT5 and KRT7 were highly expressed in ovarian Cancer and positively correlated with FoxM1 expression. TCGA database showed that high expression of KRT5 and KRT7 could significantly reduce the survival rate of patients with ovarian Cancer. The above results clarify the specific downstream molecular network of FoxM1 to promote the pathogenesis of ovarian Cancer, and provide a basis experiment for the judgment of ovarian Cancer prognosis and the design of drug targets.

Keywords

ChIP-seq; FoxM1; KRT proteins; Ovarian cancer; RNA-seq.

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