The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, PR China.
Department of Plastic and Reconstructive Surgery, Huashan Hospital, Fudan University School of Medicine, Shanghai, 200040, PR China.
Mol Cell Endocrinol. 2019 Aug 1;493:110420. doi: 10.1016/j.mce.2019.03.010. Epub 2019 May 23.
Forkhead box E1 (FOXE1) plays an important role in the development, proliferation and differentiation of thyroid cells. However, the biological functions of FOXE1 in papillary thyroid cancer (PTC) remain unclear.
In this study, the level of FOXE1 expression was examined in human PTC tissues and cells. Then, the high expression of FOXE1 was specifically silenced by RNA interference in vitro. Subsequently, FOXE1-shRNA was transfected into PTC cells (TPC-1 and K1). The effects on cell proliferation, migration and invasion were evaluated. In addition, FOXE1 targets were screened by cDNA microarray assays. The correlation between the expression of target gene platelet-derived growth factor A (PDGFA) and clinicopathological features of PTC patients was analysed.
FOXE1 is highly expressed in PTC tissues and PTC cell lines. The silencing of FOXE1 significantly promotes PTC cell proliferation, migration and invasion in vitro. The cDNA microarray analyses show that PDGFA is a critical downstream target gene of FOXE1 in PTC cells. It was also observed that PDGFA is negatively regulated by FOXE1 in PTC. The clinical data indicate that the low expression level of PDGFA is correlated with the small size of PTC.
Collectively, the results indicate for the first time that high expression of FOXE1 may function as a tumour suppressor in the early stage of PTC and restrain the proliferation, migration and invasion of PTC by negatively regulating PDGFA expression. Thus, FOXE1 could serve as a prognostic biomarker for PTC.
叉头框转录因子 E1(FOXE1)在甲状腺细胞的发育、增殖和分化中发挥重要作用。然而,FOXE1 在甲状腺乳头状癌(PTC)中的生物学功能尚不清楚。
本研究检测了 FOXE1 在人 PTC 组织和细胞中的表达水平。然后,通过体外 RNA 干扰特异性沉默 FOXE1 的高表达。随后,将 FOXE1-shRNA 转染至 PTC 细胞(TPC-1 和 K1)中。评估其对细胞增殖、迁移和侵袭的影响。此外,通过 cDNA 微阵列分析筛选 FOXE1 的靶基因。分析靶基因血小板衍生生长因子 A(PDGFA)的表达与 PTC 患者临床病理特征的相关性。
FOXE1 在 PTC 组织和 PTC 细胞系中高表达。FOXE1 的沉默显著促进了 PTC 细胞的体外增殖、迁移和侵袭。cDNA 微阵列分析表明,PDGFA 是 PTC 细胞中 FOXE1 的关键下游靶基因。研究还发现 PDGFA 受 FOXE1 的负调控。临床数据表明,PDGFA 的低表达水平与 PTC 的体积小有关。
综上所述,这些结果首次表明,FOXE1 的高表达可能在 PTC 的早期阶段作为肿瘤抑制因子发挥作用,并通过负调控 PDGFA 的表达抑制 PTC 的增殖、迁移和侵袭。因此,FOXE1 可作为 PTC 的预后标志物。