Ling Jing, Dong Xiao, Wang Lei, Xue Ying, Jia Xuebing, Song Weifeng, Li Qi
Department of Oncology, Shanghai General Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai 200080, China.
Shanghai Key Laboratory of Pancreatic Diseases Shanghai 200080, China.
Am J Transl Res. 2019 May 15;11(5):3069-3080. eCollection 2019.
FOXO1, also known as FKHR, is a member of the Forkhead transcription factor family. Our previous study revealed that FOXO1 expression is significantly downregulated in pancreatic ductal adenocarcinoma (PDAC). However, our knowledge on the clinical significance of FOXO1 and its biological roles and associated mechanisms in PDAC tumorigenesis remains limited. In this study, we confirmed that FOXO1 is commonly downregulated in PDAC tissues, at both the mRNA and protein levels, compared to adjacent tissues. Furthermore, FOXO1 inhibited cell proliferation and tumor formation both and , and promoted pancreatic cancer cell invasion. Downregulation of FOXO1 resulted in enhanced Wnt/β-catenin signaling activity, thereby promoting cell proliferation and epithelial-mesenchymal transition. The highly expressed miR-27a could potentially be used to target the 3'-UTR of FOXO1 in PDAC tissues to inhibit or at least slow down the invasion and proliferation of cancerous cells. Taken together, our findings suggest that the miR-27a/FOXO1/β-catenin axis may serve as a promising therapeutic target in PDAC progression.
叉头框蛋白O1（FOXO1），也称为叉头转录因子FKHR，是叉头转录因子家族的成员。我们之前的研究表明，FOXO1在胰腺导管腺癌（PDAC）中的表达显著下调。然而，我们对FOXO1在PDAC肿瘤发生中的临床意义、生物学作用及相关机制的了解仍然有限。在本研究中，我们证实与相邻组织相比，FOXO1在PDAC组织中的mRNA和蛋白质水平均普遍下调。此外，FOXO1在体内和体外均抑制细胞增殖和肿瘤形成，并促进胰腺癌细胞侵袭。FOXO1的下调导致Wnt/β-连环蛋白信号活性增强，从而促进细胞增殖和上皮-间质转化。高表达的miR-27a可能用于靶向PDAC组织中FOXO1的3'-非翻译区，以抑制或至少减缓癌细胞的侵袭和增殖。综上所述，我们的研究结果表明，miR-27a/FOXO1/β-连环蛋白轴可能是PDAC进展中一个有前景的治疗靶点。
