Xie Haoran, Zhao Qiuyan, Yu Lanting, Lu Jiawei, Peng Kui, Xie Ni, Ni Jianbo, Li Baiwen
Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, New Songjiang Road No. 650, 201620, Shanghai, China; Shanghai Key Laboratory of Pancreatic Diseases, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, New Songjiang Road No. 650, 201620, Shanghai, China.
Department of Gastroenterology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, New Songjiang Road No. 650, 201620, Shanghai, China.
Biochem Biophys Res Commun. 2022 May 21;605:154-161. doi: 10.1016/j.bbrc.2022.03.082. Epub 2022 Mar 17.
There is increasing evidence that circular RNAs (circRNAs) can serve as microRNA (miRNA) sponges to regulate metastasis of multiple tumors, including pancreatic ductal adenocarcinoma (PDAC). However, the role of the circRNA/miRNA regulatory network in metastasis of PDAC has not been elucidated. The purpose of this study is to explore the role of circ_0047744/miR-21/SOCS5 in the metastasis of PDAC. We found that circRNA_0047744 was weakly expressed in PDAC tissues and cell lines. The expression of circ_0047744 was negatively correlated with lymph node metastasis and positively correlated with overall survival in PDAC patients. Functionally, the overexpression of circ_0047744 suppressed cell migration and invasion in vitro and in vivo. Mechanistically, circ_0047744 could regulate SOCS5 expression by acting as a sponge of miR-21 to inhibit migration and invasion of PDAC cells. Our study demonstrates that circ_0047744 acts as an anti-oncogene to inhibit PDAC metastasis by regulating the miR-21/SOCS5 axis, indicating that circ_0047744 may be a potential novel therapeutic target for PDAC patients.
越来越多的证据表明，环状RNA（circRNA）可作为微小RNA（miRNA）的海绵，调节包括胰腺导管腺癌（PDAC）在内的多种肿瘤的转移。然而，circRNA/miRNA调控网络在PDAC转移中的作用尚未阐明。本研究的目的是探讨circ_0047744/miR-21/SOCS5在PDAC转移中的作用。我们发现circRNA_0047744在PDAC组织和细胞系中低表达。circ_0047744的表达与PDAC患者的淋巴结转移呈负相关，与总生存期呈正相关。在功能上，circ_0047744的过表达在体外和体内均抑制细胞迁移和侵袭。机制上，circ_0047744可通过作为miR-21的海绵来调节SOCS5的表达，从而抑制PDAC细胞的迁移和侵袭。我们的研究表明，circ_0047744作为一种抑癌基因，通过调节miR-21/SOCS5轴抑制PDAC转移，表明circ_0047744可能是PDAC患者潜在的新型治疗靶点。
