CircPTPRA promotes the progression of pancreatic ductal adenocarcinoma via the miR-140-5p/LMNB1 axis

Author:

Fu Wen1,Wang Xianxing2,Xiang Jifeng2,Chen Shengkai2,Xia Renpei2,Qin Fanbo1,Li Zhuo3,Wang Huaizhi2,Xie Chuanming4,Liu Changjiang5

Affiliation:

1. Chongqing Medical University

2. Chongqing general Hospital

3. Chinese Academy of Sciences

4. Southwest Hospital

5. Chongqing Population and Family Planning Science and Technology Research Institute

Abstract

Abstract Background Growing evidence suggests that circular RNAs (circRNAs) are important factors in cancer progression. Nevertheless, the role of circRNAs in the progression of pancreatic ductal adenocarcinoma (PDAC) remains unclear. Methods CircPTPRA was identified based on our previous circRNA array data analysis. Wound healing, transwell and EdU assays were performed to investigate the effect of circPTPRA on the migration, invasion and proliferation of PDAC cells in vitro. RNA pull-down, fluorescence in situ hybridization (FISH), RNA immunoprecipitation (RIP), and dual-luciferase reporter assays were conducted to verify the binding of circPTPRA with miR-140-5p. Subcutaneous xenograft models were constructed for in vivo experiments. Results CircPTPRA was significantly upregulated in PDAC tissues and cells compared to normal controls. Moreover, circPTPRA overexpression was positively correlated with lymph node invasion and worse prognosis in PDAC patients. In addition, overexpression of circPTPRA promoted PDAC migration, invasion, proliferation and epithelial-mesenchymal transition (EMT) in vitro and in vivo. Mechanistically, circPTPRA upregulates LaminB1 (LMNB1) expression by sponging miR-140-5p and ultimately promots the progression of PDAC. Conclusions This study revealed that circPTPRA plays an important role in the progression of PDAC by sponging miR-140-5p. It can be explored as a potential prognostic marker and therapeutic target for PDAC.

Publisher

Research Square Platform LLC

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