CircATP13A1(hsa_circ_0000919) promotes cell proliferation and metastasis and inhibits cell apoptosis in pancreatic ductal adenocarcinoma via the miR-186/miR-326/HMGA2 axis: implications for novel therapeutic targets

Pancreatic ductal adenocarcinoma (PDAC) is a notoriously aggressive malignancy with a survival rate of merely 9%. The prognosis in patients with PDAC is relatively poor, particularly in patients with advanced distant metastases. However, the mechanisms of PDAC progression remain elusive. Circular RNAs (circRNAs) have been implicated in the development of various malignancies, including PDAC. Therefore, this study aimed to investigate how a novel circRNA, circATP13A1, regulates PDAC progression. We used the GEO database to determine circATP13A1 expression levels in cancer and adjacent cells and employed the limma package of R software to identify differentially expressed circRNAs. We detected the expression of circATP13A1, miR-186, and miR-326 using qRT-PCR and investigated the effect of circATP13A1 on cell proliferation, migration, invasion, and apoptosis in vitro using the Cell Counting Kit-8 (CCK-8), the transwell migration assay, and the flow cytometry assay. We then performed RNA pull-down assay, RNA immunoprecipitation (RIP), and Western blot to verify the interaction between circATP13A1, miR-186, miR-326, and HMGA2. Moreover, we used a naked mice model to determine how circATP13A1 affects tumor growth and progression in vivo. Loss and gain of function analyses revealed that circATP13A1 upregulation promotes cell proliferation, migration, invasion and tumor growth both in vitro and in vivo, which results in PDAC progression and poor prognosis in patients. CircATP13A1 knockdown significantly impaired cell proliferation and migration of PDAC cell lines. Additionally, circATP13A1 knockdown significantly increased the expression of miR186 and miR-326, while reducing the expression of HMGA2 (P < 0.05), indicating that miR-186 and miR-326 are downstream targets of circATP13A1. Rescue experiments support the interactions between circATP13A1, miR-186, miR-326, and HMGA2. In conclusion, we demonstrated that circATP13A1 sponges the miR-186/miR-326/HMGA2/ axis, acting as an oncogene to promote PDAC development.