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

• Published in: American journal of cancer research 2023-01, Vol.13 (11), p.5610-5625
• Main Authors: Wangpu, Xiongzhi, Zhao, Jingkun, Yu, Chaoran, Yu, Song, Wang, Hongcheng, Yuan, Zhou, Huang, Xinyu
• Format: Article
• Language: English
• Subjects: Original
• ISSN: 2156-6976; 2156-6976

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, , regulates PDAC progression. We used the GEO database to determine 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 , , and using qRT-PCR and investigated the effect of on cell proliferation, migration, invasion, and apoptosis 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 , , , and . Moreover, we used a naked mice model to determine how affects tumor growth and progression . Loss and gain of function analyses revealed that upregulation promotes cell proliferation, migration, invasion and tumor growth both and , which results in PDAC progression and poor prognosis in patients. knockdown significantly impaired cell proliferation and migration of PDAC cell lines. Additionally, knockdown significantly increased the expression of and , while reducing the expression of ( < 0.05), indicating that and are downstream targets of . Rescue experiments support the interactions between , , , and . In conclusion, we demonstrated that sponges the /axis, acting as an oncogene to promote PDAC development.