胰腺导管腺癌(PDAC)是一种众所周知的侵袭性恶性肿瘤,生存率仅为9%。PDAC患者的预后相对较差,特别是晚期远处转移患者。然而,PDAC进展的机制仍然难以捉摸。环状RNA(circularRNAs)与各种恶性肿瘤的发展有关,包括PDAC。因此,这项研究旨在探讨一种新型的circRNA,cirATP13A1,调节PDAC进展。我们使用GEO数据库来确定circATP13A1在癌症和邻近细胞中的表达水平,并使用R软件的limma包来鉴定差异表达的circRNAs。我们使用qRT-PCR检测了circATP13A1,miR-186和miR-326的表达,并研究了ciratP13A1对细胞增殖的影响。迁移,入侵,使用细胞计数试剂盒-8(CCK-8)进行体外凋亡,Transwell迁移试验,和流式细胞术测定。然后我们进行了RNA下拉法,RNA免疫沉淀(RIP),和Westernblot验证circATP13A1、miR-186、miR-326和HMGA2之间的相互作用。此外,我们使用裸鼠模型来确定circatP13A1如何影响体内肿瘤的生长和进展.功能的损失和获得分析显示,circatp13A1上调促进细胞增殖,迁移,在体外和体内的侵袭和肿瘤生长,导致PDAC进展和患者预后不良。CircATP13A1敲低显著损害PDAC细胞系的细胞增殖和迁移。此外,ciratP13A1基因敲除显著增加miR-186和miR-326的表达,同时降低HMGA2的表达(P<0.05),表明miR-186和miR-326是circatP13A1的下游靶标。挽救实验支持circATP13A1、miR-186、miR-326和HMGA2之间的相互作用。总之,我们证明,circATP13A1海绵miR-186/miR-326/HMGA2/轴,作为促进PDAC发育的致癌基因。
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 miR-186 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.