Zhang Meixia, He Mingyan, Bai Liangliang, Du Fan, Xie Yingping, Li Bimin, Zhang Yuming
Department of Gastroenterology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China.
Department of Surgery, People's Hospital of Nanchang Economic and Technological Development Zone, Nanchang 330013, China.
Acta Biochim Biophys Sin (Shanghai). 2024 Oct 23;57(2):223-236. doi: 10.3724/abbs.2024185.
Circular RNAs play a pivotal role in the progression of various cancers. In our previous study, we observed high expression of the circRNA MALAT1 (cMALAT1) in intrahepatic cholangiocarcinoma (ICC) cells co-incubated with activated hepatic stellate cells. This study is designed to explore the roles of cMALAT1 and the underlying mechanisms in ICC. We find that cMALAT1 significantly facilitates the progression of ICC both and . The binding between cMALAT1 and miR-512-5p is subsequently confirmed through RNA pull-down experiments. As anticipated, the application of miR-512-5p mimics noticeably reverses the cMALAT1 overexpression-induced malignant phenotypes of ICC cells. Furthermore, is identified as a downstream gene of the cMALAT1/miR-512-5p axis. Importantly, silencing of not only effectively suppresses the malignant phenotypes of ICC cells but also significantly impairs the functions of cMALAT1. Our study reveals that cMALAT1 promotes the progression of ICC by competitively binding to mRNA with miR-512-5p, leading to the upregulation of VCAM1 expression and the activation of the PI3K/AKT signaling pathway.
环状RNA在多种癌症的进展中起关键作用。在我们之前的研究中,我们观察到在与活化的肝星状细胞共同孵育的肝内胆管癌(ICC)细胞中,环状RNA MALAT1(cMALAT1)高表达。本研究旨在探讨cMALAT1在ICC中的作用及其潜在机制。我们发现cMALAT1在体内和体外均显著促进ICC的进展。随后通过RNA下拉实验证实了cMALAT1与miR-512-5p之间的结合。正如预期的那样,miR-512-5p模拟物的应用显著逆转了cMALAT1过表达诱导的ICC细胞恶性表型。此外,VCAM1被鉴定为cMALAT1/miR-512-5p轴的下游基因。重要的是,沉默VCAM1不仅有效抑制ICC细胞的恶性表型,还显著损害cMALAT1的功能。我们的研究表明,cMALAT1通过与miR-512-5p竞争性结合VCAM1 mRNA促进ICC的进展,导致VCAM1表达上调和PI3K/AKT信号通路激活。