Department of Pathology, Tianjin Medical University, Tianjin, 300070, China.
Department of Pathology, General Hospital of Tianjin Medical University, Tianjin, 300052, China.
J Gastroenterol. 2022 Oct;57(10):784-797. doi: 10.1007/s00535-022-01901-8. Epub 2022 Jul 8.
Currently, the molecular mechanism of the interaction between lncRNAs and microRNAs (miRNAs) and the target of miRNAs in tumor vasculogenic mimicry (VM) formation have not been clarified. Our aim is to study the interaction between lncRNA n339260 and miRNA30e-5p in the formation of VM.
Animal xenografts were established, 104 hepatocellular carcinoma (HCC) patients' frozen tissues were obtained and HCC cells in vitro were used to observe the role of n339260 in HCC progression.
In vivo experiment showed lncRNA n339260 promoted tumor growth and VM formation. LncRNA n339260 and miRNA30e-5p were found to be associated with VM formation, metastasis and survival time in HCC patients. In vitro experiment showed that LncRNA n339260 could inhibit miRNA30e-5p expression and TP53INP1 was found to be the downstream targets of miRNA30e-5p. Snail, MMP2, MMP9, VE-cadherin, vimentin and N-cadherin overexpression and the downregulation of TP53INP1 and E-cadherin were observed in HCCLM3 and HepG2 cells overexpressing lncRNA n339260 or in cells with decreased expression of miRNA30e-5p.
LncRNA n339260 promotes the development of VM, and lncRNA n339260 may enhance Snail expression by decreasing the expression of miRNA30e-5p, thereby reducing TP53INP1 expression. Therefore, a potential lncRNA n339260- miRNA30e-5p- TP53INP1 regulatory axis was associated with HCC progression.
目前，lncRNA 与 microRNA（miRNA）之间的相互作用及其在肿瘤血管生成拟态（VM）形成中的靶标分子机制尚不清楚。本研究旨在探讨 lncRNA n339260 与 miRNA30e-5p 在 VM 形成中的相互作用。
建立动物异种移植模型，获取 104 例肝癌（HCC）患者的冷冻组织和体外 HCC 细胞，观察 n339260 在 HCC 进展中的作用。
体内实验表明 lncRNA n339260 促进肿瘤生长和 VM 形成。lncRNA n339260 与 miRNA30e-5p 与 HCC 患者的 VM 形成、转移和生存时间相关。体外实验表明，lncRNA n339260 可抑制 miRNA30e-5p 的表达，且 TP53INP1 是 miRNA30e-5p 的下游靶基因。在过表达 lncRNA n339260 或下调 miRNA30e-5p 表达的 HCCLM3 和 HepG2 细胞中，观察到 Snail、MMP2、MMP9、VE-cadherin、vimentin 和 N-cadherin 过表达，以及 TP53INP1 和 E-cadherin 下调。
lncRNA n339260 促进 VM 的发展，lncRNA n339260 可能通过降低 miRNA30e-5p 的表达来增强 Snail 的表达，从而降低 TP53INP1 的表达。因此，lncRNA n339260-miRNA30e-5p-TP53INP1 调控轴可能与 HCC 的进展相关。
