LINC01133 通过与 Arp3 结合促进 SPP1 介导的胰腺导管腺癌上皮-间充质转化。

LINC01133 promotes pancreatic ductal adenocarcinoma epithelial-mesenchymal transition mediated by SPP1 through binding to Arp3.

机构信息

Department of Pathology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, Jiangsu, 210029, China.

出版信息

Cell Death Dis. 2024 Jul 10;15(7):492. doi: 10.1038/s41419-024-06876-3.

DOI:10.1038/s41419-024-06876-3

PMID:38987572

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11237081/

Abstract

Pancreatic ductal adenocarcinoma (PDAC) is a lethal disease with limited treatment methods. Long non-coding RNAs (lncRNAs) have been found involved in tumorigenic and progression. The present study revealed that LINC01133, a fewly reported lncRNA, was one of 16 hub genes that could predict PDAC patients' prognosis. LINC01133 was over-expressed in PDAC tumors compared to adjacent pancreas and could promote PDAC proliferation and metastasis in vitro and in vivo, as well as inhibit PDAC apoptosis. LINC01133 expression positively correlated to secreted phosphoprotein 1 (SPP1) expression, leading to an enhanced epithelial-mesenchymal transition (EMT) process. LINC01133 bound with actin-related protein 3 (Arp3), the complex reduced SPP1 mRNA degradation which increased SPP1 mRNA level, ultimately leading to PDAC proliferation. This research revealed a novel mechanism of PDAC development and provided a potential prognosis indicator that may benefit PDAC patients.

摘要

胰腺导管腺癌（PDAC）是一种致命的疾病，治疗方法有限。长链非编码 RNA（lncRNA）已被发现参与肿瘤发生和进展。本研究表明，LINC01133 是一种报道较少的 lncRNA，是 16 个可预测 PDAC 患者预后的关键基因之一。与相邻胰腺相比，LINC01133 在 PDAC 肿瘤中表达上调，可促进 PDAC 的体外和体内增殖和转移，并抑制 PDAC 细胞凋亡。LINC01133 的表达与分泌型磷蛋白 1（SPP1）的表达呈正相关，导致上皮间质转化（EMT）过程增强。LINC01133 与肌动蛋白相关蛋白 3（Arp3）结合，复合物减少 SPP1 mRNA 的降解，增加 SPP1 mRNA 水平，最终导致 PDAC 增殖。这项研究揭示了 PDAC 发展的新机制，并提供了一个潜在的预后指标，可能使 PDAC 患者受益。