酸性微环境通过长链非编码RNA-LOC100507424/E2F1/FOXM1轴促进胰腺癌进展。

The acidic microenvironment promotes pancreatic cancer progression via the lncRNA-LOC100507424/E2F1/FOXM1 axis.

作者信息

Mu Deyang, Shi Ying, Sun Runxuan, Han Bing, Zhong Kai, Ye Yilu, Zhang Jungang

机构信息

Department of Pharmacology, School of Basic Medical Sciences and Forensic Medicine, Hangzhou Medical College, Hangzhou, 311300, Zhejiang, P.R. China.

General Surgery, Hepatobiliary and Pancreatic Surgery and Minimally Invasive Surgery, Oncology Center, Zhejiang Provincial People's Hospital, People's Hospital of Hangzhou Medical College, Hangzhou, China.

出版信息

BMC Cancer. 2025 Apr 10;25(1):655. doi: 10.1186/s12885-025-14073-4.

DOI:10.1186/s12885-025-14073-4

PMID:40211195

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11984246/

Abstract

Pancreatic cancer is highly aggressive and sensitive to acidic microenvironments, which promote cancer cell survival and invasion. Long non-coding RNAs (lncRNAs) play crucial roles in cancer biology, helping cells adapt to microenvironmental changes, but their functions in the acidic microenvironment of pancreatic cancer are understudied. This study investigated the role of lncRNA LOC100507424 in pancreatic cancer, previously linked to glioma stem cells. Clinical specimens and cell line models cultured under acidic conditions showed that LOC100507424 was upregulated in pancreatic cancer tissues and further increased in acidic environments. Functional assays demonstrated that knockdown of LOC100507424 inhibited cell proliferation, invasion and metastasis. Mechanistically, LOC100507424 transcriptionally regulated FOXM1 expression through its interaction with E2F1. In vivo studies confirmed that LOC100507424 promoted tumor growth in nude mice. These findings highlight the significance of lncRNAs in the acidic microenvironment of pancreatic cancer and suggest potential therapeutic targets.

摘要

胰腺癌具有高度侵袭性，且对促进癌细胞存活和侵袭的酸性微环境敏感。长链非编码RNA（lncRNAs）在癌症生物学中发挥着关键作用，帮助细胞适应微环境变化，但其在胰腺癌酸性微环境中的功能尚未得到充分研究。本研究调查了lncRNA LOC100507424在胰腺癌中的作用，该lncRNA此前与胶质瘤干细胞有关。在酸性条件下培养的临床标本和细胞系模型显示，LOC100507424在胰腺癌组织中上调，在酸性环境中进一步增加。功能试验表明，敲低LOC100507424可抑制细胞增殖、侵袭和转移。机制上，LOC100507424通过与E2F1相互作用转录调控FOXM1表达。体内研究证实，LOC100507424促进裸鼠肿瘤生长。这些发现突出了lncRNAs在胰腺癌酸性微环境中的重要性，并提示了潜在的治疗靶点。