Depletion of LINC01133 from cancer-associated fibroblasts exacerbates the progression of gastric adenocarcinoma
During tumorigenesis, fibroblasts transition from homeostatic cells to cancer-promoting entities, a process potentially mediated by long non-coding RNAs (lncRNAs). While some oncogenic lncRNAs facilitate carcinogenesis, the role of downregulated homeostatic lncRNAs remains unclear. This study reveals that LINC01133, primarily expressed in fibroblasts, is significantly reduced in cancer-associated fibroblasts. The decreased expression of LINC01133 in gastric adenocarcinoma-associated fibroblasts diminishes its extracellular-vesicle-mediated uptake by tumor cells, leading to the acceleration of gastric cancer progression. KLF4 regulates the transcription of LINC01133 in fibroblasts. Mechanistically, binding of LINC01133 to the 173-191 residue region of CDC42 suppresses the activity of its downstream kinases PAK3 and MLK3, and LINC01133 was also the sponge of miR-199a-5p, thereby competing with PHLPP1. <i>In vivo</i> studies confirmed that either overexpression of LINC01133 or inhibition of miR-199a-5p suppresses gastric adenocarcinoma cell growth. In summary, LINC01133 re-activation may serve as a potential therapeutic strategy for inhibiting metastasis in gastric adenocarcinoma.
Authors
- Tianyi Fang (ORCID: https://orcid.org/0000-0002-5015-4898)
- Mengdi Cai (ORCID: https://orcid.org/0000-0003-4547-136X)
- Songbin Fu (ORCID: https://orcid.org/0000-0003-0382-9888)
- Gui Fu (ORCID: https://orcid.org/0000-0001-8461-3717)
- Jiaqi Li (ORCID: https://orcid.org/0000-0001-8422-0390)
- Xiao Liang (ORCID: https://orcid.org/0000-0003-0921-0023)
- Shengnan Jiang (ORCID: https://orcid.org/0000-0002-8111-7571)
- Jingcui Yu (ORCID: https://orcid.org/0000-0002-1936-4379)
- Jie Wu (ORCID: https://orcid.org/0000-0001-8141-9417)
- Linlin Li (ORCID: https://orcid.org/0000-0002-8751-9491)
- Yimin Wang (ORCID: https://orcid.org/0000-0003-2515-6602)
- Qian Zhang (ORCID: https://orcid.org/0000-0003-4928-3366)
- He Zhang (ORCID: https://orcid.org/0000-0002-3283-8620)
- Liqiang Wang (ORCID: https://orcid.org/0000-0002-1265-4656)
- Xue Guan
- Mengya Li (ORCID: https://orcid.org/0000-0002-9581-4044)
- Yingwei Xue
- Yu‐Ting Weng (ORCID: https://orcid.org/0000-0003-2713-7579)
- Wenjing Sun (ORCID: https://orcid.org/0000-0003-3924-1832)
- Yunlong Li (ORCID: https://orcid.org/0000-0002-4253-3206)
- Kexian Dong
- Weixin Qin
- Shuaihang Pang
- Xiangning Meng
Institutions
- Ministry of Education of the People's Republic of China (CN)
- Harbin Medical University (CN)
- Third Affiliated Hospital of Harbin Medical University (CN)
- Second Affiliated Hospital of Harbin Medical University (CN)
Publication Details
- Journal
- iScience
- Published
- 2025-10-29
- DOI
- https://doi.org/10.1016/j.isci.2025.113886
- Primary Topic
- Cancer-related molecular mechanisms research
- Type
- article
- Field-Weighted Citation Impact
- 0.00