Exosomes-mediated transfer of LINC00691 regulates the formation of CAFs and promotes the progression of gastric cancer
-
Published:2023-10-02
Issue:1
Volume:23
Page:
-
ISSN:1471-2407
-
Container-title:BMC Cancer
-
language:en
-
Short-container-title:BMC Cancer
Author:
Xia Bin,Gu Xiuyu,Xu Tingting,Yan Meina,Huang Lan,Jiang Chun,Li Meifen,Zhai Guanghua,Zhang Guoping,Wu Jian,Zhou Yu,Sun Chunrong,Liang Wei
Abstract
Abstract
Objective
Gastric cancer (GC) is one of the malignant tumors with the highest mortality worldwide. Our previous studies have revealed that LINC00691 is up-regulated in serum of GC patients as a novel potential biomarker for GC diagnosis and prognosis. However, the roles of serum exosomal LINC00691 in GC has not been clarified. This study aimed to find the expression pattern of serum exosomal LINC00691 in GC patients and the correlation between the level of serum exosomal LINC00691 and the pathology of gastric cancer patients.
Methods
We collected the serum of 94 GC patients before surgery and extracted exosomes to detect the expression level of exosomal LINC00691, with 21 healthy volunteers and 17 patients with benign gastric diseases as controls. Surgical GC tissues and paired healthy tissues were collected to culture primary cancer-associated fibroblasts (CAFs) and normal fibroblasts (NFs). We then treated NFs with LINC00691-rich GC cell culture supernatant or exosomes and detected the activation markers and biological functions of the fibroblasts.
Results
The results of real-time qPCR indicated that the serum exosomal LINC00691 of GC patients was significantly higher than that of healthy subjects and patients with benign gastric diseases, and was associated with the clinicopathology of GC patients. More interestingly, when the NFs were treated with GC exosomes, the level of LINC00691 was significantly increased, the cell proliferation and migration were noticeably enhanced, and the ability to accelerate GC cell proliferation and invasion was promoted, which means that the induced fibroblasts gained the properties of CAFs. In addition, we found that knockdown of LINC00691 and the use of the JAK2/STAT3 signaling pathway inhibitor ruxolitinib effectively deprived exosome-containing GC cell supernatants of the effects on NFs.
Conclusion
Our study suggested that exosomal LINC00691 promoted NFs to gained the properties of CAFs depending on JAK2/STAT3 signaling pathway as a potential diagnostic biomarker for GC.
Publisher
Springer Science and Business Media LLC
Subject
Cancer Research,Genetics,Oncology
Reference52 articles.
1. Grunberg N, Pevsner-Fischer M, Goshen-Lago T, Diment J, Stein Y, Lavon H, Mayer S, Levi-Galibov O, Friedman G, Ofir-Birin Y, et al. Cancer-associated fibroblasts promote aggressive gastric cancer phenotypes via heat shock factor 1-mediated secretion of extracellular vesicles. Cancer Res. 2021;81(7):1639–53. 2. Sun K, Lv H, Chen B, Nie C, Zhao J, Wang S, Wang J, Xu W, Chen X. Dawning precision treatment for gastric cancer: The latest biomarkers. J Transl Int Med. 2021;9(4):228–30. 3. So JBY, Kapoor R, Zhu F, Koh C, Zhou L, Zou R, Tang YC, Goo PCK, Rha SY, Chung HC, et al. Development and validation of a serum microRNA biomarker panel for detecting gastric cancer in a high-risk population. Gut. 2021, 70(5):829–837. 4. Li G, Wang G, Chi F, Jia Y, Wang X, Mu Q, et al. Higher postoperative plasma EV PD-L1 predicts poor survival in patients with gastric cancer. J Immunother Cancer. 2021;9(3):e002218. https://doi.org/10.1136/jitc-2020-002218. 5. Li P, Zhang Y, Xu Y, Cao H, Li L. Characteristics of CD8+ and CD4+ tissue-resident memory lymphocytes in the gastrointestinal tract. Advanced Gut & Microbiome Research. 2022;2022:9157455.
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
|
|