Fusobacterium nucleatum-induced exosomal HOTTIP promotes gastric cancer progression through the microRNA-885-3p/EphB2 axis.

Abstract

Recent studies have reported that Fusobacterium nucleatum (Fn) is associated with gastric cancer (GC). Cancer-derived exosomes contain key regulatory noncoding RNAs and are a crucial medium of intercellular communication. However, the function and regulatory mechanism of exosomes (Fn-GCEx) secreted from Fn-infected GC cells remains unclear. In this study, Fn-GCEx enhanced the proliferation, migration, and invasion capacity of GC cells in vitro, as well as tumor growth and metastasis in vivo. HOTTIP was also upregulated in GC cells treated with Fn-GCEx. Moreover, knockdown of HOTTIP weakened the effects of Fn-GCEx in recipient GC cells. Mechanistically, HOTTIP promoted EphB2 expression by sponging microRNA (miR)-885-3p, thus activating the PI3K/AKT pathway in Fn-GCEx treated GC cells. Overall, Fn infection induced the upregulation of exosomal HOTTIP from GC cells that subsequently promoted GC progression through the miR-885-3p/EphB2/PI3K/AKT axis. Herein, we identify a potential molecular pathway and therapeutic target for GC.

• Authors: Yiwei Xin, Xinyang Li, Mengjiao Zhang, Ziqi Shang, Zhengdong Luo, Yifeng Wang, Xinru Gui, Qi Liu, Tingting Li, Shunjie Zeng, Helgi B Schiöth, Xin Zhang, Yi Zhang
• Journal: Cancer science (Cancer Sci) Vol. 114 Issue 6 Pg. 2360-2374 (Jun 2023) ISSN: 1349-7006 [Electronic] England
• PMID: 36898846 (Publication Type: Journal Article)
• Copyright: © 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Chemical References

• MicroRNAs
• Proto-Oncogene Proteins c-akt
• Phosphatidylinositol 3-Kinases
• RNA, Long Noncoding
• MIRN885 microRNA, human

Topics

• Humans
• Stomach Neoplasms (pathology)
• MicroRNAs (genetics, metabolism)
• Fusobacterium nucleatum (genetics)
• Proto-Oncogene Proteins c-akt (metabolism)
• Phosphatidylinositol 3-Kinases (metabolism)
• Gene Expression Regulation, Neoplastic
• Cell Line, Tumor
• Cell Proliferation (genetics)
• RNA, Long Noncoding (genetics, metabolism)