CircPIP5K1A activates KRT80 and PI3K/AKT pathway to promote gastric cancer development through sponging miR-671-5p.

Abstract

BACKGROUND:

Gastric cancer (GC) has been regarded as a kind of the most common cancers in gastrointestinal malignant tumors. Circular RNA (circRNA) is a newly discovered category of non-coding RNAs and plays a significant role in the initiation or development of human cancers. Nevertheless, the role of circPIP5K1A in GC remains unclear.

METHODS:

The relative expression level and the circular structure of circPIP5K1A were confirmedby RT-qPCR. The biological function of circPIP5K1A in GC was evaluated by colony formation, transwell and western blot assays. The binding capacity between miR-671-5p and circPIP5K1A (or KRT80) was assessed by luciferase reporter and Ago2-RIP assays. Protein levels of PI3K/AKT pathway were measured by western blot assay.

RESULTS:

CircPIP5K1A was up-regulated in GC tissues and cells with a circular structure. Functionally, circPIP5K1A silence limited cell proliferation, invasion, migration and EMT process. Mechanistically, circPIP5K1A directly interacted with miR-671-5p to modulate KRT80 expression. Either miR-671-5p inhibitor or KRT80 overexpression could offset the inhibitory effect of circPIP5K1A depletion on GC development. Besides, circPIP5K1A played its oncogenic role in GC through regulating PI3K/AKT pathway. At last, circPIP5K1A promoted GC tumor growth in vivo.

CONCLUSIONS:

CircPIP5K1A/miR-671-5p/KRT80 axis contributes to GC progression through PI3K/AKT pathway, implying this axis may be a potential therapeutic target for the treatment of GC patients.

• Authors: Hu Song, Yixin Xu, Teng Xu, Ruizhi Fan, Tao Jiang, Meng Cao, Linseng Shi, Jun Song
• Journal: Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie (Biomed Pharmacother) Vol. 126 Pg. 109941 (Jun 2020) ISSN: 1950-6007 [Electronic] France
• PMID: 32169757 (Publication Type: Journal Article)
• Copyright: Copyright © 2020. Published by Elsevier Masson SAS.

Chemical References

• KRT80 protein, human
• Keratins, Type II
• MIRN671 microRNA, human
• MicroRNAs
• RNA, Circular

Topics

• Cell Line, Tumor
• Gene Expression Regulation, Neoplastic (physiology)
• Humans
• Keratins, Type II (genetics, metabolism)
• MicroRNAs (genetics, metabolism)
• RNA, Circular (genetics, metabolism)
• Stomach Neoplasms (genetics, metabolism)
• Up-Regulation