Plasma Exosomal CircNEK9 Accelerates the Progression of Gastric Cancer via miR-409-3p/MAP7 Axis

Dig Dis Sci. 2021 Jan 15. doi: 10.1007/s10620-020-06816-z. Online ahead of print.


Background: Exosome-mediated transfer of circular RNAs (circRNAs) is related to gastric cancer (GC) development. CircRNA NIMA-related kinase 9 (circNEK9; hsa_circ_0032683) was reported to be up-regulated in GC.

Aims: The biological role of circNEK9 and its underlying mechanisms in GC progression were explored.

Methods: The levels of RNAs and proteins were determined by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot assay. Cell proliferation was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay, and flow cytometry. Wound healing assay and transwell assays were conducted to analyze cell motility. Intermolecular interaction was verified by dual-luciferase reporter assay and RNA pull-down assay. Animal experiments were used to evaluate the role of circNEK9 in the growth of xenograft tumors in vivo.

Results: CircNEK9 was up-regulated in GC tissues and cell lines. CircNEK9 interference suppressed the proliferation and motility of GC cells. CircNEK9 silencing enhanced microRNA-409-3p (miR-409-3p) level through direct interaction. CircNEK9 silencing-mediated influences on the proliferation and metastasis of GC cells were partly overturned by the interference of miR-409-3p. MiR-409-3p directly interacted with microtubule-associated protein 7 (MAP7) messenger RNA (mRNA). MiR-409-3p-induced effects in GC cells were largely counteracted by the overexpression of MAP7. CircNEK9 silencing blocked GC tumor growth in vivo. Exosome-mediated transfer of circNEK9 promoted the motility of recipient GC cells.

Conclusions: CircNEK9 accelerated the proliferation, migration, and invasion of GC cells through targeting miR-409-3p/MAP7 axis. Plasma exosomal circNEK9 promoted the migration and invasion of recipient GC cells.

Keywords: CircNEK9; Exosomes; Gastric cancer; MAP7; miR-409-3p.