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28 July 2020 : Laboratory Research  

CircKIAA0907 Retards Cell Growth, Cell Cycle, and Autophagy of Gastric Cancer In Vitro and Inhibits Tumorigenesis In Vivo via the miR-452-5p/KAT6B Axis

Lingyu Zhu1BCDE, Chunfei Wang1CDEF, Shengquan Lin2BCDE, Lei Zong1ABCD*

DOI: 10.12659/MSM.924160

Med Sci Monit 2020; 26:e924160

Abstract

BACKGROUND: The significant roles of circular ribonucleic acids (RNAs) in cancers have been discussed in many studies. This report aimed to investigate the biological functions of circKIAA0907 and its action mechanism in gastric cancer (GC).

MATERIAL AND METHODS: Relative RNA expression levels were determined using quantitative real-time polymerase chain reaction (qRT-PCR). The examination of cell proliferation was performed via 3-(4, 5-dimethylthiazol-2-y1)-2, 5-diphenyl tetrazolium bromide assay. Flow cytometry was used to analyze the apoptosis rate and cell cycle. Protein levels were quantified using western blot. Biotinylated RNA pull-down assay was used to find the microRNA target of circKIAA0907; target binding was validated through dual-luciferase reporter assay. The assay in vivo was executed via a xenograft tumor model to explore the role of circKIAA0907 in GC.

RESULTS: CircKIAA0907 was downregulated in GC and had higher stability than its linear isoform. Functionally, circKIAA0907 upregulation resulted in the repression of proliferation, cell cycle, and autophagy and promotion of apoptosis in GC cells. Mechanistically, circKIAA0907 bound to miR-452-5p as a specific sponge for it; lysine acetyltransferase 6B (KAT6B) was a target gene of miR-452-5p, so circKIAA0907 elevated KAT6B levels via sponging miR-452-5p. Reversion assays indicated that circKIAA0907 served as a tumor inhibitor by inhibiting miR-452-5p and increasing KAT6B; miR-452-5p inhibition impeded GC development by upregulating KAT6B. The miR-452-5p/KAT6B axis was also accountable for circKIAA0907-induced tumorigenesis suppression in vivo.

CONCLUSIONS: This work demonstrated that circKIAA0907 has diagnostic and therapeutic value in GC by acting as an oncogenic molecule via the miR-452-5p/KAT6B axis.

Keywords: Stomach Neoplasms

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Medical Science Monitor eISSN: 1643-3750
Medical Science Monitor eISSN: 1643-3750