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Profiling and Characterization of microRNAs Responding to Sodium Butyrate Treatment in Gastric Cancer Cells

Author(s):

Gongping Sun, He Duan, Jin Meng and Dewei Zhang*  

Abstract:


Background: Short-chain fatty acids exert anti-cancer effects on tumor cells.

Objective: We aimed to reveal the signaling network altered by butyrate in Gastric Cancer (GC) using small RNA sequencing (sRNA-seq).

Methods: The effects of butyrate on the biological behavior of NCI-N87 and KATO III cells in vitro were assessed by functional assays and half-maximal inhibitory concentrations (IC50) of butyrate in KATO III cells were calculated. sRNA-seq was performed on KATO III cells. Differentially expressed miRNAs (DE-miRNAs) were identified between butyrate treatment and control groups using DESeq2, and miRNA targets were predicted. A protein-protein interaction (PPI) network of DE-miRNA targets was created using Metascape. Key MCODE complexes were identified using the MCODE algorithm and cluster Profiler. The relationship between DE-miRNA and GC overall survival (OS) was evaluated using Kaplan-Meier curves.

Results: Butyrate dose-dependently inhibited NCI-N87 and KATO III cell viability. KATO III cells were more sensitive to butyrate than NCI-N87 cells. Butyrate promoted apoptosis and inhibited KATO III cell migration. Total 324 DE-miRNAs were identified in KATO III cells, and 459 mRNAs were predicted as targets of 83 DE-miRNAs. Two key protein complexes were identified in a PPI network of the 459 targets. A key signaling network responding to butyrate were generated using targets in these key complexes and their miRNA regulators. The DE-miRNAs in the key signaling network were related to the OS of GC.

Conclusion: Butyrate altered the biological behavior of GC cells, which may be achieved by regulating miRNAs and related oncogenic pathways.

Keywords:

Gastric cancer, microRNA, small RNA, sequencing, oncogenic signaling, sodium butyrate treatment

Affiliation:

Department of General Surgery, The Fourth Affiliated Hospital of the China Medical University, Shenyang 110032, Liaoning, Department of General Surgery, The Fourth Affiliated Hospital of the China Medical University, Shenyang 110032, Liaoning, Shenyang Anorectal Hospital, Shenyang 110000, Liaoning, Department of General Surgery, The Fourth Affiliated Hospital of the China Medical University, Shenyang 110032, Liaoning



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