Transcriptome analysis of the effect of a novel human serine protease inhibitor SPINK13 on gene expression in MHCC97-H cells.

Background: Serine peptidase inhibitor, Kazal type 13 (SPINK13) (also known as hespinter) is a low-molecular-weight inhibitor of uPA that was discovered in 2006. It was detected in prokaryotic cells in 2013 for the first time and preliminarily shown to inhibit hepG2 liver cancer cells growth in 2015. In this study, the differentially transcribed genes of MHCC97-H cells caused by SPINK13 treatment were studied by transcriptomics and the molecular mechanism of SPINK13 suppressing tumor cells was proposed using bioinformatics.

Methods: Preliminary study of the molecular mechanism of SPINK13's anti-cancer effect was performed by identifying potential target sites and signal pathways of SPINK13 through transcriptomics and bioinformatics analysis.

Results: The results of the transcriptome study showed that there were 446 significantly differentially expressed genes between the experimental group and the blank control group, of which 347 genes were up-regulated and 99 genes were down-regulated. The Gene Ontology (GO) analysis showed that differentially expressed genes were enriched in cell growth regulation and cell division. They were enriched in the signal pathways of tumor transcription and cell cycle by Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis; there were 6 classical tumor signaling pathways (P<0.001): MAPK, apoptosis, tumor necrosis factor (TNF), cell cycle, p53, and transcriptional misregulation in cancer. There were 8 genes in 2 or more classical tumor signaling pathways at the same time: , , , , , , , and . The interaction analysis of the proteins encoded by the differentially expressed genes showed that there were 35 interaction nodes in the up-regulated genes and 2 interaction nodes in the down-regulated genes.

Conclusions: This study showed that SPINK13 inhibits hepatocellular carcinoma cell development by regulating the JNK, p53, and the IKK/NF-κB pathways, its potential targets for antitumor drugs may be J, , , , , , , and .