Nanog promotes proliferation, migration, and invasion of gastric cancer cells via regulation of the KDM5B/H3K4me3 epigenetic axis.
TL;DR
The Nanog/KDM5B/H3K4me3 pathway contributes to the proliferation, migration, and invasion of SGC-7901 cells by inhibiting E-cadherin and enhancing N-cadherin.
Abstract
Background
Nanog, a transcription factor, is involved in cancer initiation and progression.
Objectives
To explore the potential regulatory mechanism of Nanog in gastric cancer. MATERIAL AND
Methods
Immunohistochemistry (IHC) was used to examine E-cadherin, N-cadherin, Nanog, and KDM5B in gastric cancer (Ca), metastatic lymph node cancer (L), and adjacent normal tissues (N). MTT, migration, and invasion assays were used to evaluate cell viability, migration, and invasion of gastric cancer cells SGC-7901 induced by transforming growth factor (TGF)-β1, or with Nanog overexpression/knockdown. Western blot was used to examine the relative protein expression of E-cadherin, N-cadherin, Nanog, and lysine-specific demethylase 5B (KDM5B) in cells. KDM5B was silenced by siRNA in cells, and E-cadherin, N-cadherin, and H3K4me3 were examined with western blot, while the interaction between Nanog and KDM5B was examined using a co-immunoprecipitation (Co-IP) assay. Furthermore, H3K4me3 protein expression was validated in N, Ca, and L tissues using IHC.
Results
E-cadherin was hypoexpressed, while N-cadherin, Nanog, and KDM5B were hyperexpressed in the Ca and L groups compared with the N group. TGF-β1 and Nanog enhanced cell viability, migration, and invasion by promoting epithelial-mesenchymal transition (EMT). KDM5B was identified to bind to Nanog and was positively regulated by Nanog, and functioned as a negative regulator of histone H3 Lys4 trimethylation (H3K4me3) in SGC-7901 cells. KDM5B knockdown inhibited cell invasion and EMT. The Nanog/KDM5B/H3K4me3 pathway contributes to the proliferation, migration, and invasion of SGC-7901 cells by inhibiting E-cadherin and enhancing N-cadherin.
Conclusions
This study provides new insights into the regulatory role and mechanism of Nanog/KDM5B/H3K4me3 in gastric cancer, which might be potential biomarkers in the diagnosis and prognosis of gastric cancer.