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Loss of keratin 23 enhances growth inhibitory effect of melatonin in gastric cancer.


ABSTRACT: To investigate the effect of keratin 23 (KRT23) on the anticancer activity of melatonin (MLT) against gastric cancer (GC) cells, microarray analysis was applied to screen differentially expressed genes in AGS GC cells following MLT treatment. Western blotting was used to detect the expression of KRT23 in GC cells and normal gastric epithelial cell line GES‑1. KRT23 knockout was achieved by CRISPR/Cas9. Assays of cell viability, colony formation, cell cycle, electric cell‑substrate impedance sensing and western blotting were conducted to reveal the biological functions of KRT23‑knockout cells without or with MLT treatment. Genes downregulated by MLT were enriched in purine metabolism, pyrimidine metabolism, genetic information processing and cell cycle pathway. Expression levels of KRT23 were downregulated by MLT treatment. Expression levels of KRT23 in AGS and SNU‑216 GC cell lines were significantly higher compared with normal gastric epithelial cell line GES‑1. KRT23 knockout led to reduced phosphorylation of ERK1/2 and p38, arrest of the cell cycle and inhibition of GC cell proliferation. Moreover, KRT23 knockout further enhanced the inhibitory activity of MLT on the tumor cell proliferation by inhibiting the phosphorylation of p38/ERK. KRT23 knockout contributes to the antitumor effects of MLT in GC via suppressing p38/ERK phosphorylation. In the future, KRT23 might be a potential prognostic biomarker and a novel molecular target for GC.

SUBMITTER: Li L 

PROVIDER: S-EPMC10784722 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature

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Loss of keratin 23 enhances growth inhibitory effect of melatonin in gastric cancer.

Li Li L   Lin Meifang M   Luo Jianhua J   Sun Huaqin H   Zhang Zhiguang Z   Lin Dacen D   Chen Lushan L   Feng Sisi S   Lin Xiuping X   Zhou Ruixiang R   Song Jun J  

Molecular medicine reports 20231215 2


To investigate the effect of keratin 23 (KRT23) on the anticancer activity of melatonin (MLT) against gastric cancer (GC) cells, microarray analysis was applied to screen differentially expressed genes in AGS GC cells following MLT treatment. Western blotting was used to detect the expression of KRT23 in GC cells and normal gastric epithelial cell line GES‑1. KRT23 knockout was achieved by CRISPR/Cas9. Assays of cell viability, colony formation, cell cycle, electric cell‑substrate impedance sens  ...[more]

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