期刊
BIOLOGICAL CHEMISTRY
卷 403, 期 10, 页码 945-958出版社
WALTER DE GRUYTER GMBH
DOI: 10.1515/hsz-2022-0153
关键词
apoptosis; ARHGEF9; gastric cancer; lncRNA-p21; miR-514b-3p
资金
- International Cooperative Project of Shaanxi Province, People's Republic of China [2019KW-077, 2022KW-01]
The tumor suppressor gene lncRNA-p21 was found to be associated with advanced disease stage and poor survival in gastric cancer. Through regulating the expression of miR-514-3p and ARHGEF9, lncRNA-p21 influenced the proliferation and apoptosis of gastric cancer cells. This study reveals a novel lncRNA-p21/miR-514b-3p/ARHGEF9 pathway that can be targeted for gastric cancer therapy.
The long non-coding RNA p21 (lncRNA-p21) was a tumor suppressor gene in most cancer types including gastric cancer (GC). We aimed to identify a specific lncRNA-p21-involved pathway in regulating the proliferation and apoptosis of GC cells. A lower lncRNA-p21 expression in tumors was associated with advanced disease stage and predicted worse survival of GC patients. LncRNA-p21 overexpression in GC cell line somatic gastric cancer (SGC)-7901 and human gastric cancer (HGC)-27 suppressed cell proliferation and enhanced apoptosis, while lncRNA-p21 knockdown caused the opposite effects. Through bioinformatics analysis and luciferase-based reporter assays, we identified miR-514b-3p as a sponge target of lncRNA-p21. Cdc42 guanine nucleotide exchange factor 9 (ARHGEF9), functioned as a tumor suppress factor in GC, was found as the downstream target of miR-514-3p, and their expressions were negatively correlated in GC tumor tissues. In addition, like lncRNA-p21 overexpression alone, miR-514-3p inactivation alone also led to decreased proliferation and increased apoptosis in SGC-7901 and HGC-27 cells, which were markedly attenuated by additional ARHGEF9 knockdown. Xenograft SGC-7901 cells with more lncRNA-p21 or ARHGEF9 expressions or with less miR-514-3p expression exhibited obviously slower in vivo growth than the control SGC-7901 cells in nude mice. Our study reveals a novel lncRNA-p21/miR-514b-3p/ARHGEF9 pathway that can be targeted for GC therapy.
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