Department of Gastroenterology, Qingyuan People's Hospital, the Sixth Affiliated Hospital of Guangzhou Medical University; Institute of Digestive Disease of Guangzhou Medical University, Guangzhou, 511518, Guangdong, China.
Department of Anesthesiology, Guizhou Provincial People's Hospital, Guiyang, 550003, Guizhou, China.
Cell Biochem Biophys. 2021 Mar;79(1):123-131. doi: 10.1007/s12013-020-00948-9. Epub 2020 Oct 3.
This study aims to explore the role of Gastrokin-2 (GKN2) in gastric cancer and its function in the progression and metastasis of gastric cancer. The expression of GKN2 in the patient samples was examined by qRT-PCR and western blot. The transcription factor NK6 Homeobox 2 (NKX6-2), which binds to the GKN2 promoter, was predicted by cBioportal and JSPAR. Binding between NKX6-2 and the GKN2 promoter was analyzed by dual-luciferase assay. MTT assay and transwell assay were used to detect changes in gastric cancer cell viability and migration after GKN2 overexpression, which was achieved by transfection of GKN2 overexpression vector. Akt signaling pathway markers were assessed by western blot. GKN2 is downregulated in gastric cancer and low GKN2 expression is correlated to poor survival, metastasis, and higher clinical stages. NKX6-2 binds the promoter region of GKN2 and regulate its expression. GKN2 overexpression inhibits the proliferation, migration, and invasion of gastric cancer cells, which was mediated by Akt signaling pathway. NKX6-2 regulated GKN2 inhibits the proliferation and invasion of gastric cancer cells by inhibiting Akt signaling pathway. GKN2 can be used as a potential diagnostic and therapeutic target for patients with clinical gastric cancer.
本研究旨在探讨胃泌素释放肽前体（Gastrin-Releasing Peptide Precursor，GRP）在胃癌中的作用及其在胃癌进展和转移中的功能。通过 qRT-PCR 和 Western blot 检测患者样本中 GKN2 的表达。通过 cBioportal 和 JSPAR 预测与 GKN2 启动子结合的转录因子 NK6 同源盒 2（NKX6-2）。通过双荧光素酶报告基因实验分析 NKX6-2 与 GKN2 启动子的结合。通过转染 GKN2 过表达载体检测 GKN2 过表达后胃癌细胞活力和迁移的变化，采用 MTT assay 和 transwell assay。通过 Western blot 检测 Akt 信号通路标志物。GKN2 在胃癌中下调，低表达与生存率差、转移和较高的临床分期相关。NKX6-2 结合 GKN2 启动子区域并调节其表达。GKN2 过表达通过 Akt 信号通路抑制胃癌细胞的增殖、迁移和侵袭。NKX6-2 调节 GKN2 通过抑制 Akt 信号通路抑制胃癌细胞的增殖和侵袭。GKN2 可作为临床胃癌患者潜在的诊断和治疗靶点。
