He Lei, Qian Xiaohan, Ge Pingping, Fan Dong, Ma Xiang, Wu Qiong, Sun Jin, Yang Lihua, Shen Jian, Xu Lijian
Department of General Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Medical Center for Digestive Disease, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Front Oncol. 2022 Apr 12;12:708081. doi: 10.3389/fonc.2022.708081. eCollection 2022.
Gastric cancer (GC) is a prevalent cancer with high mortality and strong invasiveness, and the entire regulatory networks of GC is still unclear.
The aim of this study was to explore the specific mechanism of the effect of nucleolar protein 6 (NOL6) on the proliferation and apoptosis of GC cells.
The human gastric adenocarcinoma cell line HGC-27 and AGS were cultured. qRT-PCR was used to verify the expression level of NOL6 in GC cells; MTT and EdU were used to test cell proliferation; TUNEL staining and Flow cytometry were used to detect cell apoptosis; The downstream genes and pathways following NOL6 knockdown were explored through the microarray assay and ingenuity pathway analysis, and the downstream genes were finally verified by qRT-PCR and Western blotting. The xenograft mice were used to investigate the effect of NOL6 on GC .
TCGA data analysis showed that NOL6 expression level was higher in GC cells than adjacent normal cells. Over-expression of NOL6 increased proliferation and colony formation, and inhibited the apoptotic rate in AGS and HGC-27 cells, while NOL6 knockdown induced the opposite effects. Through microarray assay and IPA analysis, NOL6-related downstream genes and critical signaling pathways were found. And we verified the relationship between downstream genes and GC. Additionally, NOL6 knockdown could decrease the weight and volume of tumor in the mice.
NOL6 knockdown could inhibit cell proliferation and induce cell apoptosis of GC, suggesting that NOL6 may serve as a potential therapeutic target for treating GC.
胃癌（GC）是一种常见的癌症，具有高死亡率和强侵袭性，其完整的调控网络仍不明确。
本研究旨在探讨核仁蛋白6（NOL6）对GC细胞增殖和凋亡影响的具体机制。
培养人胃腺癌细胞系HGC-27和AGS。采用qRT-PCR验证GC细胞中NOL6的表达水平；采用MTT和EdU检测细胞增殖；采用TUNEL染色和流式细胞术检测细胞凋亡；通过基因芯片分析和 Ingenuity 通路分析探索NOL6敲低后的下游基因和通路，最终通过qRT-PCR和蛋白质印迹法验证下游基因。利用异种移植小鼠研究NOL6对GC的影响。
TCGA数据分析显示，GC细胞中NOL6表达水平高于相邻正常细胞。NOL6过表达增加了AGS和HGC-27细胞的增殖和集落形成，并抑制了凋亡率，而NOL6敲低则产生相反的效果。通过基因芯片分析和IPA分析，发现了与NOL6相关的下游基因和关键信号通路。并且我们验证了下游基因与GC之间的关系。此外，NOL6敲低可降低小鼠肿瘤的重量和体积。
NOL6敲低可抑制GC细胞增殖并诱导其凋亡，提示NOL6可能作为治疗GC的潜在治疗靶点。
