Page 7 - 南京医科大学自然版

第46卷第7期 南京医科大学学报（自然科学版）
2026年7月 Journal of Nanjing Medical University（Natural Sciences） ·953 ·

·专题研究：神经精神疾病·

JNK上调HOXB4基因表达对胶质瘤细胞增殖和侵袭的影响

曹丹丹 ，倪思琦 ，王迎伟 ，邱 文 ，赵晨卉 3*
1
1*
1
2
南京医科大学基础医学院免疫学系，第一临床医学院临床医学系，江苏 南京 211166；南京医科大学第一附属医院肿瘤
1 2 3
科，江苏 南京 210029

［摘 要］ 目的：观察胶质瘤组织和细胞中同源盒基因B4（homeobox gene B4，HOXB4）的表达及其对胶质瘤细胞增殖和侵袭
的影响，探究HOXB4表达的上游调控机制。方法：基于中国胶质瘤基因组图谱（Chinese Glioma Genome Atlas，CGGA）数据库，
分析胶质瘤患者肿瘤组织中HOXB4的表达水平及其与预后的相关性。通过RT⁃PCR和Western blot检测U251、U373和U87胶
质瘤细胞系中 HOXB4 的表达。通过 CCK⁃8 和 Transwell 实验评估过表达和沉默 HOXB4 对 U87 和 U251 细胞增殖和侵袭的影
响。分别用AMPK、p38 MAPK和JNK的抑制剂处理U87细胞，再用RT⁃PCR和Western blot 检测HOXB4的表达水平，CCK⁃8和
Transwell检测细胞的增殖和侵袭程度。在U87细胞中过表达HOXB4，并给予JNK抑制剂，开展RT⁃PCR、Western blot、CCK⁃8和
Transwell实验，检测HOXB4表达、细胞增殖及侵袭水平。结果：胶质瘤患者的肿瘤组织中HOXB4高表达，且与肿瘤的恶性程
度以及患者不良预后相关。U251、U373和U87细胞系均表达HOXB4，其中以U87细胞表达量最高。过表达HOXB4显著增强
U87 和 U251 细胞的增殖和侵袭，沉默 HOXB4 则明显抑制上述表型。JNK 抑制剂可显著下调 U87 细胞中 HOXB4 的表达，而
AMPK抑制剂和p38 MAPK抑制剂则无明显作用。JNK抑制剂可减弱U87细胞的增殖和侵袭，而HOXB4过表达可拮抗JNK抑
制剂的上述作用。结论：胶质瘤细胞中JNK激活可上调HOXB4的表达，从而促进细胞的增殖和侵袭。
［关键词］ 胶质瘤；HOXB4；JNK；增殖；侵袭
［中图分类号］ R739.41 ［文献标志码］ A ［文章编号］ 1007⁃4368（2026）07⁃953⁃10
doi：10.7655/NYDXBNSN260081

The effect of JNK⁃induced upregulation of HOXB4 gene expression on the proliferation
and invasion of glioma cells
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CAO Dandan ，NI Siqi ，WANG Yingwei ，QIU Wen ，ZHAO Chenhui 3*
1 Department of Immunology，School of Basic Medicine，Clinical Medical Science of the First Clinical Medical
2
College，Nanjing Medical University，Nanjing 211166；Department of Oncology，the First Affiliated Hospital of
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Nanjing Medical University，Nanjing 210029，China
［Abstract］ Objective：To investigate the expression of homeobox gene B4（HOXB4）in glioma tissues and cells，as well as its effects
on glioma cell proliferation and invasion，and to explore the upstream regulatory mechanisms of HOXB4 expression. Methods：Based
on the Chinese Glioma Genome Atlas（CGGA）database，the expression level of HOXB4 in glioma tissues and its correlation with
patient prognosis were analyzed. RT⁃PCR and Western blot were used to detect HOXB4 expression in U251，U373，and U87 glioma
cell lines. The effects of HOXB4 overexpression and silencing on the proliferation and invasion of U87 and U251 cells were assessed
using CCK⁃8 and Transwell assays. U87 cells were treated with inhibitors of AMPK，p38 MAPK，and JNK. The expression of HOXB4
was detected by RT⁃PCR and Western blot. The cell proliferation and invasion levels were examined by CCK⁃8 and Transwell assays.
HOXB4 was overexpressed in U87 cells in the presence of a JNK inhibitor，and the HOXB4 expression，cell proliferation and invasion
were determined by RT⁃PCR，Western blot，CCK⁃8，and Transwell assays. Results：HOXB4 was highly expressed in glioma tissues and
was associated with tumor malignancy and poor patient prognosis. HOXB4 was expressed in U251，U373，and U87 cell lines，with the
highest expression in U87 cells. Overexpression of HOXB4 obviously enhanced the proliferation and invasion of U87 and U251 cells，

［基金项目］ 国家自然科学基金（81902878）；江苏省大学生创新训练计划（202010312039Y）
∗
通信作者（Corresponding author），E⁃mail：qiuwen@njmu.edu.cn（ORCID：0000⁃0003⁃2097⁃9773）；chenhuizhao@njmu.edu.cn（OR⁃
CID：0000⁃0002⁃7950⁃5225）