Ma Qiang, Zhang Yijian, Liang Haibin, Zhang Fei, Liu Fatao, Chen Shili, Hu Yunping, Jiang Lin, Hao Yajuan, Li Maolan, Liu Yingbin
Department of Thyroid Oncology, Shanghai East Hospital Affiliated to Tongji University, School of Medicine, Shanghai 200120, China.
Department of General Surgery, Xinhua Hospital Affiliated with Shanghai Jiao Tong University, School of Medicine, Shanghai 200092, China; Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai 200127, China.
Cancer Lett. 2023 Oct 28;575:216398. doi: 10.1016/j.canlet.2023.216398. Epub 2023 Sep 18.
Gallbladder carcinoma (GBC) is the most common malignancy of the biliary tract, and its molecular pathogenesis remains unclear. Here we explore the functional roles of epithelial membrane protein 3 (EMP3) in GBC progression, which is aberrantly expressed in various types of cancers. The results showed that the expression level of EMP3 was reduced in human GBC tissues compared with non-malignant tissues. Further, the low expression of EMP3 was associated with the poor prognosis of GBC patients by Kaplan-Meier analysis. The ectopic expression of EMP3 inhibited GBC cell proliferation, migration and invasion in vitro and in vivo. Conversely, the depletion of EMP3 promoted GBC cell growth and metastasis. In addition, we found that EMP3 was a target gene of miR-663a, and the downregulation of EMP3 in GBC was attributed to the overexpression of miR-663a. MiR-663a was also shown to be a tumor-promoting factor mediating GBC development. In this study, we demonstrate that downregulation of EMP3 activates MAPK/ERK signaling, which regulates GBC progression. These data reveal the mechanism by which EMP3 inhibits the progression of GBC, suggesting that the miR-663a/EMP3/MAPK/ERK axis may be a new therapeutic target for GBC treatment.
胆囊癌（GBC）是胆道最常见的恶性肿瘤，其分子发病机制尚不清楚。在此，我们探讨上皮膜蛋白3（EMP3）在GBC进展中的功能作用，EMP3在多种类型癌症中异常表达。结果显示，与非恶性组织相比，人GBC组织中EMP3的表达水平降低。此外，通过Kaplan-Meier分析，EMP3的低表达与GBC患者的不良预后相关。EMP3的异位表达在体外和体内均抑制GBC细胞的增殖、迁移和侵袭。相反，EMP3的缺失促进GBC细胞生长和转移。此外，我们发现EMP3是miR-663a的靶基因，GBC中EMP3的下调归因于miR-663a的过表达。miR-663a也被证明是介导GBC发展的肿瘤促进因子。在本研究中，我们证明EMP3的下调激活MAPK/ERK信号通路，该通路调节GBC进展。这些数据揭示了EMP3抑制GBC进展的机制，表明miR-663a/EMP3/MAPK/ERK轴可能是GBC治疗的新靶点。
