Department of Pathogenobiology, The Key Laboratory of Zoonosis, Chinese Ministry of Education, College of Basic Medicine, Jilin University, Changchun, China.
Cardiovascular Disease Center, The First Hospital of Jilin University, Jilin University, Changchun, China.
Int J Biol Macromol. 2024 Sep;276(Pt 2):134011. doi: 10.1016/j.ijbiomac.2024.134011. Epub 2024 Jul 18.
Gastric cancer (GC) is one of the most common malignant tumors in the world, ranking fourth in incidence and second in mortality among malignant tumors. In recent years, there has been some progress in biological treatment and targeted treatment for gastric cancer, but the prognosis for gastric cancer patients remains pessimistic, and the molecular mechanisms involved are not yet clear. In this study, bioinformatics analysis showed that Ubiquitin-conjugating enzyme E2C(UBE2C) was abnormally expressed in various types of cancer. Furthermore, UBE2C protein and mRNA expression was significantly elevated in gastric cancer tissues and cells. Silencing UBE2C significantly inhibited the proliferation and migration of gastric cancer cells. Mechanistically, UBE2C overexpression inhibited gastric cancer cell autophagy, leading to the accumulation of p62. Furthermore, immunoprecipitation results showed that UBE2C overexpression promoted the interaction between p62 and KEAP1, while inhibiting the binding of NRF2 to KEAP1, thereby weakening the ubiquitination and degradation of NRF2. In addition, the silencing of UBE2C leads to a reduction in the nuclear accumulation of NRF2. Importantly, the NRF2 activator TBHQ reversed the inhibition of gastric cancer cell proliferation and migration caused by the silencing of UBE2C. In summary, our study provides new insights into the molecular mechanisms of UBE2C in anti-cancer therapy.
胃癌（GC）是世界上最常见的恶性肿瘤之一，在恶性肿瘤的发病率中排名第四，死亡率排名第二。近年来，胃癌的生物治疗和靶向治疗取得了一定进展，但胃癌患者的预后仍然不容乐观，其涉及的分子机制尚不清楚。本研究通过生物信息学分析显示，泛素结合酶 E2C（UBE2C）在多种类型的癌症中异常表达。此外，胃癌组织和细胞中 UBE2C 蛋白和 mRNA 的表达显著升高。沉默 UBE2C 可显著抑制胃癌细胞的增殖和迁移。机制上，UBE2C 过表达抑制胃癌细胞自噬，导致 p62 积累。此外，免疫沉淀结果表明，UBE2C 过表达促进了 p62 与 KEAP1 的相互作用，同时抑制了 NRF2 与 KEAP1 的结合，从而减弱了 NRF2 的泛素化和降解。此外，UBE2C 的沉默导致 NRF2 的核积累减少。重要的是，NRF2 激活剂 TBHQ 逆转了沉默 UBE2C 引起的胃癌细胞增殖和迁移的抑制。综上所述，本研究为 UBE2C 在抗癌治疗中的分子机制提供了新的见解。
