Tian Binle, Zhou Jingyi, Chen Guiming, Jiang Tao, Li Qi, Qin Jian
Department of Oncology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of General Surgery, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Front Oncol. 2022 Aug 17;12:906281. doi: 10.3389/fonc.2022.906281. eCollection 2022.
Colorectal cancer (CRC), one of the cancers with highest mortality, involves complicated molecular mechanisms leading to the onset of malignant phenotypes. ZNF280A, a member of the zinc-finger protein family, was shown to be a promotor of oncogenesis in CRC in this study. ZNF280A was remarkably upregulated in CRC tissues, which was meaningfully associated with tumor progression and poor prognosis in patients with CRC. Loss-of-function studies revealed that ZNF280A knockdown inhibited the development and progression of CRC as evident by the inhibition of cell proliferation, colony formation, cell apoptosis, cell cycle distribution, and cell migration and the repressed tumorigenesis of CRC cells . Next, we showed that RPS14 was the downstream target of ZNF280A and ZNF280A knockdown promoted the ubiquitination as well as degradation of RPS14 in CRC. Additionally, we demonstrated that RPS14 regulated the development of CRC PI3K-Akt signaling pathway. Taken together, our findings provide a novel clear insight into ZNF280A/RPS14/PI3K-Akt axis in CRC for the first time, offering a potential target for early detection, diagnosis and treatment of CRC in future clinical applications.
结直肠癌（CRC）是死亡率最高的癌症之一，涉及导致恶性表型发生的复杂分子机制。在本研究中，锌指蛋白家族成员ZNF280A被证明是结直肠癌肿瘤发生的促进因子。ZNF280A在结直肠癌组织中显著上调，这与结直肠癌患者的肿瘤进展和不良预后密切相关。功能丧失研究表明，ZNF280A基因敲低可抑制结直肠癌的发展和进展，这可通过抑制细胞增殖、集落形成、细胞凋亡、细胞周期分布和细胞迁移以及抑制结直肠癌细胞的肿瘤发生来证明。接下来，我们发现RPS14是ZNF280A的下游靶点，ZNF280A基因敲低可促进结直肠癌中RPS14的泛素化以及降解。此外，我们证明RPS14通过PI3K-Akt信号通路调节结直肠癌的发展。综上所述，我们的研究结果首次为结直肠癌中的ZNF280A/RPS14/PI3K-Akt轴提供了全新的清晰见解，为未来临床应用中结直肠癌的早期检测、诊断和治疗提供了潜在靶点。
