作为治疗靶点的癌症维持基因。

Cancer-keeper genes as therapeutic targets.

作者信息

Zhang Xizhe, Pan Chunyu, Wei Xinru, Yu Meng, Liu Shuangjie, An Jun, Yang Jieping, Wei Baojun, Hao Wenjun, Yao Yang, Zhu Yuyan, Zhang Weixiong

机构信息

Early Intervention Unit, Department of Psychiatry, The Affiliated Brain Hospital of Nanjing Medical University, Nanjing, China.

School of Biomedical Engineering and Informatics, Nanjing Medical University, Nanjing, China.

出版信息

iScience. 2023 Jul 11;26(8):107296. doi: 10.1016/j.isci.2023.107296. eCollection 2023 Aug 18.

Finding cancer-driver genes has been a central theme of cancer research. We took a different perspective; instead of considering normal cells, we focused on cancerous cells and genes that maintained abnormal cell growth, which we named cancer-keeper genes (CKGs). Intervening CKGs may rectify aberrant cell growth, making them potential cancer therapeutic targets. We introduced genes and developed an efficient algorithm by extending network controllability theory. Control hub are essential for maintaining cancerous states and thus can be taken as CKGs. We applied our CKG-based approach to bladder cancer (BLCA). All genes on the cell-cycle and p53 pathways in BLCA were identified as CKGs, showing their importance in cancer. We discovered that sensitive CKGs - genes easily altered by structural perturbation - were particularly suitable therapeutic targets. Experiments on cell lines and a mouse model confirmed that six sensitive CKGs effectively suppressed cancer cell growth, demonstrating the immense therapeutic potential of CKGs.

寻找癌症驱动基因一直是癌症研究的核心主题。我们采取了不同的视角；我们没有考虑正常细胞，而是专注于癌细胞以及维持异常细胞生长的基因，我们将其命名为癌症维持基因（CKGs）。干预癌症维持基因可能会纠正异常的细胞生长，使其成为潜在的癌症治疗靶点。我们引入了相关基因，并通过扩展网络可控性理论开发了一种高效算法。控制枢纽对于维持癌症状态至关重要，因此可被视为癌症维持基因。我们将基于癌症维持基因的方法应用于膀胱癌（BLCA）。膀胱癌中细胞周期和p53途径上的所有基因都被鉴定为癌症维持基因，显示出它们在癌症中的重要性。我们发现，敏感的癌症维持基因——容易因结构扰动而改变的基因——是特别合适的治疗靶点。在细胞系和小鼠模型上进行的实验证实，六个敏感的癌症维持基因有效地抑制了癌细胞的生长，证明了癌症维持基因具有巨大的治疗潜力。