Men Xuelin, Wang Lingcheng, Yu Wenfei, Ju Yuanrong
Department of Respiratory, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, P.R. China.
Oncol Res. 2015;22(2):123-8. doi: 10.3727/096504014X14198596979742.
Ubiquitin ligase Cullin7 has been identified as an oncogene in some malignant diseases such as choriocarcinoma and neuroblastoma. However, the role of Cullin7 in lung cancer carcinogenesis remains unclear. In this study, we explored the functional role of Cullin7 in lung cancer cell proliferation and tumorigenesis and determined its expression profile in lung cancer. Knocking down Cullin7 expression by small interfering RNA (siRNA) in lung cancer cells inhibited cell proliferation and elevated the expression of p53, p27, and p21 proteins. The enhanced p53 expression resulted from activation of the DNA damage response pathway. Cullin7 knockdown markedly suppressed xenograft tumor growth in vivo in mice. Moreover, Cullin7 expression was increased in primary lung cancer tissues of humans. Thus, Cullin7 is required for sustained proliferation and survival of tumor cells in vitro and in vivo, and its aberrant expression may contribute to the pathogenesis of lung cancer. Thus, our study provided evidence that Cullin7 functions as a novel oncogene in lung cancer and may be a potential therapeutic target for lung cancer management.
泛素连接酶Cullin7已被确定为某些恶性疾病（如绒毛膜癌和神经母细胞瘤）中的一种癌基因。然而，Cullin7在肺癌发生中的作用仍不清楚。在本研究中，我们探讨了Cullin7在肺癌细胞增殖和肿瘤发生中的功能作用，并确定了其在肺癌中的表达谱。通过小干扰RNA（siRNA）敲低肺癌细胞中Cullin7的表达可抑制细胞增殖，并提高p53、p27和p21蛋白的表达。p53表达的增强是由DNA损伤反应途径的激活导致的。Cullin7基因敲低显著抑制了小鼠体内异种移植肿瘤的生长。此外，人类原发性肺癌组织中Cullin7的表达增加。因此，Cullin7是肿瘤细胞在体外和体内持续增殖和存活所必需的，其异常表达可能与肺癌的发病机制有关。因此，我们的研究提供了证据表明Cullin7在肺癌中作为一种新的癌基因发挥作用，并且可能是肺癌治疗的潜在靶点。
