Wu Xiaocheng, Ma Yunmiao, Cheng Ji, Li Xia, Zheng Hui, Jiang Li, Zhou Renjie
Department of Emergency, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
Departmnet of Orthopedics, Zhuji People's Hospital, Zhejiang 311800, China.
Oncotarget. 2017 Jul 28;8(45):78496-78506. doi: 10.18632/oncotarget.19655. eCollection 2017 Oct 3.
TIPE1 (tumor necrosis factor-α-induced protein 8-like 1 or TNFAIP8L1) belongs to the TIPE (TNFAIP8) family, which act as a regulator of cell death. However, the expression and biologic functions of TIPE1 in lung cancer are largely unknown. Here, we investigated the roles of TIPE1 in lung cancer. Evaluated by qRT-PCR and immunohistochemical staining, lower TIPE1 mRNA and protein expression was found in the lung tumor tissue, compared with adjacent non-tumor tissues, which positively correlated with tumor patient survival. Overexpression of TIPE1 by lentivirus system in TIPE1-downregulated lung cancer cells significantly diminished cell growth and colony formation, companied with proliferation inhibition, apoptosis induction and invasion inhibition. It was identified to be due to TIPE1-regulated Cyclin D1, Cyclin B1, caspase 8, Caspase3, MM2 and MMP9 expression. Consistently, using a homograft tumor model in Balb/c mice, we discovered that TIPE1 prevented the growth and tumor weight of murine lung cancer homografts. Our findings revealed the anti-tumor role of TIPE1 in lung cancer cells and TIPE1 might be a novel prognostic indicator for lung cancer patients.
TIPE1（肿瘤坏死因子-α诱导蛋白8样蛋白1或TNFAIP8L1）属于TIPE（TNFAIP8）家族，该家族作为细胞死亡的调节因子发挥作用。然而，TIPE1在肺癌中的表达及生物学功能在很大程度上尚不清楚。在此，我们研究了TIPE1在肺癌中的作用。通过qRT-PCR和免疫组织化学染色评估发现，与相邻的非肿瘤组织相比，肺肿瘤组织中TIPE1的mRNA和蛋白表达较低，且这与肿瘤患者的生存率呈正相关。通过慢病毒系统在TIPE1下调的肺癌细胞中过表达TIPE1，显著降低了细胞生长和集落形成，并伴有增殖抑制、凋亡诱导和侵袭抑制。经鉴定，这是由于TIPE1调节了细胞周期蛋白D1、细胞周期蛋白B1、半胱天冬酶8、半胱天冬酶3、MM2和基质金属蛋白酶9的表达。同样，在Balb/c小鼠中使用同种异体移植肿瘤模型，我们发现TIPE1可抑制小鼠肺癌同种异体移植瘤的生长和肿瘤重量。我们的研究结果揭示了TIPE1在肺癌细胞中的抗肿瘤作用，且TIPE1可能是肺癌患者的一种新型预后指标。
