Zhang Cheng-Lin, Wang Ce, Yan Wang-Jun, Gao Rui, Li Yong-Hua, Zhou Xu-Hui
Department of Orthopedic Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Department of Anesthesiology, Changzheng Hospital, Second Military Medical University, Shanghai 200003, P.R. China.
Oncol Rep. 2014 Sep;32(3):1149-55. doi: 10.3892/or.2014.3291. Epub 2014 Jun 25.
Tumor necrosis factor-α-inducible protein-1 (TNFAIP1) plays a role in DNA synthesis, DNA repair, cell apoptosis and human diseases including cancer, and may be involved in tumor progression and metastases. However, little is known concerning the function of TNFAIP1 in human osteosarcoma (OS). The aim of the present study was to investigate the function and underlying mechanisms of TNFAIP1 in human OS. The expression of TNFAIP1 was examined by immunohistochemical assay using a tissue microarray procedure. A loss-of-function experiment was performed to explore the effects of lentiviral-mediated TNFAIP1 siRNA (siTNFAIP1) on cell proliferation, invasive potential and apoptosis by MTT and Transwell assays and flow cytometric analysis in OS (MG-63 and U-2 OS) cells. The results showed that the expression of TNFAIP1 protein was significantly increased in OS tissues compared with that in adjacent non-cancerous tissues (ANCTs) (73.3 vs. 48.9%, P=0.018), and was correlated with the distant metastasis of the patients with OS (P=0.029). Knockdown of TNFAIP1 suppressed cell proliferation and invasion, and induced cell apoptosis in the OS cells together with the downregulation of p65 nuclear factor-κB (NF-κB), proliferating cell nuclear antigen (PCNA) and matrix metalloproteinase-2 (MMP-2) and upregulation of caspase-3. Collectively, our findings indicate that high expression of TNFAIP1 is associated with distant metastasis of OS, and knockdown of TNFAIP1 inhibits the growth and invasion, and induces apoptosis in OS cells through inhibition of the NF-κB pathway, suggesting that TNFAIP1 may act as a potential therapeutic target for the treatment of cancer.
肿瘤坏死因子-α诱导蛋白1（TNFAIP1）在DNA合成、DNA修复、细胞凋亡以及包括癌症在内的人类疾病中发挥作用，并且可能参与肿瘤进展和转移。然而，关于TNFAIP1在人类骨肉瘤（OS）中的功能知之甚少。本研究的目的是探讨TNFAIP1在人类OS中的功能及潜在机制。采用组织芯片技术通过免疫组织化学分析检测TNFAIP1的表达。进行功能缺失实验，通过MTT法、Transwell实验和流式细胞术分析，探讨慢病毒介导的TNFAIP1小干扰RNA（siTNFAIP1）对OS（MG-63和U-2 OS）细胞增殖、侵袭潜能和凋亡的影响。结果显示，与相邻非癌组织（ANCTs）相比，TNFAIP1蛋白在OS组织中的表达显著增加（73.3%对48.9%，P=0.018），并且与OS患者的远处转移相关（P=0.029）。敲低TNFAIP1可抑制OS细胞的增殖和侵袭，并诱导细胞凋亡，同时下调p65核因子-κB（NF-κB）、增殖细胞核抗原（PCNA）和基质金属蛋白酶-2（MMP-2），上调半胱天冬酶-3。总体而言，我们的研究结果表明，TNFAIP1的高表达与OS的远处转移相关，敲低TNFAIP1可抑制OS细胞的生长和侵袭，并通过抑制NF-κB途径诱导细胞凋亡，提示TNFAIP1可能作为癌症治疗的潜在靶点。
