Wang Xing, Jiang Li
Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong 510080, P.R. China.
Int J Mol Med. 2014 Dec;34(6):1606-12. doi: 10.3892/ijmm.2014.1961. Epub 2014 Oct 10.
Ornithine decarboxylase antizyme 1 (OAZ1) is an antizyme targeting ornithine decarboxylase for degradation, subsequently inhibiting polyamine production to prevent cell proliferation. OAZ1 is also involved in other major cellular events, including differentiation and apoptosis. Recent studies have shown that OAZ1 has tumor suppressor activities and its effects on cell proliferation and differentiation have been reported in several cancer cell lines. To explore the role of OAZ1 in human oral cancer, the effects of OAZ1 were studied on the proliferation and differentiation of human malignant oral cancer cell line, SCC15. MTT assay and flow cytometry analysis showed that stable OAZ1 expression in SCC15 significantly inhibited cell proliferation (P<0.001) and induced G0/G1 arrest with the G1‑phase cells increased from 55.83 to 65.26%. Morphological observation revealed the increased formation of epithelial islands. Further results from quantitative reverse transcription‑polymerase chain reaction and western blot analysis proved the upregulation of several terminal differentiation marker genes (K10, FLG and LOR) in OAZ1‑expressed SCC15 cells. To elucidate the possible mechanism of LOR upregulation by OAZ1, further experiments were performed and it was found that the OAZ1 expression inhibited Smad nuclear interacting protein 1 (SNIP1) at the protein level and RNA interference of SNIP1 in SCC15 cells, which increased the expression of LOR. These results show that OAZ1 simultaneously inhibits the proliferation and induces the differentiation of oral cancer cells in humans. The effects on cellular differentiation depend partly on the degradation of SNIP1.
鸟氨酸脱羧酶抗酶1（OAZ1）是一种靶向鸟氨酸脱羧酶进行降解的抗酶，随后抑制多胺生成以阻止细胞增殖。OAZ1还参与其他主要的细胞活动，包括分化和凋亡。最近的研究表明，OAZ1具有肿瘤抑制活性，并且其对细胞增殖和分化的影响已在多种癌细胞系中得到报道。为了探究OAZ1在人类口腔癌中的作用，研究了OAZ1对人类恶性口腔癌细胞系SCC15增殖和分化的影响。MTT法和流式细胞术分析表明，SCC15中稳定表达OAZ1可显著抑制细胞增殖（P<0.001），并诱导G0/G1期阻滞，G1期细胞从55.83%增加到65.26%。形态学观察显示上皮岛形成增加。定量逆转录-聚合酶链反应和蛋白质印迹分析的进一步结果证明，在表达OAZ1的SCC15细胞中，几种终末分化标记基因（K10、FLG和LOR）上调。为了阐明OAZ1上调LOR的可能机制，进行了进一步实验，发现OAZ1表达在蛋白质水平抑制Smad核相互作用蛋白1（SNIP1），并且在SCC15细胞中对SNIP1进行RNA干扰可增加LOR的表达。这些结果表明，OAZ1同时抑制人类口腔癌细胞的增殖并诱导其分化。对细胞分化的影响部分取决于SNIP1的降解。
