Department of Oral Medicine, The First Affiliated Hospital of Zhengzhou University, #1 LongHuZhongHuan Rd., JinShuiQu, Zhengzhou 450000, China.
J Biochem. 2021 Sep 7;169(6):721-730. doi: 10.1093/jb/mvab026.
Long non-coding RNAs (lncRNAs) have been considered as novel regulators in oral squamous cell carcinoma (OSCC). Enhancer of zeste homolog 2 (EZH2) can act as an oncogene in OSCC. This study intended to investigate whether lncRNA prostatic androgen-regulated transcription 1 (PART1) can exert its role in OSCC by regulating EZH2. The expression of PART1 in OSCC samples, tumour tissues or OSCC cell lines was detected by qRT-PCR. The proliferation and apoptosis of OSCC cells were detected by CCK-8 and flow cytometry assays, respectively. The expression of PART1 and EZH2 was highly expressed in clinical OSCC tumours and cell lines. The expression level of PART1 was positively correlated to the size, clinical stage and node metastasis of OSCC patients. Functionally, PART1 knockdown inhibited proliferation and facilitated apoptosis of OSCC cells. Mechanically, fused in sarcoma/translocated in liposarcoma (FUS) interacted with PART1 and EZH2. In addition, PART1 knockdown reduced the mRNA expression of EZH2, which was offset by FUS overexpression. The overexpression of FUS abrogated the effects of PART1 silence on proliferation and apoptosis of OSCC cells. The in vivo experiment revealed that PART1 knockdown inhibited tumour growth of OSCC cells in nude mice. This study indicated that PART1 exerts a carcinogenic role in OSCC by enhancing the stability of EZH2 protein.
长链非编码 RNA（lncRNA）被认为是口腔鳞状细胞癌（OSCC）中的新型调节因子。EZH2 可以作为 OSCC 中的癌基因。本研究旨在探讨 lncRNA 前列腺雄激素调节转录物 1（PART1）是否可以通过调节 EZH2 在 OSCC 中发挥作用。通过 qRT-PCR 检测 OSCC 样本、肿瘤组织或 OSCC 细胞系中 PART1 的表达。通过 CCK-8 和流式细胞术分别检测 OSCC 细胞的增殖和凋亡。PART1 和 EZH2 在临床 OSCC 肿瘤和细胞系中高表达。PART1 的表达水平与 OSCC 患者的肿瘤大小、临床分期和淋巴结转移呈正相关。功能上，PART1 敲低抑制 OSCC 细胞的增殖并促进其凋亡。机制上，肉瘤融合/脂肪肉瘤易位（FUS）与 PART1 和 EZH2 相互作用。此外，PART1 敲低降低了 EZH2 的 mRNA 表达，而 FUS 过表达则抵消了这一作用。FUS 的过表达消除了 PART1 沉默对 OSCC 细胞增殖和凋亡的影响。体内实验表明，PART1 敲低抑制了裸鼠 OSCC 细胞的肿瘤生长。本研究表明，PART1 通过增强 EZH2 蛋白的稳定性在 OSCC 中发挥致癌作用。
