Department of Gastroenterology, Zhongshan Hospital, Xiamen University, Xiamen, Fujian, China.
Institute for Microbial Ecology, Xiamen University, Xiamen, Fujian, China.
J Cell Biochem. 2018 Apr;119(4):3671-3682. doi: 10.1002/jcb.26578. Epub 2018 Jan 5.
Current evidence suggests that pseudogene derived lncRNAs may be important players in human cancer progression. Our previous study showed that DUXAP10 could promote cell proliferation in colorectal cancer. However, the clinical significance and potential role of DUXAP10 in human pancreatic cancer (PC) has not been uncovered. In this study, we found that DUXAP10 was overexpressed in PC tissues compared with normal tissues. DUXAP10 expression was significantly higher in patients with an advanced TNM stage and positive lymph node metastasis. Bioinformatic analysis showed that cell cycle progression was increased in patients with high DUXAP10 expression. In vitro and in vivo assays of DUXAP10 alterations revealed a complex integrated phenotype affecting cell growth, apoptosis, migration, and invasion. Mechanistic studies revealed that DUXAP10 has a crucial role in G2/M arrest. We further showed that DUXAP10 regulated PC cell proliferation through interact with RNA-binding protein EZH2 and LSD1. Overall, our findings indicates that DUXAP10 is an oncogenic lncRNA that promotes PC proliferation and metastasis.
目前的证据表明，假基因衍生的长非编码 RNA 可能是人类癌症进展的重要参与者。我们之前的研究表明，DUXAP10 可以促进结直肠癌细胞的增殖。然而，DUXAP10 在人类胰腺癌（PC）中的临床意义和潜在作用尚未被揭示。在这项研究中，我们发现 DUXAP10 在 PC 组织中的表达高于正常组织。在 TNM 分期较晚和有阳性淋巴结转移的患者中，DUXAP10 的表达明显更高。生物信息学分析显示，高 DUXAP10 表达的患者细胞周期进展增加。对 DUXAP10 改变的体外和体内检测显示，一种复杂的综合表型影响细胞生长、凋亡、迁移和侵袭。机制研究表明，DUXAP10 在 G2/M 期阻滞中起着关键作用。我们进一步表明，DUXAP10 通过与 RNA 结合蛋白 EZH2 和 LSD1 相互作用来调节 PC 细胞的增殖。总的来说，我们的研究结果表明，DUXAP10 是一种致癌的长非编码 RNA，它促进 PC 的增殖和转移。
