Lian Yifan, Wang Juan, Feng Jing, Ding Jie, Ma Zhonghua, Li Juan, Peng Peng, De Wei, Wang Keming
Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China.
Department of Oncology, First Affiliated Hospital of Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China.
Tumour Biol. 2016 Nov;37(11):14929-14937. doi: 10.1007/s13277-016-5380-8. Epub 2016 Sep 19.
Long non-coding RNA (lncRNA) modulates gene expression, while lncRNA dysregulation is associated with human cancer. Furthermore, while recent studies have shown that lncRNA IRAIN plays an important role in other malignancies, the role of IRAIN in pancreatic cancer (PC) progression remains unclear. In this study, we found that upregulation of lncRNA IRAIN was significantly correlated with tumor size, TNM stage, and lymph node metastasis in a cohort of 37 PC patients. In vitro experiments showed that knockdown of IRAIN by small interfering RNA (siRNA) significantly induced cell apoptosis and inhibited cell proliferation in both BxPC-3 and PANC-1 cells. Further mechanism study showed that, by binding to histone demethylase lysine-specific demethylase 1 (LSD1), an enhancer of zeste homolog 2 (EZH2), IRAIN reduced PC tumor cell apoptosis and induced growth arrest by silencing the expression of Kruppel-like factor 2 (KLF2) and P15. Moreover, IRAIN expression was inversely correlated with that of KLF2 and P15 in PC tissues. To our knowledge, this is the first report elucidating the role and mechanism of IRAIN in PC progression.
长链非编码RNA（lncRNA）可调节基因表达，而lncRNA失调与人类癌症相关。此外，尽管最近的研究表明lncRNA IRAIN在其他恶性肿瘤中发挥重要作用，但IRAIN在胰腺癌（PC）进展中的作用仍不清楚。在本研究中，我们发现lncRNA IRAIN的上调与37例PC患者队列中的肿瘤大小、TNM分期和淋巴结转移显著相关。体外实验表明，通过小干扰RNA（siRNA）敲低IRAIN可显著诱导BxPC-3和PANC-1细胞凋亡并抑制细胞增殖。进一步的机制研究表明，IRAIN通过与组蛋白去甲基化酶赖氨酸特异性去甲基化酶1（LSD1）、zeste同源物2增强子（EZH2）结合，沉默Kruppel样因子2（KLF2）和P15的表达，从而减少PC肿瘤细胞凋亡并诱导生长停滞。此外，在PC组织中，IRAIN的表达与KLF2和P15的表达呈负相关。据我们所知，这是首次阐明IRAIN在PC进展中的作用和机制的报告。
