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Long non-coding RNA IRAIN suppresses apoptosis and promotes proliferation by binding to LSD1 and EZH2 in pancreatic cancer

机译:长的非编码RNA IRAIN通过与LSD1和EZH2结合来抑制胰腺癌的凋亡并促进增殖

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摘要

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.
机译:长的非编码RNA(lncRNA)调节基因表达,而lncRNA失调与人类癌症有关。此外,尽管最近的研究表明lncRNA IRAIN在其他恶性肿瘤中起重要作用,但IRAIN在胰腺癌(PC)进展中的作用仍不清楚。在这项研究中,我们发现在一组37例PC患者中,lncRNA IRAIN的上调与肿瘤大小,TNM分期和淋巴结转移显着相关。体外实验表明,通过小干扰RNA(siRNA)抑制IRAIN可以显着诱导BxPC-3和PANC-1细胞的细胞凋亡并抑制细胞增殖。进一步的机制研究表明,通过结合组蛋白脱甲基酶赖氨酸特异性脱甲基酶1(LSD1),zeste同源物2(EZH2)的增强剂,IRAIN通过沉默Kruppel样因子2的表达来减少PC肿瘤细胞凋亡并诱导生长停滞。 (KLF2)和P15。此外,IRAIN表达与PC组织中KLF2和P15的表达呈负相关。据我们所知,这是第一个阐明IRAIN在PC进程中的作用和机制的报告。

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