Department of Gastroenterology, Zhongshan Hospital affiliated to Xiamen University, Xiamen, 361004, Fujian, People's Republic of China.
Department of Oncology, Second Affiliated Hospital, Nanjing Medical University, Nanjing, 210000, Jiangsu, People's Republic of China.
Sci Rep. 2017 Aug 4;7(1):7312. doi: 10.1038/s41598-017-07954-7.
Recently, substantial evidence has demonstrated that pseudogene derived lncRNAs are crucial regulators of cancer development and progression. DUXAP10,a pseudogene derived long non-coding RNA(lncRNA), is overexpression in colorectal cancer (CRC), but its expression pattern, biological function and underlying mechanism in CRC is still undetermined. In this study, we observed that DUXAP10 was up-regulated in CRC tissues which was positively correlated with advanced pathological stages, larger tumor sizes and lymph node metastasis. Additionally, knockdown of DUXAP10 inhibited cell proliferation, induced cell apoptosis and increase the number of G0/G1 cells significantly in the HCT116 and SW480 cell lines. Moreover, DUXAP10 silencing inhibited tumor growth in vivo. Further mechanism study showed that, by binding to histone demethylase lysine-specific demethylase 1 (LSD1), DUXAP10 promote CRC cell growth and reduced cell apoptosis through silencing the expression of p21 and phosphatase and tensin homolog (PTEN) tumor suppressor. Our findings suggested that the pseudogene-derived from lncRNA DUXAP10 promotes the biological progression of CRC and is likely to be a potential therapeutic target for CRC intervention.
最近，大量证据表明假基因衍生的长非编码 RNA（lncRNA）是癌症发生和发展的重要调节因子。DUXAP10 是一个假基因衍生的长非编码 RNA（lncRNA），在结直肠癌（CRC）中过表达，但它在 CRC 中的表达模式、生物学功能和潜在机制尚不清楚。在本研究中，我们观察到 DUXAP10 在 CRC 组织中上调，与晚期病理阶段、更大的肿瘤大小和淋巴结转移呈正相关。此外，在 HCT116 和 SW480 细胞系中，敲低 DUXAP10 显著抑制细胞增殖，诱导细胞凋亡，并增加 G0/G1 期细胞数量。此外，DUXAP10 沉默抑制体内肿瘤生长。进一步的机制研究表明，通过与组蛋白去甲基化酶赖氨酸特异性去甲基酶 1（LSD1）结合，DUXAP10 通过沉默抑癌基因 p21 和磷酸酶和张力蛋白同源物（PTEN）的表达，促进 CRC 细胞生长和减少细胞凋亡。我们的研究结果表明，假基因衍生的 lncRNA DUXAP10 促进 CRC 的生物学进展，可能是 CRC 干预的潜在治疗靶点。
