Ge Wen'an, Wang Shengxing
Department of Urology, Xi'an Children's Hospital Xi'an 710003 China
RSC Adv. 2019 Dec 4;9(69):40240-40247. doi: 10.1039/c9ra07215b. eCollection 2019 Dec 3.
Wilms tumor (nephroblastoma) is the most common primary renal tumor occurring in children. Long noncoding RNA (lncRNA) deleted in lymphocytic leukemia 1 (DLEU1) is an identified cancer-associated lncRNA that plays an important role in various cancers. However, the role of DLEU1 in Wilms tumor remains unclear. In the present study, we examined the expression and role of DLEU1 in Wilms tumor. We demonstrated that DLEU1 expression was upregulated in Wilms tumor tissues and cell lines. Knockdown of DLEU1 significantly inhibited the proliferation, migration and invasion of GHINK-1 cells. Furthermore, DLEU1 directly sponged miR-300 and regulated the expression level of miR-300 in GHINK-1 cells. Inhibition of miR-300 reversed the inhibitory effects of DLEU1 downregulation on cell proliferation, migration and invasion. Homeobox C8 (HOXC8) was found to be a target gene of miR-300 and mediated the role of miR-300 in GHINK-1 cells. In conclusion, these findings indicated that DLEU1 executed an oncogenic role in Wilms tumor regulating the miR-300/HOXC8 axis, indicating that DLEU1 might be a therapeutic target for the treatment of Wilms tumor.
肾母细胞瘤是儿童中最常见的原发性肾脏肿瘤。淋巴细胞白血病1(DLEU1)中缺失的长链非编码RNA(lncRNA)是一种已确定的与癌症相关的lncRNA,在多种癌症中发挥重要作用。然而,DLEU1在肾母细胞瘤中的作用仍不清楚。在本研究中,我们检测了DLEU1在肾母细胞瘤中的表达及作用。我们发现,DLEU1在肾母细胞瘤组织和细胞系中表达上调。敲低DLEU1可显著抑制GHINK-1细胞的增殖、迁移和侵袭。此外,DLEU1直接吸附miR-300并调节GHINK-1细胞中miR-300的表达水平。抑制miR-300可逆转DLEU1下调对细胞增殖、迁移和侵袭的抑制作用。发现同源盒C8(HOXC8)是miR-300的靶基因,并介导miR-300在GHINK-1细胞中的作用。总之,这些发现表明DLEU1通过调节miR-300/HOXC8轴在肾母细胞瘤中发挥致癌作用,提示DLEU1可能是肾母细胞瘤治疗的一个靶点。