Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China.
Sci Rep. 2016 Nov 8;6:36268. doi: 10.1038/srep36268.
The purpose of this study was to investigate the differential expression and functional roles of long non-coding RNAs (lncRNAs) in neuroblastoma tissue. LncRNA microarrays were used to identify differentially expressed lncRNAs between tumor and para-tumor tissues. In total, in tumor tissues, 3,098 and 1,704 lncRNAs were upregulated and downregulated, respectively. HCN3 and linc01105 exhibited the higher expression (P < 0.05; P < 0.01, respectively) in neuroblastoma tissue, whereas MEG3 displayed the lower expression (P < 0.01). HIF-1α expression was negatively correlated with cell proliferation in the linc01105 KD group. In addition, Noxa and Bid expression was positively correlated with cell apoptosis. Moreover, linc01105 knockdown promoted cell proliferation, whereas MEG3 overexpression inhibited proliferation. Finally, linc01105 knockdown, MEG3 overexpression and HCN3 knockdown all increased apoptosis. The correlation coefficients between those three lncRNAs and the International Neuroblastoma Staging System (INSS) stage were -0.48, -0.58 and -0.55, respectively. In conclusion, we have identified lncRNAs that are differentially expressed in neuroblastoma tissues. The lncRNAs HCN3, linc01105, and MEG3 may be important in biological behaviors of neuroblastoma through mechanisms involving p53 pathway members such as HIF-1α, Noxa, and Bid. The expressions of MEG3, HCN3 and linc01105 are all negatively correlated with the INSS stage.
本研究旨在探讨长链非编码 RNA(lncRNAs)在神经母细胞瘤组织中的差异表达和功能作用。采用 lncRNA 微阵列技术鉴定肿瘤组织与癌旁组织之间差异表达的 lncRNAs。结果显示,肿瘤组织中分别有 3098 个和 1704 个 lncRNAs 上调和下调。在神经母细胞瘤组织中,HCN3 和 linc01105 表达较高(P<0.05;P<0.01),而 MEG3 表达较低(P<0.01)。HIF-1α 的表达与 linc01105 KD 组细胞增殖呈负相关。此外,Noxa 和 Bid 的表达与细胞凋亡呈正相关。此外,linc01105 敲低促进细胞增殖,而 MEG3 过表达抑制增殖。最后,linc01105 敲低、MEG3 过表达和 HCN3 敲低均增加细胞凋亡。这 3 个 lncRNA 与国际神经母细胞瘤分期系统(INSS)分期的相关系数分别为-0.48、-0.58 和-0.55。综上所述,我们已经鉴定出神经母细胞瘤组织中差异表达的 lncRNAs。lncRNA HCN3、linc01105 和 MEG3 可能通过涉及 HIF-1α、Noxa 和 Bid 等 p53 途径成员的机制,在神经母细胞瘤的生物学行为中发挥重要作用。MEG3、HCN3 和 linc01105 的表达均与 INSS 分期呈负相关。