MEG3, HCN3 and linc01105 influence the proliferation and apoptosis of neuroblastoma cells via the HIF-1α and p53 pathways.
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.
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China.
Weitao
W
Tang
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China.
Kuiran
K
Dong
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China.
Kai
K
Li
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China.
Rui
R
Dong
Department of Pediatric Surgery, Children's Hospital of Fudan University, Shanghai, China.
Shan
S
Zheng
D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000235:genetics*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics* / Q000378:metabolism; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D015221:Potassium Channels / Q000235:genetics*; D062085:RNA, Long Noncoding / Q000235:genetics*; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
C472018:HCN3 protein, human; C497442:HIF1A protein, human; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; C498907:MEG3 non-coding RNA, human; D015221:Potassium Channels; D062085:RNA, Long Noncoding; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53