MEG3, HCN3 and linc01105 influence the proliferation and apoptosis of neuroblastoma cells via the HIF-1α and p53 pathways

Abstract

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.

Differential expression and prognostic value of long non‐coding RNA in HPV‐negative head and neck squamous cell carcinoma

“…MEG3 is a lncRNA located at the DLK-MEG3 locus on chromosome 14q32.3 and is reported to be a tumor suppressor gene, exerting its effect in part through interaction with tumor suppressor and master regulator p53. 26,27 MEG3 has been reported to be downregulated in multiple solid tumor types, 28 which is consistent with what we observed in our 19 HPV-negative HNSCC tumor-adjacent normal pairs. However, our observed association of low MEG3 expression with better 3-year RFS is contrary to what has been reported for other solid tumor types 29 and, therefore, should be interpreted with caution.…”

“…MEG3 is a lncRNA located at the DLK‐MEG3 locus on chromosome 14q32.3 and is reported to be a tumor suppressor gene, exerting its effect in part through interaction with tumor suppressor and master regulator p53 . MEG3 has been reported to be downregulated in multiple solid tumor types, which is consistent with what we observed in our 19 HPV‐negative HNSCC tumor‐adjacent normal pairs.…”

A group of long noncoding RNAs identified by data mining can predict the prognosis of lung adenocarcinoma

“…LOC150622 (LINC01105) is a stage‐specific biomarker in lung adenocarcinoma. It is also highly expressed in neuroblastoma tissue, where it affects cellular proliferation and apoptosis . Methylation of the LOC284276 (LINC00908) gene is negatively associated with birth weight .…”

“…It is also highly expressed in neuroblastoma tissue, where it affects cellular proliferation and apoptosis. 37,38 Methylation of the LOC284276 (LINC00908) gene is negatively associated with birth weight. 39 NCRNA00092 (LINC00092) acts in cancer-associated fibroblasts to drive glycolysis and progression of ovarian cancer.…”

Neuroblastoma: Genetic, Epigenetic Mechanisms and Targeted Therapy Approaches: Review

“…Öte yandan, yine TP53 yolağında bulunan proapoptotik lncRNA MEG3' ün aşağı regülasyonu apoptozun baskılan-masına ve nöroblastom dokularında farklılaşmanın bozulmasına yol açar. 66 Genetik ve epigenetik değişikliklere dair bilgiler artmakla birlikte, mekanizmaların tam olarak nasıl işlediği hâlâ keşfedilmeyi beklemektedir (Şekil 2).…”