Table 4.
Up-regulated lncRNAs in neuroblastoma (ANT, adjacent normal tissue; NB, Neuroblastoma; EMT, epithelial-mesenchymal transition; OS, overall survival; EFS, event-free survival).
| lncRNA | Specimens | Cell lines | Targets/regulators | Signaling pathway | Function | Effect of lncRNA up-regulation on patient’s prognosis | Ref |
|---|---|---|---|---|---|---|---|
| DLX6AS1 | 70 pairs of primary NB and ANTs | SK-N-SH, SH-SY5Y, SK-N-AS, SK-N-BE, HEK293T | miR-497-5p, YAP1 | – | DLX6-AS1 knock-down results in diminished proliferation rate, tumor proliferation, migration, EMT, and invasion. | Poor prognosis and OS | (90) |
| 31 NB and ANTs | SK-N-SH, LAN-6, HUVEC | miR-506-3p, STAT2, CDK1, Cyclin D1 | – | DLX6-AS1 silencing inhibits proliferation, tumor growth, cell cycle, and glycolysis. | – | (91) | |
| lncNB1 | SEQC-RPM-seqcnb1 dataset: 493 NB tissues | BE(2)-C, IMR32, SY5Y, SHEP, HEK293T | RPL35, E2F1, DEPDC1B, ERK, n-Myc | – | LncNB1 down-regulation abrogates clonogenic capacity and leads to NB tumor regression. | Lower OS | (92) |
| DEIN | Case study of a monozygotic twin with NB | – | HAND2 | – | Both twin liver tumors had a 4q34.1 amplification of DEIN, which is strongly linked to HAND2. HAND2 functions as an essential regulator of neurogenesis. | – | (93) |
| LINC01296 | 28 patients with primary NB, R2: Genomics Analysis and Visualization Platform for 88 NB patients |
– | – | – | Over-expression of LINC01296 was associated with age>18 month and advanced INSS stage. Moreover, LINC01296 over-expression is correlated with larger tumor size, elevated serum lactate dehydrogenase level, and serum neuron-specific enolase level. | Poor prognosis and OS | (94) |
| SNHG16 | 40 patients with NB, GSE62564 dataset: 498 NB patients | SH-SY5Y | – | – | SNHG16 down-regulation inhibits proliferation, migration, and induces cell cycle arrest at the G0/G1 phase. SNHG16-related RNA binding proteins partake in controlling mRNA metabolic processes, gene silencing, mRNA transport, RNA splicing, and translation. | Poor OS and EFS | (95) |
| 76 NB tissues | SK-N-AS, SK-N-SH, SK-N-AS-R, SK-NSH-R | miR-338-3p, PLK4, MRP1, p-glycoprotein | PI3K/AKT | In cisplatin-resistant NB tissues and cells. SNHG16 is up-regulated, while miR-338-3p is down-regulated. | – | (96) | |
| 48 NB and 38 ANTs | SK-N-SH, IMR‐32, SK-N-AS, SK-N-DZ, HUVEC | HOXA7, miR-128-3p | – | SNHG16 silencing represses proliferation, migration, and invasion but boosts apoptosis. |
– | (97) | |
| 30 NB and 30 ANTs | SKNBE-2, SK-N-SH, HEK293, LAN-5 | miR-542-3p, HNF4α | RAS/RAF/MEK/ERK | The Knock-down of SNHG16 or HNF4α impedes proliferation, migration, invasion, and EMT. | – | (98) | |
| 45 NB and ANTs | LAN-1, SHEP, SKN-SH, IMR-32, HUVEC | miR-542-3p, ATG5 | – | The knock-down of SNHG16 diminishes proliferation, migration, invasion, autophagy, and tumor growth. | Lower OS | (99) | |
| MIAT | – | Neuro2A | caspase-3, miR-211, GDNF | – | MIAT overexpression lowers the apoptosis rate. | – | (100) |
| SNHG7 | miR-653-5p, STAT2 | SNHG7-miR‐653‐5p‐STAT2 loop is involved in regulation of NB progression. | (101) | ||||
| 26 NB and ANTs | SK-N-AS, LAN-6, HUVEC | miR-329-3p, MYO10 | – | Silencing of SNHG7 reduced cisplatin resistance and suppressed cisplatin-induced autophagy. | – | (102) | |
| 45 NB and ANTs | SH-SY5Y, SK-N-SH, NB-1, SK-N-AS, HUVEC | miR-323a-5p, miR-342-5p, CCND1 | – | SNHG7 knock down repressed migration, invasion, and glycolysis. | Poor prognosis and OS | (103) | |
| RMRP | 44 cases of neonatal NB and ANTs | NB-1, SK-N-AS, HEK293T | miR-206, TACR1 | ERK1/2 | RMRP knock-down lessens proliferation, migration, and invasion rates. RMRP expression is markedly increased in patients with advanced neonatal NB versus early stages. | Poor OS | (104) |
| SNHG1 | – | SK-N-DZ, SK-N-BE(2)C, SK-N-AS | MATR3, YBX1, HNRNPL | – | SNHG1 significantly elevates ribonucleoprotein complex biogenesis, RNA processing, and RNA splicing. | – | (105) |
|
GSE62564 dataset: 493 NB patients, GSE12460 dataset: 47 NB patients |
SK-N-DZ, SK-N-SH, SK-N-BE(2)-C, SK-N-AS, SK-N-F1 | -/MYCN | – | MYCN amplification up-regulates SNHG1. | Poor OS and EFS | (106) | |
| GALNT8 | TCGA dataset: 88 NB cases | SK-N-AS, HEK293T | TCEA1, RBMX, MCM2, CBX3 | – | Suppressing the GAU1/GALNT8 cluster hinders tumor progression and growth. GAU1 recruits TCEA1 to activate GALNT8 expression. | Poor OS | (107) |
| GAU1 | |||||||
| MYCNOS-01 | 88 NB samples | KELLY, SY5Y | MYCN | – | MYCNOS-01 suppresses MYCN protein levels. The suppression of MYCNOS-01 or MYCN expression reduced cell proliferation and viability. | – | (108) |
| pancEts-1 | 42 NB patients and 88 NB cases from GSE16476 dataset | NB-1643, SK-N-BE(2), NB-1691, IMR32, BE(2)-C, (SK-N-AS, SH-SY5Y, SK-N-SH | hnRNPK, β-catenin | – | PancEts-1 increases the proliferation, invasion, and metastasis of NB cells. pancEts-1 binds to hnRNPK to enhances its interplay with β-catenin and stabilizes the β-catenin. | Poor survival | (109) |
| MALAT1 | 15 normal tissues, 19 primary NB, and 28 metastatic NB tissues | NGP, SH-SY5Y, NMB, SHEP21N, SKNAS, SHEP2, HEK293T |
Axl, AKT, ERK1/2 | – | MALAT1 overexpression increases invasion and migration. | – | (110) |
| – | BE(2)-C, HUVEC | FGF2 | – | MALAT1 significantly promotes cell migration, invasion, and vasculogenesis. | – | (111) | |
| – | BE(2)-C, CHP134 | -/N-Myc, JMJD1A | – | Migration and invasion rate increase following MALAT1 overexpression. | – | (112) | |
| GAS5 | – | IMR-32, CHLA-122, SMS-KAN, SK-N-Be(1), KCNA, NPE, SK-N-AS, LA-N-6, CHLA-15, SK-N-FI, CHLA-171, NB-EBc1, CHLA-42, GI-M-EN | p53, BRCA1, GADD45A, HDM2 | – | GAS5 loss results in defects in cell proliferation, apoptosis, but induces cell cycle arrest. | – | (113) |
| HCN3 | Tumor and para-tumor tissue samples (n = 6) | BE(2)-C | BID, Noxa, HIF-1α | – | Linc01105 knock-down increases HIF-1α and promotes cell proliferation. In contrast, linc01105 and HCN3 knock-down increase the apoptosis rate. | – | (114) |
| linc01105 | |||||||
| lncUSMycN | Versteeg dataset: 88 NB samples, Kocak dataset: 476 NB samples | BE(2)-C | NCYM, N-myc, NonO | – | LncUSMycN up-regulates NCYM expression. | – | (115) |
| 47 primary NB samples, Versteeg dataset: 88 NB tissues, Kocak dataset: 476 NB tissues | IMR32, BE2C, SK-N-DZ, CHP134, Kelly, SK-N-FI, SK-N-AS, NB69, SY5Y, SHEP, LAN-1 |
NonO, N-Myc | – | lncUSMycN increase up-regulates N-Myc RNA and NB cell proliferation. | Poor OS | (86) | |
| HOXD-AS1 | GSE3446 dataset: 102 NB patients | SH-SY5Y | MAGEA9B, SNN, TMEM86A, VIPR1, CREM, TSPAN2, CNR1, CREBL1, PTGS1, ADAMTS3, AMDMD2, ANG, ASNA1/retinoic acid | PI3K/Akt, JAK/STAT | Following RA treatment, HOXD-AS1 diminishes the expression of genes involved in NB progression, angiogenesis, and inflammation. | – | (116) |
| CAI2 | 62 primary NB samples and 25 healthy controls | FS15, NMB7 | P16, ARF | – | CAI2 expression is significantly higher in advanced-stage NB. | Poor OS | (87) |
| Paupar | – | N2A | KAP1, PAX6, RCOR3, PPAN, CHE-1, ERH | – | Paupar regulates expression of some target genes involved in the regulation of neuronal function and cell cycle. | – | (117) |
| – | N2A | PAX6, E2f2, E2f7, Cdc6, Cdkn2c, Kdm7a, Sox1, Sox2, Hoxa1, Hes1 | – | Paupar silencing disrupts the cell cycle transition and stimulates neuron differentiation. | – | (118) | |
| NORAD | 38 pairs of NB and normal tissues | SK-N-SH, IMR-32, HUVEC | MiR-144-3p, HDAC8 | – | NORAD enhances the proliferation, tumor growth, metastasis, and doxorubicin resistance, though it restricts apoptosis and autophagy. | – | (119) |
| CASC11 | 42 neonatal NB and 42 normal tissues | SK-N-AS and NB-1, hTERT-RPE1 | miR-676-3p, NOL4L, AGO2 | – | CASC11 depletion represses cell proliferation and invasiveness. | Poor survival | (120) |
| DUXAP8 | 45 NB patients, at 1 + 2+4S stage (n = 18) and 3 + 4 stage (n = 27) | SK-N-SH, IMR-32, HUVEC, HEK293T | miR-29, NOL4L | Wnt/β-catenin | DUXAP8 expression is positively related to the stage of NB tumors and is negatively associated with the survival rate of NB patients. DUXAP8 knock-down reduces the proliferation, colony formation, cycle, and motility of NB cells. | Lower OS | (121) |
| SNHG4 | 30 primary NB and ANTs | SH-SY5Y, CHP-212, SK-N-FI, IMR-32, HEK293T | miR-377-3p | – | LncRNA SNHG4 escalates NB proliferation, migration, EMT, and invasion and reduces the apoptosis rate. | Lower survival rate | (122) |
| lncNB | 476 NB patients | BMX | The super-enhancer driven long non-coding RNA lncNB promotes neuroblastoma tumorigenesis. | Poor prognosis | |||
| NHEG1 | GSE62564 dataset: 498 patients, 42 primary NB cases and 21 normal dorsal ganglia | MCF-10A, SK-N-BE(2), IMR32, BE(2)-C, NB-1643, NB-1691, SH-SY5Y, SK-N-SH, SK-N-AS, HCT116 |
DDX5, β-catenin/LEF1, TCF7L2 | Wnt/β-catenin | NHEG1 depletion accelerates differentiation and inhibits the proliferation and aggressiveness of NB cells. | Lower OS and EFS | (123) |
| XIST | 30 NB and ANTs | SK-N-BE(2), HEK293, GI-LI-N | HK2, miR-653-5p | – | XIST knock-down curtails tumorigenesis by suppressing proliferation and invasion. It also increases the radiosensitivity by diminishing colony constuction and glycolysis. | – | (124) |