Table 2.
Up-regulated miRNAs in neuroblastoma (NB, neuroblastoma; OS, overall survival).
| miRNA | Number of clinical samples | Assessed cell line | Targets/regulators | Signaling pathway | Function | Effect of miRNA up-regulation on patients’ prognosis | Ref |
|---|---|---|---|---|---|---|---|
| miR-25 | Versteeg dataset: 88 samples, Kocak dataset: 649 samples, SEQC dataset: 498 samples | SH-SY5Y | Gsk3β/SLC34A2 | Wnt | SLC34A2 inhibits the stemness of NB cells via the miR-25–Gsk3β axis. | – | (71) |
| miR-640, miR‐543, miR‐624‐3p, miR‐196‐b | 50 NB tissues | SH-SY5Y, SK‐N‐AS, NGP, SK‐N‐BE2 | ING5 | – | Suberoylanilide hydroxamic acid downregulates these miRNAs to induce ING5 overexpression. | – | (69) |
| miR-3613−3p | – | BE(2)-C, Kelly, IMR−32, SK−N−SH, CHP−134, LAN−1, LAN−5, PC3 | APAF1, DICER, DFFB, VHL, NF1/MCPIP1 | Wnt, TGFβ, Akt | The up-regulation of miR-3613-3p increases viability but reduces the apoptosis of NB cells. | – | (72) |
| miR-181a/b | 32 primary NB tissues and 6 gangliocytoma tissues as controls | SK-SY5Y, SK-N-SH, BE(2) C, IMR-32, HUVEC, HEK293T | ABI1 | – | High miR-181a/b expression markedly enhances the proliferation, tumorigenesis, progression, migration, and invasion of NB cells, though it reduces the apoptosis rate. MYCN amplification and miR-181a expression are correlated. | – | (73) |
| – | SH-SY5Y | p38MAPK/triptolide | NF-κB | Through down-regulating miR-181a/b level, Triptolide inhibits cell viability, proliferation, and migration, but induces cell apoptosis. | – | (74) | |
| miR-181a | – | SH-SY5Y, A172, U251 | PARK2 | – | miR-181a suppresses mitochondrial uncoupling agents-induced mitophagy by decreasing the destruction of mitochondrial proteins. | – | (75) |
| miR-221 | 31 NB tissues | SK-N-AS, SK-N-DZ, IMR-32, HEK293T, SH-SY5Y | LEF1, NLK, p21, p27, p57 | Wnt | miR-221 diminishes LEF1 phosphorylation but up-regulates MYCN. Overexpression of miR-221 enhances the cell cycle transition especially in S-phase, promoting the proliferation of NB cells. | Poor survival rate | (76) |
| miR-558 | 30 primary NB and 10 ganglioneuroblastoma samples, GSE62564 database: 498 NB cases | NB-1643, SK-N-BE(2), NB-1691, IMR32, BE(2)-C, SK-N-AS, SH-SY5Y, SK-N-SH, HUVEC | AGO2, HIF-2α | – | miR-558 enhances the proliferation, invasion, metastatic capacities, and angiogenic potential. | Poor OS | (77) |
| 30 primary NB cases | SK-N-SH, SK-N-AS, SH-SY5Y, SK-N-BE(2), HUVEC | HPSE, VEGF, AGO1 | – | Knock-down of endogenous miR-558 reduced the proliferation, invasion, metastasis, and angiogenic potential. | – | (78) | |
| miR-1303 | 8 NB and adjacent normal nerve tissues | U343, SK-N-SH, SH-SY5Y, LAN5, IMR-32, SH-EP | GSK3β, SFRP1, p21, p27, MYC, CyclinD1 | – | miR-1303 overexpression results in up-regulated proliferation rates. | – | (70) |
| miR-19b | – | SH-SY5Y, BE(2)-M17 | p-AKT, PTEN | mTOR | AZD8055 significantly reduces miR-19b and p-AKT expression and enhances the cytotoxic activity of mTOR inhibitors and PTEN levels. miR-19b overexpression reverses mTOR inhibitors toxicity and cell viability. | – | (79) |
| miR-21 | CHL1 | miR-21 promotes the proliferation and invasion of NB cells. | (80) |