Table 1 Molecular mechanisms by which H19 regulates apoptosis in multiple tumors.
From: Long noncoding RNA H19: functions and mechanisms in regulating programmed cell death in cancer
PCD type | Tumor types | H19 expression | Signaling pathway | Molecular Mechanisms | Cell processes | References |
|---|---|---|---|---|---|---|
Apoptosis | Acute myeloid leukemia (AML) | Up regulation | Wnt/β-catenin | ↑ID2; ↓miR-29a-3p, ↑β-catenin, ↑T-cell factor (TCF), ↑lymphoid enhancer factor 1 (LEF1) | Promote proliferation, migration and invasion; Inhibit apoptosis | |
Apoptosis | Breast cancer (BC) | Up regulation | Akt; Wnt/β-catenin | ↑Bax, ↑cleaved caspase-3; ↓p-Akt (Ser473), ↓Bcl-2 ↓BIK; ↓MiR-138, ↑SOX4 | Promote proliferation, progression and EMT; Facilitate drug resistance; Suppress apoptosis | |
H19/miR-340-3p | competitively binding miR-340-3p, regulating tyrosine 3-monooxygenase/tryptophan 5-monooxygenase acti-vation protein zeta (YWHAZ) and potentiate the Wnt/β-catenin signaling | |||||
Apoptosis | Cutaneous squamous cell carcinoma (CSCC) | Up regulation | H19/microRNA‑675 axis | ↑miR-675, ↓p53 | Promote EMT, proliferation, invasion | [69] |
Apoptosis | Esophageal cancer (EC) | Up regulation | let-7c/STAT3/EZH2/β-catenin axis. | ↑STAT3, ↑EZH2, ↑β-catenin | Promote EMT, metastasis, migration, and invasion | [70] |
Apoptosis | Gastric cancer (GC) | Up regulation | miR-138/E2F2 axis | ↓p53; ↓let-7a; ↓miR-138, ↑E2F2 | Increase proliferation; Inhibit apoptosis | |
Apoptosis | Glioma | Up regulation | Wnt/β-catenin; Negative feedback loop of H19/miR‐675/VDR | ↑CREB1; ↑DVL2,↑cyclinD1, ↑β-catenin； ↓miR-152； ↓protein level of vitamin D receptor (VDR); ↓miR-140, ↑inhibitor of apoptosis-stimulating protein of p53 (iASPP) | Prompt invasion, proliferation, radio-resistance; Inhibit apoptosis | |
Apoptosis | Hepatoblastoma | Up regulation | miR-675/FADD, miR‐138/PTK2; | ↑:H19, miR‐675, PTK2, HIFIA, FAK (HBV +), ↓: miR-138, FADD, caspase‐8, caspase‐3(HBV+); | Promote metastasis, progression | [59] |
Apoptosis | Hepatocellular carcinoma (HCC) | Up regulation | MAPK/ERK; miR-520a-3p/LIMK1 axis; miR-15b/CDC42/PAK1 axis; EMT | ↑Protein levels of MAPK and ERK; ↓p53; ↓miR-520a-3p, ↑LIMK1; ↑CDC42, ↓ miR-15b; ↓ EMT pathway-related genes (N-cad-herin, Vimentin, β-catenin, MMP-9) | Suppress oxidative stress (OS); Reverse chemotherapy resistance of CD133þ cancer stem cells; Inhibit apoptosis; Promote EMT, proliferation, migration, invasion | |
Apoptosis | Lung cancer | Up regulation | H19/miR-29b-3p/STAT3 | ↓miR-29b-3p; ↓EMT-specific proteins: vimentin, Snail, Slug (↑epithelial cadherin); ↑miR‐675‐5p, ↓p53, ↓Bax, ↑ Bcl‐2 | Promote proliferation, EMT; Decrease the survival rate and viability | |
Apoptosis | Multiple myeloma (MM) | Up regulation | H19/miR-29b-3p/MCL-1 | ↓ miR-29b-3p, ↑MCL-1 Transcriptional translation | Reduce cell sensitivity to the chemotherapeutic drug BTZ; Inhibit apoptosis | [39] |
Apoptosis | Nephroblastoma | Down regulation | miR-675/TGFBI axis | ↓H19, miR-675; ↑TGFBI | Inhibits proliferation; Enhance apoptosis; Induce growth inhibition and morphological changes | [66] |
Apoptosis | Ovarian cancer (OC) | Up regulation | H19 → EZH2 → p21/PTEN; PI3K/AKT/mTOR | ↑p21 and PTEN protein levels; ↓ EZH2 protein; ↓serum miR-140- 5p, ↓ p-PTEN, ↑ p-AKT (Thr308), p-AKT (Ser473), p-mTOR (Ser2448), p-FoxO1 (Ser256), p-MDM2 (Ser166), p-NF-κB p65 (Ser536), and p-GSK-3β (Ser9) | Suppress apoptosis, cell mortality, drug sensitivity; Promote invasion, Migration, EMT |
