Table 2.
Therapeutic values of HOX factors in human cancer.
| Gene | Down regulation effects | Downstream regulated molecules or pathways | Upstream regulatory molecules | Tumor x cell lines x normal tissues | Related targeting molecules | Intervention therapy | Clinical trial number & Reference |
|---|---|---|---|---|---|---|---|
| HOXA1 | Proliferation, migration, invasion, metastasis | Wiping out epigenetic silencing of HOXA1 | HOTAIRM, G9a, EZH2 | GBM | Histone modification of H3K9, H3K27 | / | (116) |
| HOXA1 | Metastasis, invasion | MITF | TGF-β | Melanoma | TGF-β signaling | / | (97) |
| HOXA1 | Chemoresistance(up) | / | MiR-100 | SCLC | HOXA1 | / | (22) |
| HOXA3 | Occurrence, development | / | HOXA-AS2, miR-15a-5p | PTCC | HOXA-AS2/miR-15a-5p/HOXA3 axis | / | (118) |
| HOXA3 | Chemoresistance | EMT& Cisplatin resistance | HOXA-A3 | NSCLC | HOXA-A3 | / | (13) |
| HOXA4 | Growth, migration, invasion | β-catenin, cyclin D1, c-Myc, survivin | GSK3β | Lung cancer | GSK3β | LiCI | (14) |
| HOXA5 | Angiogenesis | / | MiR-130-3p | HCC | SP1/MiR-130-3p/HOXA5 | SP1 inhibitor | (22) |
| HOXA5 | Growth, migration, invasion | CAF | Exosomal miR-181d-5p | Breast cancer | HOXA5/CDX2 | / | (41) |
| HOXA5 | Arresting cell cycle | TP53, P21 | Binding to TAAT motif within promoter of TP53 | Cervical cancer | Wnt/β-catenin | / | (84) |
| HOXA7 | Migration, invasion | Snail | / | HCC | HOXA7/Snail | / | (25) |
| HOXA7 | Proliferation, invasion | / | CircSLC26A4 | Cervical cancer | QKI/circSLC26A4/miR-1287-5p/HOXA7 axis | / | (81) |
| HOXA9 | Leukemogenesis | STAT5, AP1 | JAK3/STAT5 | Leukemia | Mutant JAK/STAT/HOXA9 | PIM1 kinase | (88) |
| HOXA9 | Leukemogenesis | CEBPα, MLL3, MLL4 | HOXA9/Meis | Leukemia | Histone H3K4 methylation | / | (128) |
| HOXA9 | Leukemogenesis | Meis, Syk | MiR-146a | Leukemia | HOXA9/Meis/Syk feedback loop | / | (87) |
| HOXA9 | Leukemogenesis | Erg | Trib1 | Leukemia | HOXA9/Trib1/Erg | JQ1 | (90) |
| HOXA9 | Regulating glucose metabolism reengineering | HIF1α, HK2, GLUT1, PDK1 | Onco-miR-365 | CSCC | MiR-365-HOXA9-HIF1α axis | / | (127) |
| HOXA9 | Tumor aggression | HOXA9 | BRCA1 | Breast cancer | / | / | (132) |
| HOXA10 | Tumor aggression | HOXA10, CCSCs | LINC00355/miR-195 | HNSCC | LINC00355 | / | (35) |
| HOXA11 | Proliferation, cell-cell adhesion pathway | LncRNA HOXA11-AS, LSD1 | EZH2 | GC | EZH2/HOXA11-AS/LSD, HOXA11-AS/miR1297/EZH2 | / | (56) |
| HOXA11 | Metastasis, invasion | β-catenin, P21, KLF2 | WDR5/EZH2/STAU1 | GC | HOXA11-AS | / | (57) |
| HOXA13 | Metastasis | ACLY, IGF1R | IGF1 | CRC | IGF1R/ACLY | Linsitinib/ETC-1002 | (133, NCT01154335, NCT01016860) |
| HOXB3 | Tumor aggression | RASSFIA, DNMT3B | POL2 | Lung adenocarcinoma | RASSFIA | RASSFIA epigenetic silencing | (153) |
| HOXB3 | Tumor aggression | CDCA3 | / | Primary prostate cancer/PC-3/LNCaP | HOXB3 | / | (72) |
| HOXB4 | Arresting cell cycle | β-catenin, TCF, c-Myc | / | Cervical cancer | Wnt/β-catenin | / | (82) |
| HOXB5 | Metastasis | ITGB3, CXCR4 | CXCL12 | CRC | CXCR4 | AMD3100 | (134, NCT02179970) |
| HOXB5 | Metastasis | CXCL1, FGFR4 | FGF19 | HCC | FGFR4 | BLU-554 | (26, NCT02508467, CT04194801) |
| HOXB7 | Metastasis | TGFβ2, SMADS | / | Breast cancer | MET | / | (135) |
| HOXB7 | Metastasis | c-Myc, Slug | / | HCC | MET | / | (27) |
| HOXB8 | Invasiveness | BACH1 | / | CRC | / | / | (137) |
| HOXB9 | Angiogenesis | IL-6, VEGF | / | Colorectal cancer | VEGF | Bevacizumab | (166) |
| HOXB9 | Migration, tumor growth | JMJD6 | Ack27 | Lung adenocarcinoma | Ack27-HOXB9 | / | (23) |
| HOXB9 | Migration, tumor growth | EZH2 | Ack27-HOXB9 | Clone cancer | Ratio of Ack27-HOXB9/HOXB9 | / | (167) |
| HOXB13 | Tumor aggression | / | / | Prostate cancer | HOXB13, G84E variant | / | (71) |
| HOXB13 | Metastasis | RFX6 | Rs339331 at 6q22 | Prostate cancer | RFX6 | / | (68) |
| HOXB13 | Tamoxifen resistance of breast cancer | IL-6 | HBXIP | Breast cancer | HBXIP | Aspirin | (45) |
| HOXB13 | Tumor aggression | β-catenin, TCF4, c-Myc | DNMT3B | RCC | DNMT3B-HOXB13-c-Myc axis | / | (141) |
| HOXC8 | Cisplatin chemoresistance, anti-apoptosis | TGFβ1 | / | NSCLC | HOXC8 | / | (17) |
| HOXC9 | Proliferation, migration | DAPK1-beclin1 | / | Glioblastoma | HOXC9/autophagy | / | (4) |
| HOXC9 | Chemoresistance | SRSF2, PLAU, HIC2 | MiR-193a-3p | Bladder cancer | MiR-193a-3p/HOXC9/DNA damage | / | (32) |
| HOXC10 | Aberrant expression | HOXC10 | PRC2 | NSCLC | Kras-mutant/HOXC10 | BET/MEK inhibitor | (18) |
| HOXC10 | Angiogenesis | VEGFA | / | Gliomas | HOXC10/VEGFA | Bevacizumab | (7) |
| HOXC10 | Invasiveness | VASP, PDPK1 | IL1β | HCC | IL1R1 | Anakinra | (29) |
| HOXD3 | Tumor aggression | Integrinβ3 | HOXD-AS1 | CRC | HOXD-AS1-HOXD3-integrinβ3 | / | (147) |
| HOXD10 | Invasion | Snail, Slug, MMP2, MMP9, MMP14, E-cadherin | MiR-23a | Gliblastoma | MiR-23a/HOXD10 | / | (148) |