Table 1.
Targets identified for HOX factors in human cancer.
| HOX protein | Role | Interference | Cancer type | Year | Reference |
|---|---|---|---|---|---|
| HOXA1 | Oncogene | Sequester G9a/EZH2/Dnmts, sponge miR-193a-5p, via cyclin D1, via miR-100 | Breast cancer, glioma, GC, lung cancer | 2014,2016,2018 | (38, 63, 97, 116) |
| HOXA3 | Oncogene | Upregulate methylation level, promote differentiation to angiogenesis, confer cisplatin resistance | NSCLC, PTC, blood | 2011,2019 | (13, 117, 118) |
| HOXA4 | Tumor suppressor | Downregulate β-catenin, Cyclin D1, c-Myc and survivin, indicate inhibition of Wnt signaling, upregulate GSK3β | Lung cancer, ovarian carcinoma | 2009,2018 | (14, 74, 79) |
| HOXA5 | Tumor suppressor | Induce apoptosis mechanism mediated by cas2 and cas8; regulate E-cadherin and CD24; methylate promoter region & limit p53 expression | Breast cancer, mammary cancer, cervical cancer | 2015-2021 | (9, 21, 39–41, 50, 51, 80, 84, 119–126) |
| HOXA6 | Oncogene | Coexpress with PBX2 | GC, CRC, leukemia | 2021 | (55) |
| HOXA7 | Oncogene | Combine to Snail promoter, cyclin E1/CDK2, activate Snail | Cervical cancer, HCC | 2016,2020 | (25, 81) |
| HOXA9 | Oncogene | Pioneer factor at de novo enhancers and recruit CEBPα & MLL3/MLL4 complex, regulate BRCA1, activate JAK/STAT, induce 1GF1R expression | Pancreatic cancer, leukemia, NSCLC | 2017-2020 | (75, 77, 86–90, 92, 94, 127–132) |
| HOXA10 | Oncogene | Suppress FASN transcription by forming a protein complex with AR and prevent AR recruitment to FASN gene promoter, hinder mir195 | Prostate cancer, testicular cancer, HNSCC | 2020 | (35) |
| HOXA11 | Oncogene | LncRNA HOXA11-AS recruit EZH2 along with the histone demethylase LSD1 or DNMT1 | GC, LUAD, renal cancer | 2016,2017,2018 | (56, 57) |
| HOXA13 | Oncogene | IGF-1 | CRC, GC | 2021 | (133) |
| HOXB4 | Tumor suppressor | Downregulate activity of Wnt/β-catenin signaling pathway, downregulate P-gp, MRP1 and BCRP expression | Cervical cancer, leukemia | 2016,2021 | (82, 91) |
| HOXB5 | Oncogene | Transactivate CXCR4, ITGB3, FGFR4, CXCL1 | HCC, CRC, breast cancer, HNSCC, GC | 2015,2021 | (26, 42, 134) |
| HOXB7 | Oncogene | Reprogram to iPSC with comparable efficiency to LIN28B or c-MYC, activate TGFβ signaling pathway | Lung cancer, GC | 2016,2018 | (15, 27, 34, 58, 135, 136) |
| HOXB8 | Oncogene | Instigate BACH1-mediated transcriptional cascade, viaZEB2 targets | GC, CRC | 2017,2020 | (59, 137) |
| HOXB13 | Tumor suppressor | Suppress C-Myc expression to exert antitumor effects via β-catenin/TCF4 signals, network with ABCG1/EZH2/Slug | Colon cancer, lung cancer, prostate cancer | 2015-2019 | (16, 43–46, 60, 65–68, 138–141) |
| HOXC6 | Prognosis marker, oncogene | Enhance BCL2-mediated antiapoptotic effects, drive MET | Prostate cancer, cervical cancer,HCC | 2019 | (28, 69, 83) |
| HOXC8 | Oncogene | Upregulate TGFβ1, repress LMP1 | NSCLC, TNBC | 2018 | (17, 47, 48, 142, 143) |
| HOXC9 | Oncogene | Mediate autophagy, via mir-495/HOXC9 axis, promote multi-chemoresistance | Bladder cancer, neuroblastoma, NSCLC | 2011,2015,2016 | (4, 5, 32) |
| HOXC10 | Oncogene | Via upregulating PDPK1, VASP, EMT, promote angiogenesis, induce immunosuppressive gene | HCC, lung cancer, ovarian cancer | 2014-2020 | (6, 7, 19, 29, 49, 61, 144, 145) |
| HOXC13 | Oncogene | Modulate CCND1 & CCNE1 | Lung adenocarcinoma | 2017 | (20) |
| HOXD3 | Tumor suppressor | Inhibit HDAC1 via ITGA2 pathway & MAPK/AKT signaling | HCC, CRC | 2019,2020 | (146, 147) |
| HOXD8 | Oncogene | Enhance LINC01116 contribution to progression of BCa via targeting ELK3 & HOXD8 | Bladder cancer | 2020 | (33) |
| HOXD9 | Oncogene | Transactivate RUFY3 & ZEB1, promote MET | GC, HCC | 2015,2019 | (30, 62) |
| HOXD10 | Tumor suppressor | Inhibit RHOC/AKT/MAPK pathway, upregulate mir-10b | CRC | 2019 | (76, 148) |
| HOXD13 | Tumor suppressor | Inhibit SMAD1, suppress BMP4 | Prostate cancer | 2021 | (70) |