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Table 2 Action mechanisms of HOX proteins in gastric cancer

From: Homeobox proteins are potential biomarkers and therapeutic targets in gastric cancer: a systematic review and meta-analysis

HOX proteins Expression Upstream Downstream Pathways Reference
HOXB9 Downregulated NA NA ↓cells proliferation, migration and invasion; ↑MET; AKT and NF-κB pathway [15, 34, 35]
HOXD10 Downregulated miR-10b, miR-92b-3p IGFBP3 ↓cells proliferation, migration and invasion; AKT pathway; RhoC pathway [16, 36,37,38,39]
HOXA5 Downregulated miR-196a NA ↓cells G1-S transition, proliferation and colony formation; ↓angiogenesis [17, 18]
HOXA10 Upregulated NA miR-196b-5p, BCL2 ↑cells viability, proliferation, colony information, migration and invasion ↓apoptosis; ↑tumor metastasis; JAK1/STAT3 signaling; HOXA10/miR-196b-5p axis;
↓cells growth, motility and invasive activity;
[19,20,21, 40,41,42]
HOXA13 Upregulated lncRNA HOTTIP DHRS2, cadherin17 ↑cells proliferation, migration and invasion; ↑EMT; TGF-β pathway, ERK1/2 pathway, Wnt/β-catenin pathway, MDM2-p53-MRP1 pathway; chemotherapy resistance to 5-FU [22, 23, 43,44,45,46]
HOXC6 Upregulated lncRNA HOTAIR NA ↑cells proliferation, colony formation, migration and invasion; ERK signaling; [24, 47, 48]
HOXB7 Upregulated NA NA ↑cells G1-S transition, proliferation, migration and invasion; ↑EMT; ↓apoptosis; AKT/MAPK pathway; Src-FAK pathway; PIK3R3/ AKT pathway [25, 26, 49, 50]
HOXA1 Upregulated NA NA ↑cells proliferation, invasion and migration; ↑cyclin D1 [27]
HOXA9 Upregulated miR-182 NA ↑cells proliferation, migration and invasion; ↑tumor progression [28, 51]
HOXC9 Upregulated miR-26a NA ↑EMT and stem cell-like phenotypic acquisition; ↑tumor metastasis [29]
HOXC10 Upregulated miR-136 CST1 ↑cells migration and invasion; ↑tumor growth and peritoneal metastasis; ATM/NF-kB pathway; MAPK signaling [30, 52,53,54,55]
HOXD4 Upregulated NA NA ↑cells proliferation, migration and invasion; ↑c-Myc and cyclinD1 [31]
HOXA11 Controversial STAT3 STAT3 Wnt pathway [32, 56, 57]
HOXD9 Upregulated NA RUFY3 ↑cells proliferation, invasion and migration; ↑tumorigenesis and metastasis [33]
  1. ↓: inhibit; ↑: promote; NA Not available, AKT Protein kinase B, ATM Ataxia telangiectasia mutated, BCL2 B cell lymphoma-2, CST1 Cystatin 1, DHRS2 Dehydrogenase/reductase 2, ERK Extracellular regulated protein kinases, FAK Focal adhesion kinase, IGFBP3 Insulin-like growth factor binding protein-3, JAK1 Janus kinase 1, MAPK Mitogen-activated protein kinase, MDM2 Murine double minute 2, MET Mesenchymal epithelial transition, MRP1 Multidrug resistance-associated protein 1, PIK3R3 Phosphoinositide-3-kinase, regulatory subunit 3, RhoC Ras superfamily of GTP-binding protein, Src Steroid receptor coactivator, RUFY3 RUN and FYVE domain containing 3, 5-FU 5-fluorouracil