HOX and MEINOX in cellular plasticity, fibrosis, and cancer

Table 2 The effects of protein-coding HOX genes in various fibrotic diseases

HOX genes	Disease	Mode of function in fibrosis	Proof of concept or mechanism of action	Ref.
HOXA2	Liver fibrosis	Anti-fibrotic	Gene silencing of HOXA2 via DNA hypermethylation correlates with advanced fibrosis in chronic hepatitis B	[198]
	Lung fibrosis	Pro-fibrotic	Expression is significantly upregulated in mesenchymal stromal cells from patients with progressive idiopathic pulmonary fibrosis	[199]
HOXA5	Lung fibrosis	Pro-fibrotic	HOXA5 drives DNM3OS transcription, which recruits EZH2 to suppress TSC2, promoting fibroblast proliferation, migration, and ECM gene expression	[169]
HOXA9	Skin fibrosis	Anti-fibrotic	In keloids, overexpression of HOXA9 reduces cell migration, increases MMP3 expression, regulates Wnt pathway inhibitors (reducing PRICKLE1, increasing DKK1 expression)	[79]
HOXB7	Lung fibrosis	Pro-fibrotic	Found to be upregulated in IPF patients’ lung tissues	[175]
HOXB13	Liver fibrosis	Pro-fibrotic	The number of HOXB13+ cells in fibrotic liver increases. HOXB13 expression is correlated with increased hepatic inflammatory activity, but not with fibrosis stages	[165]
HOXC8	Liver fibrosis	Pro-fibrotic	Inhibition of HOXC8 suppressed the hepatic stellate cell activation and the expression of fibrosis-associated genes (α-SMA and COL1A1)	[187]
HOXD10	Kidney fibrosis	Anti-fibrotic	In a mouse kidney fibrosis model, HOXD10 overexpression significantly reduced collagen deposition and renal dysfunction	[200]

DNM3OS: Dynamin 3 opposite strand; EZH2: Enhancer of zeste homolog 2; TSC2: Tuberous sclerosis complex subunit 2; ECM: Extracellular matrix; MMP: Matrix metalloproteinase; DKK1: Dickkopf-1; IPF: Idiopathic pulmonary fibrosis; α-SMA: Alpha-smooth muscle actin; COL1A1: Collagen type 1.