The HOXC8 gene is 3658 nucleotide long and consists of two exons. There are 112 known SNPs in HOXC8 gene and most of them locate on the 5 end of the gene.

The transcribed matured mRNA is 2290 nucleotide in length.
Transcription regulators: 1) CDX1, which is a member of the caudal-related homeobox transcription factor gene family, activates HOXC8 transcription by binding to its early enhancer (Schyr et al., 2012). 2) Activating protein 2 delta (AP2δ) transcription factor, which is one of AP2 five family members (AP2α, AP2β, AP2γ, AP2δ and AP2ε), recruits Ash2I and ALR to the HOXC8 locus, resulting in H3K4me3-mediated gene activation (Tan et al., 2008). 3) Menin, which is a tumor suppressor gene associated with a syndrome known as multiple endocrine neoplasia type 1, binds to HOXC8 locus by associating with a histone methyltransferase complex containing two trithorax family proteins, MLL2 and Ash2L (MacConaill et al., 2006). 4) GTF2IRD1, which is a TFII-I family of transcription factors, interacts with HOXC8 early enhancer and represses the gene transcription (Thompson et al., 2007).

HOXC8 protein contains 242 amino acids and is 27755 Da. HOXC8 contains a ~60 amino acid homeodomain with helix-turn-helix (HTH) motif which functions as a DNA binding domain. HOXC8 binds to DNA as monomers or homo- and/or heterodimers in a sequence-specific manner.

In mouse embryogenesis: HOXC8 is expressed in the neural tube and somatic mesoderm as well as in the prospective thorax. During embryogenesis, Hoxc8 is initially expressed with the identical boundaries in the mesoderm and neurectoderm. Subsequently, Hoxc8 expression creeps forward and the boundaries in mesoderm and neural tube diverge. The gene is also expressed in both the neural tube and the somites in the prospective thorax (Pollock et al., 1992; Shashikant and Ruddle, 1996).
Cancers: Elevated HOXC8 expression is detected in breast cancer (Li et al., 2014; Li et al., 2010), cervical cancer (Alami et al., 1999), prostate cancer (Waltregny et al., 2002), esophageal cancer (Du et al., 2014), pancreatic cancer (Adwan et al., 2011).
Organs: HOXC8 is expressed in hematopoietic organs, brain, breast, placenta, liver, bone marrow, kidney, intestine and nervous systems, etc.
Cell types: HOXC8 is expressed on a variety of cell types, including fibroblasts, neurons, hair, adipose, skeletal and smooth muscle cells, lymph T cells, endothelial and epithelial cells, mesenchymal and stem cells, etc.
Translation regulation: Members of microRNA 196 family (miR-196a1, miR-196a2 and miR-196b) can bind to the 3-UTR of HOXC8 mRNA, leading to the repression of HOXC8 translation (Li et al., 2010).

Nucleus.

HOXC8 serves as a transcription factor to regulate the expression of genes that are implicated in skeletal and neural development in embryogenesis and cancer progression.
Embryogenesis: Like other HOX proteins, HOXC8 plays an essential role in embryo anterior-posterior patterning and is responsible for skeletal and neural development (Juan et al., 2006; Thickett and Morgan, 2002). Null mutants of HOXC8 show neuromuscular defects in the forelimb and skeletal defects in the ribs and vertebrae of the thorax (Le Mouellic et al., 1992). Overexpression of a Hoxc8 transgene has been shown to cause cartilage defects by inhibiting the maturation and stimulating the proliferation of chondrocytes (Yueh et al., 1998).
Transcriptional regulation: As a transcription factor, microarray data indicate that HOXC8 regulates the expression of genes that are involved in cell proliferation, migration, adhesion, and differentiation (Lei et al., 2005). In response to bone morphogenetic protein (BMP) stimulation, HOXC8 activates the transcription of osteopontin (OPN) by interacting with Smad1 (Shi et al., 1999). In breast cancer cells, HOXC8 functions as a transcription factor to regulate cadherin 11 (Cdh11) transcription (Li et al., 2014; Li et al., 2011). ChIP assays demonstrate that HOXC8 can bind to the promoter of target genes including NCAM (neural cell adhesion molecule), PEDF (pigment epithelium-derived factor), ZAC1 (the zinc finger protein regulator of apoptosis) and PCNA (proliferating cell nuclear antigen) (Lei et al., 2006; Min et al., 2010). In addition, HOXC8 has also been identified as a transcription repressor. For instance, HOXC8 can downregulate the expression of Mgl1 and Smad6 by directly binding to the promoter regions of these 2 genes (Kang et al., 2010; Ruthala et al., 2011).
Stem cells: HOXC8 is expressed in vascular wall-resident multi-potent stem cells (VW-MPSCs), and silencing its expression significantly reduces cell sprouting capacity and increases expression of the smooth muscle cells marker genes (Klein et al., 2013).
Cancers: HOXC8 plays an essential role in cancer development, including breast, prostate, cervical and pancreatic cancers by facilitating cell migration and invasion (Adwan et al., 2011; Alami et al., 1999; Axlund et al., 2010; Du et al., 2014; Li et al., 2010).