**3.1 Epigenetics in bone metastasis**

Bone is one of the most common sites of metastasis for a variety of solid tumors, including lung, liver, breast, and prostate, with bone metastases being seen in 70% of metastatic prostate and breast cancer patients [92]. Unfortunately, once cancer has progressed to the bone, it is seldom treated and is associated with countless complications such as discomfort, increased fracture risk, and hypercalcemia. This finding has prompted scientists interested in bone and cancer biology to investigate the bone, revealing a number of mechanisms, including epigenetically related elements that promote cancer spread to the bone (**Table 1**).



*Notes: ncRNA: non-coding RNA; TP53INP1: tumor protein 53-induced nuclear protein 1; NKX2-1: NKX homeobox-1, EGFR: epidermal growth factor receptor, PI3K: phosphoinositide-3-kinase; TRIM-44: tripartite motif-44; PHB2: Prohibitin 2; TGF-β: transforming growth factor β; MPAK: mitogen-activated protein kinase; OPG: osteoprotegerin; ROR1: receptor tyrosine kinase (RTKs)-like orphan receptor-1; YAP: yes-associated protein; TRAF-3: TNF receptor-associated factor-3; COL1A1: collagen type I alpha 1 chain; PTGS2: prostaglandin-endoperoxide synthase 2; HIF1A: hypoxiainducible factor 1 alpha subunit; CrkL: v-crk avian sarcoma virus CT10 oncogene homolog-like; PDCD4: programmed cell death 4; IBSP: integrin-binding sialoprotein; RUNX2: runt-related transcription factor 2; SFPQ: splicing factor proline- and glutamine-rich; and PTBP2: polypyrimidine tract-binding protein 2.*

#### **Table 1.**

*Epigenetic biomarkers in bone metastases of various cancers.*
