**3.4 Epigenetics in brain metastasis**

Through activation of EMT- and MSN-mediated up-regulation of c-Met, the loss of lncRNA XIST increases breast cancer brain metastasis by boosting both stemness and aggressiveness of tumor cells [129] (**Table 2**). Yoo et al. proved the therapeutics function of miRNA-10b by targeting the brain metastases process in breast cancer [130]. JAK2-binding lncRNA BCBM promotes breast cancer brain metastasis by regulating STAT3 [132]. circBCBM1 is involved in breast cancer brain metastasis via circBCBM1/miR-125a/BRD4 axis [133]. By modulating connexin 43 expression, dysregulation of lncRNA-CCRR contributes to breast cancer brain metastases through intercellular coupling [134]. Loss of miRNA let-7d and active hypoxia- inducible factor-1 (HIF1) signaling enhances breast cancer brain metastasis via platelet-derived growth factor (PDGF), while pharmacologic inhibition of PDGF receptor (PDGFR) inhibits brain metastasis, implying new therapeutic possibilities [135]. miR-132-3p, miR-199a-5p, miR-150-5p, miR-155-5p, miR-802-5p and miR-194-5p from breast cancer cells also were identified the important role in brain metastasis [136, 137].

In triple-negative breast cancer, miR-211 regulates brain metastatic selectivity via the SOX11/NGN2 axis [138].
