# An Emerging Role of Long Noncoding RNAs as Novel Biomarkers for Breast Cancer Metastasis
## 5 Potential lncRNA-Based Biomarkers
### Other Potential lncRNA-Based Biomarkers Involved in the Metastatic Progression of Breast Cancer
NAMPT-AS promotes tumor progression by epigenetically regulating NAMPT and affecting the mTOR pathway [93]. The involvement of Colon Cancer-Associated Transcript 1 (CCAT1) and CCAT2 in the oncogenesis of TNBC has also been documented. CCAT1 promotes progression by downregulating miR-218 and upregulating Zinc Finger Protein X (ZFX) and serves as an independent predictor of decreased OS and PFS, while CCAT2 upregulates OCT4-PG1 and activates the Notch2 signaling pathway through inhibition of miR-205 [94; 95; 96]. RP1-5065, a novel lncRNA, is highly expressed in BC and is associated with poor prognosis, promoting tumor proliferation and metastasis by repressing p27 kip1 protein expression and maintaining the EMT and stemness states in cancer cells both in vivo and in vitro [97]. Based on the analysis of 56 BC specimens, another lncRNA, BCHE, was found to have a strong correlation with LNM [98]. Expression of Neuroblastoma-associated transcript 1 (NBAT1), which is downregulated in BC, correlates with LNM and unfavorable patient prognosis. Mechanistically, NBAT1 interacts with the PRC2 complex member EZH2 to modulate gene expression, specifically affecting the WNT signaling pathway inhibitor DKK1 [99]. Another lncRNA downregulated in BC tissues is Taurine-upregulated gene 1 (TUG1), which is downregulated in BC tissues, with its reduced levels strongly correlating LNM with the presence of the tumor suppressor p53 [100]. Ezrin Antisense RNA 1 (EZR-AS1) is upregulated in BC and acts as an oncogene by activating the Wnt/\(\beta\)-catenin signaling pathway, which is involved in regulating cell proliferation and survival [101]. In addition, Progression-Associated lncRNA in Breast Cancer (PRLB) remains a biomarker of metastatic range and shorter survival rate [102]. It is worth mentioning that the knockdown of Breast Cancer Anti-Estrogen Resistance 4 (BCAR4) resulted in a reduction in LNM in the lungs of mice models. BCAR4 enhances BC metastasis by interacting with SNIP1 (Smad Nuclear Interacting Protein 1) and PNUTS (Phosphatase Nuclear Targeting Subunit) in response to CCL21 (Chemokine C-C Motif Ligand 21). This interaction activates the noncanonical Hedgehog/GL2 signaling pathway, promoting cell migration [103]. Last, but not least, the lncRNA Highly Upregulated in Liver Cancer (HULC) is found to be overexpressed in BC, correlating with increased malignancy and metastasis. HULC promotes tumor progression by directly binding to miR-6754-5p, which regulates the expression of LYPD1 [104]. [PERSON] et al. proved that HULC promoted metastasis both in vivo and in vitro. Furthermore, HULC acted as a crucial regulator of the IGF1R signaling pathway in BC by directly binding to IGF1R's intragenic regulatory elements, enhancing its expression and activation of the PI3K/AKT pathway [105]. To provide a comprehensive overview of the key findings related to lncRNAs as potential biomarkers for BC metastasis, Table 1 summarizes the most relevant studies in this area.