# 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  
In addition to the aforementioned lncRNAs, several other lncRNAs have been identified as potential biomarkers that may play significant roles in the metastatic progression of BC. These emerging lncRNAs add further complexity to our understanding of BC metastasis and highlight the diverse mechanisms through which lncRNAs can influence tumor behavior. One such lncRNA is XIST, which plays a crucial role in the development of brain metastasis in BC by affecting both tumor cells and the tumor microenvironment. XIST downregulation enhances brain metastatic growth and immune suppression, while fludarabine has been identified as a potential therapeutic agent that specifically targets XIST low tumor cells and effectively blocks brain metastasis [81]. Another lncRNA, BM, promotes brain metastases in BC by enhancing the JAK2 kinase activity and STAT3 signaling. This pathway facilitates vascular co-option and macrophage recruitment, which further supports metastasis [82]. ANCR regulates EZH2 stability by enhancing its interaction with CDK1, leading to EZH2 phosphorylation, ubiquitination, and degradation. ANCR's reduction promotes BC progression and metastasis, while its overexpression suppresses tumor formation and lung metastasis [83]. Moreover, BMP/OP-Responsive Gene (BORG) drives aggressive behaviors and metastasis in BC by enhancing breast cancer stem cell (BCSC) traits through interaction with the E3 SUMO ligase TRIM28. A high BORG expression correlates with increased metastatic potential and poor outcomes, while inhibiting BORG reduces metastasis and impacts BCSC phenotypes [84; 85]. It was found that nuclear factor-\(\kappa\)B interacting lncRNA (NKILA) expression was significantly reduced in invasive and metastatic breast cancer compared to benign and ductal carcinoma in situ tissues. Lower NKILA levels are associated with advanced disease stages, higher histopathological grades, and poorer patient survival [86]. NKILA's role in modulating the TGF-\(\beta\)-induced EMT and its inverse relationship with miR-103 and miR-107 suggest that NKILA could serve as a valuable independent prognostic marker for BC progression [87]. In a study by [PERSON] et al., Androgen receptor negatively induced lncRNA (ARNILA) was associated with dismal PFS in TNBC. ARNILA promotes the EMT, invasion, and metastasis to lung and liver by acting as a ceRNA for miR-204, thereby upregulating Sox4 and contributing to TNBC progression [88]. Another study revealed that linc-ROR was upregulated in BC and drove the EMT process, enhancing cancer cell migration, invasion, and lung metastasis in vivo. It functioned as a ceRNA for miR-205, stabilizing EMT-related genes like ZEB2 [89]. Furthermore, a significant difference was detected between the levels of linc-ROR expression and BC LNM [90]. The research by [PERSON] et al. identified that the plasma levels of lncRNAs Antisense noncoding RNA in the INK4 locus (ANRIL), hypoxia-inducible factor 1 alpha antisense (RNA-2 HIF1A-AS2), and urothelial carcinoma-associated 1 (UCA1) were significantly higher in patients with TNBC compared to those with non-TNBC and healthy controls. These lncRNAs showed strong diagnostic capabilities for TNBC, with AUC values of 0.785, 0.739, and 0.817, respectively. Elevated levels of these lncRNAs were also linked to increased LNM. The combined TNBCSigLnc-3 score, incorporating ANRIL, HIF1A-AS2, and UCA1, demonstrated the highest diagnostic accuracy with an AUC of 0.934, underscoring their potential as biomarkers for TNBC diagnosis and progression monitoring [91]. Similarly, another study revealed that UCA 1 and AC026904.1 acted synergistically to amplify TGF-\(\beta\)-induced activation of SNAI2, thereby promoting metastatic progression through the EMT process [92]. Moreover, the upregulation of Nicotinamide phosphoribosyltransferase (NAMPT-AS) in TNBC correlates with poor prognosis, larger tumor size, LN involvement, metastasis, and advanced stage.