# An Emerging Role of Long Noncoding RNAs as Novel Biomarkers for Breast Cancer Metastasis
## 5 Potential lncRNA-Based Biomarkers
### Malat1  
Following HOTAIR, one of the most extensively studied lncRNAs in BC is MALAT1. It is located on chromosome 11q13.1 and was originally identified as a transcript associated with lung cancer metastasis but was later found to be overexpressed in other types of cancers as well, including BC. MALAT-1 regulates gene expression by interacting with gene ends and participating in active transcriptional elongation. It also influences pre-mRNA alternative splicing through the control of serine/arginine splicing factor phosphorylation and acts as a post-transcriptional regulator through a competing endogenous RNA (ceRNA) mechanism. By using miRNA-responsive elements, MALAT-1 communicates with mRNAs and pseudogenes, leading to changes in cell behavior like invasion and metastasis. Another mechanism involves BC exosomes promoting cell proliferation, with MALAT1 inducing cell proliferation through exosomes [36]. The crucial role of MALAT1 expression in the EMT process has been confirmed in several studies. [PERSON] et al. observed a reciprocal repression between MALAT1 and miR-204, with Zinc Finger E-Box Binding Homeobox 2 (ZEB2) identified as a downstream target of miR-204, mediating MALAT1's function through the miR-204/ZEB2 axis. ZEB2 can trigger the EMT by directly suppressing E-cadherin. Moreover, higher MALAT1 expression correlated with poorer overall survival, especially in patients with advanced tumors [16]. [PERSON] et al. showed that reducing MALAT1 expression in MCF-7 cells significantly inhibited proliferation, migration, and tube formation. They also found a negative correlation between miR-145 and MALAT1 expression in BC tissues. Furthermore, the knockdown of MALAT1 significantly decreased the expression of Vascular Endothelial Growth Factor (VEGF) [37]. Despite the consistent elevation of MALAT1 levels in the luminal subtype and relatively lower levels in TNBC subtypes, [PERSON] et al. demonstrated that MALAT1 promoted proliferation, progression, and metastasis in TNBC as well. Elevated MALAT1 expression was associated with decreased survival in ER-negative, LN-negative patients of the HER2 and TNBC subtypes, with MALAT1 showing independent prognostic significance in TNBC LN-negative patients. These findings suggest the potential of MALAT1 as a predictive marker for metastatic disease onset in LN-negative patients considered low risk for metastasis [38]. Analyzing samples from 240 patients who were histopathologically diagnosed with TNBC, [PERSON] et al. discovered that BTB and CNC Homology 1 (BACH1) and MALAT1 were simultaneously upregulated in cancerous tissues. Individuals with elevated expression levels of MALAT1 and BACH1 displayed characteristics such as larger tumor size, LNM, and advanced TNM. These findings suggest that MALAT1 and BACH1 may play critical roles and serve as potential markers in the carcinogenesis and progression of TNBC [39]. The expression of MALAT1 in triple-negative and HER-2-positive BC positively correlated with the number of metastatic LNs. Furthermore, MALAT1 emerged as an independent prognostic factor for these metastases. It promoted proliferation and invasion via the X-box Binding Protein 1(XBP1)-hypoxia-inducible factor-1\(\alpha\) (HIF) pathway in MDA-MB-231 and the HER-2 pathway in MDA-MD-435 [40]. In a study of [PERSON] et al., MALAT1 expression was significantly upregulated in 85.9% of BC tissues collected from 78 patients compared to normal tissues, and its elevation was associated with LNM and adverse 5-year disease-free survival (DFS). Furthermore, serum MALAT1 levels were significantly higher in BC patients compared to those with benign breast disease and showed satisfactory diagnostic efficacy with an AUC of 0.833 [41]. Contrary to the above findings, there are also studies examining the role of MALAT1 not as a promoter but as a suppressor of metastasis in BC. [PERSON] et al. discovered that MALAT1 overexpression inhibited BC metastasis, while MALAT1 deficiency induced them, reversible by reintroducing MALAT1.