# An Emerging Role of Long Noncoding RNAs as Novel Biomarkers for Breast Cancer Metastasis
## 5 Potential lncRNA-Based Biomarkers
### Gags  
Further contributing to the diverse roles of lncRNAs in BC and another potential biomarker is GAS5, a member of the 5'-terminal oligopyrimidine (5'-TOP) gene family, located at 1q25.1. It consists of 12 exons and contains a brief open reading frame devoid of protein-coding capacity. It undergoes alternative splicing, resulting in two mature forms of lncRNA: GAS5a and GAS5. The downregulation of its expression was found in various types of neoplasms such as prostatic, lung, gastric cancer, and gliomas [59]. Significantly lower levels of GAS5 were also detected in BC.  
In a study by [PERSON] et al., GAS5 showed reduced expression in trastuzumab-resistant SKBR-3/Tr cells and BC tissues from patients treated with trastuzumab, leading to increased cell proliferation and counteracting the inhibitory effects of lapatinib on proliferation. GAS5 was found to hinder the growth and invasion of BC by trapping oncogenic miR-21 and triggering the activation of its targets, including PTEN and Programmed Cell Death Protein 4 (PDCD4) [60]. GAS5 also interacts with miR-196a-5p to suppress TNBC progression, while miR-196a-5p targets Forkhead Box Protein O1 (FOXO1), a pivotal regulator of tumor growth and invasion. Notably, FOXPO1 also enhances GAS5 transcription, forming a positive feedback loop [61]. Furthermore, decreased levels of lncRNA-GAS5 facilitate BC metastasis to the lungs through the induction of the EMT process. The expression of GAS5 has a significant, yet not fully understood, impact on the processes of autophagy and apoptosis, which are crucial in the metastasis and treatment resistance of cancer cells. GAS5 has the potential to trigger apoptosis in TNBC cells by modulating the miR-378a-5p/Suppressor of Fused (SUFU) signaling pathway [62]. It was found to positively correlate with unc-51-like autophagy activating kinase (ULK) 1/2, key regulators of autophagy. Overexpression GAS5 inhibited cell proliferation, invasion, and tumor formation in BC cells, partially through autophagy induction [63]. Based on tissue samples obtained from 103 TNBC patients, [PERSON] et al. observed a significant decrease in GAS5 levels, which correlated with an aggressive tumor phenotype, including an advanced clinical stage, LNM, and poorer overall survival [61]. In research conducted by [PERSON] et al., plasma RNA was extracted from preoperative (n = 90) and postoperative (n = 39) BC patients, along with healthy controls (n = 76). While no significant differences were found between BC patients and controls in GAS5, it correlated with the Ki67 proliferation index in preoperative patients. postoperatively, GAS5 and H19 levels significantly decreased in 71.8% cases, with lower GAS5 levels associated with high Ki67 proliferation index pre-surgery and positive LNM post-surgery [64].  
On the contrary, [PERSON] et al. found that GAS5 expression was reduced in the serum of BC patients compared to both healthy individuals and non-cancer patients with a predisposition to BC. Moreover, decreased GAS5 levels were linked to unfavorable prognostic indicators such as metastasis and recurrence. The study findings revealed that GAS5 demonstrated a sensitivity of 72.5% and specificity of 78.5%, effectively distinguishing between normal and at-risk individuals [65]. Based on the discussions, GAS5 emerges as a potential marker for BC metastasis due to its downregulation in TNBC tissues and its association with aggressive tumor phenotypes [66]. Further research is needed to elucidate its mechanisms of action and validate its efficacy across diverse patient cohorts [12].