Lysophosphatidic Acid Receptor 6 (LPAR6) Expression and Prospective Signaling Pathway Analysis in Breast Cancer

Abstract

Background and Objective: Lysophosphatidic acid (LPA) has widely been reported to participate in the numerous biological behaviors of tumors through its receptors. LPA receptor 6 (LPAR6) is a newly identified G protein-coupled receptor of LPA, and few studies have explored the role of LPAR6 in cancer. In breast cancer (BC), LPAR6 has not, as yet, been studied. This study aimed to evaluate LPAR6 expression in BC patients and to explore its possible role in BC. Methods: A total of 98 pairs of clinical BC and para-cancer tissues were collected, and LPAR6 expression was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). Kaplan-Meier plots were employed for survival analysis. Human BC cell lines were cultured to study decitabine (5-aza-2ʹ-deoxycytidine [5-Aza]) intervention. Bioinformatic analyses were carried out to support the study conclusions and predictions. Results: LPAR6 expression was significantly reduced in BC tissues (p < 0.001). In the analysis of clinical parameters, LPAR6 expression was related to BC molecular classification (p < 0.05). Furthermore, patients with higher LPAR6 expression had better prognoses (p < 0.001). The CpG islands of LPAR6 were hypermethylated in BC tissues relative to those in para-cancer tissues (p < 0.01). 5-Aza significantly upregulated LPAR6 expression in BC cell lines. Additionally, LPAR6 knockdown significantly promoted cell migration and proliferation in the ZR-75-1 cell line (p < 0.001). Finally, through Gene Set Enrichment Analysis (GSEA), LPAR6 was found to be negatively correlated with cancer-promoting factors and positively correlated with tumor-suppressing factors. Conclusion: LPAR6 was downregulated in BC, and low LPAR6 expression was related to poor prognosis. The anti-tumor drug 5-Aza significantly upregulated LPAR6 expression in vitro, and LPAR6 might act as a tumor suppressor in BC.