Mechanistic study on the inhibition of triple-negative breast cancer progression by LncRNA TFAP2A-AS1 through the regulation of miR-6892/PHGDH.

Abstract

Background: The roles of long non-coding RNAs (lncRNAs) in the progression of various human tumors have been extensively studied. However, their specific mechanisms and therapeutic potential in Triple-Negative Breast Cancer (TNBC) remain to be fully elucidated.

Materials and methods: The qRT-PCR assay was utilized to assess the relative mRNA levels of TFAP2A-AS1, PHGDH, and miR-6892. To investigate the impact of TFAP2A-AS1, we conducted various assays, including CCK-8, Transwell, flow cytometry, and clonal formation assays, to analyze cell viability, invasion, apoptosis, and proliferation capabilities of TNBC cells. Additionally, the effects of TFAP2A-AS1 on tumor growth were evaluated through in vivo xenograft models. To explore and confirm the interactions between TFAP2A-AS1 and miR-6892, as well as between miR-6892 and PHGDH, we employed bioinformatics analysis and dual-luciferase reporter assays. Lastly, Western blot analysis and immunohistochemistry (IHC) were performed to determine the protein expression levels of PHGDH and EMT-related markers in treated TNBC cells and xenograft tissues.

Results: Our study revealed that TFAP2A-AS1 was notably downregulated in TNBC cell lines, whereas PHGDH was upregulated. High PHGDH expression correlated with poorer survival outcomes, suggesting its oncogenic role in TNBC. Functional assays demonstrated that overexpression of TFAP2A-AS1 suppressed proliferation, clonal formation, migration, and invasion, while promoting apoptosis in TNBC cells. Conversely, overexpression of PHGDH had the opposite effects, promoting tumorigenic traits. Mechanistically, TFAP2A-AS1 was found to act as a sponge for miR-6892, thereby upregulating its expression and subsequently inhibiting the target gene PHGDH. In vivo experiments confirmed that TFAP2A-AS1 overexpression inhibited tumor growth, an effect that was partially reversed by the inhibition of miR-6892 or overexpression of PHGDH.

Conclusion: Our study demonstrates that lncRNA TFAP2A-AS1 inhibits TNBC progression by modulating the miR-6892/PHGDH axis. These findings reveal that TFAP2A-AS1 suppresses key malignant characteristics of TNBC, such as proliferation, migration, and invasion. These insights suggest that targeting this pathway could offer a potential therapeutic strategy for TNBC, a subtype known for its limited targeted treatment options.