Super enhancer lncRNA RP11-54O7.17 regulates the proliferation and metastasis of triple-negative breast cancer by targeting lysosomal degradation of S100A4

Abstract Triple-negative breast cancer (TNBC) is characterized by its high aggressiveness and treatment resistance, with limited therapeutic options and especially a lack of effective targeted therapeutic strategies. This study focuses on the role and regulatory mechanisms of super enhancer long non-coding RNA (SE-lncRNA) in TNBC. Through in-depth analysis of TCGA database, we revealed the specific expression pattern of SE-lncRNA in TNBC, and found that downregulation of RP11-54O7.17 was significantly correlated with poor prognosis of TNBC patients, which was experimentally verified. Both in vitro and in vivo results confirmed that RP11-54O7.17 overexpression effectively suppressed the proliferation and metastasis of TNBC. Further exploration showed that RP11-54O7.17 directly interacted with the S100A4 protein through its conserved L2b-type repeat structural fragment, promoted S100A4 binding to HSP70, targeting S100A4 degradation via the autophagy-lysosome pathway, which in turn blocked the activation of S100A4-STAT3 signaling axis. Moreover, RP11-54O7.17 delivered via liposome demonstrated significant anti-TNBC efficacy in an in vivo model without observing significant systemic toxicity. This study elucidates the regulatory role and molecular mechanism of RP11-54O7.17 in TNBC, which provides a strong scientific basis and potential therapeutic targets for the development of novel SE-lncRNA-based therapeutic strategies.