Circular RNAs (circRNAs) are increasingly gaining importance and attention due to their diverse potential functions and their value as diagnostic biomarkers (disease specific). This study aims to explore the novel mechanisms by which exosome-contained circRNAs promote tumor development and metastasis in TNBC. We identified increased circRNA circPSMA1 in TNBC cells, their exosomes, and serum exosomes samples from TNBC patients. The overexpression of circPSMA1 promoted TNBC cell proliferation, migration, and metastasis both in vitro and in vivo. Moreover, we investigated the tumor-infiltrating immune cells (TICs) or stromal components in immune microenvironment (IME), and identified the significant differences in the immune cells between TNBC and non-TNBC samples. Mechanistically, circPSMA1 acted as a “miRNAs sponge” to absorb miR-637; miR-637 inhibited TNBC cell migration and metastasis by directly targeted Akt1, which recognized as a key immune-related gene and affected downstream genes β-catenin and cyclin D1. Subsequent co-culture experiments also demonstrated that exosomes from TNBC carrying large amounts of circPSMA1 could transmit migration and proliferation capacity to recipient cells. Kaplan–Meier plots showed that high expression of Akt1 and low expression of mir-637 are highly correlated with poor prognosis in patients with lymph node metastasis of TNBC. Collectively, all these results reveal that circPSMA1 functions as a tumor promoter through the circPSMA1/miR-637/Akt1-β-catenin (cyclin D1) regulatory axis, which can facilitate the tumorigenesis, metastasis, and immunosuppression of TNBC. Our research proposes a fresh perspective on novel potential biomarkers and immune treatment strategies for TNBC.
Previous studies have reported that angelicin exerted antiproliferative effects on several types of tumor cell. However, to the best of our knowledge, the effects of angelicin monotherapy on human liver cancer remain to be investigated. In the present study, the antitumor activity of angelicin was evaluated in vitro and in vivo, and the molecular mechanisms underlying its effects were investigated. The present results revealed that angelicin induced apoptosis in liver cancer cells in a dose- and time-dependent manner. Furthermore, in HepG2 and Huh-7 cells, angelicin-induced apoptosis was demonstrated to be mitochondria dependent, involving the phosphatidylinositol-4,5-bisphosphate 3-kinase/RAC-α serine/threonine-protein kinase signaling pathway. In addition, administration of angelicin to mice bearing liver tumor xenografts inhibited tumor growth, without producing significant secondary adverse effects. These results suggested that angelicin may have potential as a novel therapeutic agent for the treatment of patients with liver cancer.
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