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Triple‐negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that is suggested to be associated with hypoxia. This study is the first to identify a novel circular RNA (circRNA), circTBC1D14, whose expression is significantly upregulated in TNBC. The authors confirm that high circTBC1D14 expression is associated with a poor prognosis in patients with breast cancer. circTBC1D14‐associated mass spectrometry and RNA‐binding protein‐related bioinformatics strategies indicate that FUS can interact with circTBC1D14, which can bind to the downstream flanking sequence of circTBC1D14 to induce cyclization. FUS is an essential biomarker associated with stress granules (SGs), and the authors find that hypoxic conditions can induce FUS–circTBC1D14‐associated SG formation in the cytoplasm after modification by protein PRMT1. Subsequently, circTBC1D14 increases the stability of PRMT1 by inhibiting its K48‐regulated polyubiquitination, leading to the upregulation of PRMT1 expression. In addition, FUS–circTBC1D14 SGs can initiate a cascade of SG‐linked proteins to recognize and control the elimination of SGs by recruiting LAMP1 and enhancing lysosome‐associated autophagy flux, thus contributing to the maintenance of cellular homeostasis and promoting tumor progression in TNBC. Overall, these findings reveal that circTBC1D14 is a potential prognostic indicator that can serve as a therapeutic target for TNBC treatment. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs), one of the dominating constituents of tumor microenvironment, are important contributors to cancer progression and treatment resistance. Therefore, regulation of TAMs polarization from M2 phenotype towards M1 phenotype has emerged as a new strategy for tumor immunotherapy. Herein, we successfully initiated antitumor immunotherapy by inhibiting TAMs M2 polarization via autophagy intervention with polyethylene glycol-conjugated gold nanoparticles (PEG-AuNPs). PEG-AuNPs suppressed TAMs M2 polarization in both in vitro and in vivo models, elicited antitumor immunotherapy and inhibited subcutaneous tumor growth in mice. As demonstrated by the mRFP-GFP-LC3 assay and analyzing the autophagy-related proteins (LC3, beclin1 and P62), PEG-AuNPs induced autophagic flux inhibition in TAMs, which is attributed to the PEG-AuNPs induced lysosome alkalization and membrane permeabilization. Besides, TAMs were prone to polarize towards M2 phenotype following autophagy activation, whereas inhibition of autophagic flux could reduce the M2 polarization of TAMs. Our results revealed a mechanism underlying PEG-AuNPs induced antitumor immunotherapy, where PEG-AuNPs reduce TAMs M2 polarization via induction of lysosome dysfunction and autophagic flux inhibition. This study elucidated the biological effects of nanomaterials on TAMs polarization and provided insight into harnessing the intrinsic immunomodulation capacity of nanomaterials for effective cancer treatment. [Display omitted] [ABSTRACT FROM AUTHOR]

Aim: To improve the suboptimal therapeutic efficacy of salinomycin (SAL) toward liver cancer cells using chloroquine (CQ) combination by the liposomes co-delivering SAL and CQ (SCNL). Materials & methods: The synergy of these two drugs was evaluated in liver cancer cells (HepG2) and liver cancer stem cells (LCSCs) by median-effect analysis. SCNL with optimized ratio were developed. The cytotoxic effect and basal autophagy flux (measure of autophagic degradation activity) of various formulations were evaluated. Results & conclusion: CQ could significantly increase the cytotoxic effect of SAL in HepG2 cells, but not in HepG2-LCSCs, due to the greater basal autophagy flux in HepG2 cells. This combination therapy is promising for liver cancer treatment by eradicating liver cancer cells and LCSCs. [ABSTRACT FROM AUTHOR]