Hypoxia‐Induced FUS–circTBC1D14 Stress Granules Promote Autophagy in TNBC

Abstract

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.

Integrated transcriptomic and metabolomic analysis reveals the metabolic programming of GM-CSF- and M-CSF- differentiated mouse macrophages

“…Beyond the aspect of cell respiration, in the result of potential connection between metabolic genes and phagocytotic functions, Lamp1, a member of lysosome-associated membrane glycoproteins involving in autophagy process ( 56 ), and Clec genes (Clec7a, Clec4d, and Clec4e), which belongs to C-type lectin receptors participating in pathogens clearance ( 57 ), stand out in our data. Autophagy is a pathway by which macrophages eliminate pathogens, and the autophagy flux is closely related with cellular metabolism ( 58 , 59 ).…”

LINC00323 induced by hypoxia promote cartilage callus by interacting with FUS to regulate PDGFB expression

“…LINC00323 interacted with FUS to increase the stability of PDGFB mRNA FUS has been reported to regulate the mRNA stability of downstream target genes, but genes mediated by FUS remained largely unknown [20,23]. A GEO dataset, GSE226245, was downloaded from the database to analyze differentially expressed genes (DEGs).…”

Protein aggregation and biomolecular condensation in hypoxic environments (Review)

“…A study by Attwood et al ( 160 ) showed that hypoxia increased the number of late apoptotic/necrotic glioblastoma cells during the raloxifene-induced delay in SG dissolution. Liu et al ( 161 ) provided that hypoxic conditions could result in FUS-circTBC1D14-associated SG formation in the cytoplasm after PRMT1 modification, thus contributing to the maintenance of cellular homeostasis and promoting tumor progression in triple-negative breast cancer.…”