Cancer Cell International最新文献

PVT1 is a non-coding RNA (ncRNA) playing an important role in various biological processes, including cell survival, differentiation, proliferation, and chromatin regulation. Overexpression of PVT1 improve a proliferation rate even for 30% and reduces the level of apoptosis. It can act as a scaffold, decoy, guide, enhancer RNA, and it affects the entire gene life cycle through chromatin remodeling, epigenetic regulation, transcription, post-transcriptional control, and protein metabolism. PVT1 is a highly complex and multifunctional factor that plays a critical role in cancer development and progression through various mechanisms. Different PVT1 fusion transcripts have been identified in solid tumors and hematological malignancies. High expression of PVT1 is linked to advanced clinical stage, lymph node metastasis, and unfavorable overall survival in various types of human cancers. The manuscript represents extensive analysis and summary of the functions and mechanisms of PVT1 in the context of miRNAs and highlights possible ways to target PVT1 and the it signaling pathways. It is important to understand the intricate relationships between PVT1 and different types of human cancers to achieve a better understanding of the disease and treatment options. The current findings identify an upregulated PVT1 as a crucial promoter of the risk of carcinogenesis and tumor metastasis, also dramatically reducing patient survival, underscoring the potential of PVT1 expression as a prognostic marker in cancer.

Background: 8-Chloro-adenosine (8-Cl-Ado) is a promising antitumor agent, and ferroptosis plays a critical role in breast cancer progression. Our previous work demonstrated that 8-Cl-Ado inhibits breast cancer cell proliferation by targeting adenosine deaminase acting on RNA 1 (ADAR1), an RNA-editing enzyme. However, whether 8-Cl-Ado exerts its anti-tumor effects through the modulation of ferroptosis remains largely unknown.

Methods: The effects of 8-Cl-Ado on ferroptosis were assessed in vitro and in vivo. The molecular mechanisms of 8-Cl-Ado were investigated by performing bioinformatics analysis, RNA immunoprecipitation assay (RIP), luciferase reporter assay, fluorescence in situ hybridization (FISH), qRT-PCR, and western blotting.

Results: 8-Cl-Ado significantly inhibited the proliferation, migration, and invasion of MCF-7 and MDA-MB-231 breast cancer cells, while promoting ferroptosis, as evidenced by elevated levels of intracellular Fe²⁺, reactive oxygen species (ROS), and malondialdehyde (MDA), along with decreased glutathione (GSH) levels and reduced protein expression of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4). In an orthotopic breast cancer mouse model, 8-Cl-Ado suppressed tumor growth and decreased the expression of SLC7A11 and GPX4. Mechanistically, 8-Cl-Ado downregulated ADAR1 expression, resulting in upregulation of miR-101-3p, which directly targets the 3'UTR of SLC7A11 mRNA, leading to its degradation and subsequent induction of ferroptosis. Moreover, ADAR1 bound to the precursor of miR-101-3p and impairs its processing into mature miR-101-3p in an RNA editing-independent manner.

Conclusion: Our study identifies a novel pathway by which 8-Cl-Ado promotes ferroptosis through the ADAR1/miR-101-3p/SLC7A11 axis to suppress breast cancer progression. These findings highlight the therapeutic potential of 8-Cl-Ado as a ferroptosis-inducing agent by targeting ADAR1.

In their recent study, Li et al. (2025) propose a novel signaling axis in which GADD45GIP1 promotes osteosarcoma progression by stabilizing RPL35, thereby alleviating endoplasmic reticulum (ER) stress through the PERK/eIF2α pathway. While this work identifies a potentially significant oncogenic mechanism, our analysis highlights several critical aspects that require further elucidation. The central claim-that stabilization of a single ribosomal protein, RPL35, directly and specifically alleviates ER stress-presents a conceptual paradox, as enhanced ribosome biogenesis would typically be expected to increase the proteotoxic load. We explore alternative explanations, including the potential for selective mRNA translation or non-ribosomal functions of RPL35. Furthermore, the therapeutic promise of targeting this pathway is tempered by the challenges of inhibiting protein-protein interactions and the risk of on-target toxicity given the pervasive role of the PERK pathway in normal secretory cells. The model also necessitates validation across the spectrum of osteosarcoma's genetic heterogeneity. This letter critically examines these mechanistic ambiguities and proposes essential experiments to validate the model, assess its therapeutic viability, and define its clinical relevance within the complex landscape of osteosarcoma biology.