Background: An increasing number of studies have shown that long noncoding RNAs (lncRNAs) play essential roles in tumor initiation and progression. LncRNAs act as tumor promoters or suppressors by targeting specific genes via epigenetic modifications and competing endogenous RNA (ceRNA) mechanisms. In this study, we explored the function and detailed mechanisms of long intergenic nonprotein coding RNA 673 (LINC00673) in breast cancer progression. Methods: Quantitative real-time PCR (qRT-PCR) was used to examine the expression of LINC00673 in breast cancer tissues and in adjacent normal tissues. Gain-of-function and loss-of function experiments were conducted to investigate the biological functions of LINC00673 in vitro and in vivo. We also explored the potential role of LINC00673 as a therapeutic target using antisense oligonucleotide (ASO) in vivo. RNA sequencing (RNA-seq), dual-luciferase reporter assays, chromatin immunoprecipitation (ChIP) assay, and rescue experiments were performed to uncover the detailed mechanism of LINC00673 in promoting breast cancer progression. Results: In the present study, LINC00673 displayed a trend of remarkably increased expression in breast cancer tissues and was associated with poor prognosis in breast cancer patients. Importantly, LINC00673 depletion inhibited breast cancer cell proliferation by inhibiting the cell cycle and increasing apoptosis. Furthermore, ASO therapy targeting LINC00673 substantially suppressed breast cancer cell proliferation in vivo. Mechanistically, LINC00673 was found to act as a ceRNA by sponging miR-515-5p to regulate MARK4 expression, thus inhibiting the Hippo signaling pathway. Finally, ChIP assay showed that the transcription factor Yin Yang 1 (YY1) could bind to the LINC00673 promoter and increase its transcription in cis. Conclusions: YY1-activated LINC00673 may exert an oncogenic function by acting as a sponge for miR-515-5p to upregulate the MARK4 and then inhibit Hippo signaling pathway, and may serve as a potential therapeutic target.

The immunosuppressive tumor microenvironment in triple-negative breast cancer could hinder the response to thorough immunotherapy and diminish the antitumor efficacy. Although the STING pathway emerges as a promising target to remedy defects, uncertain drug delivery might lead to off-target inflammatory reactions. Here, we manifest a novel phototheranostic agent with an aggregation-induced emission property that guided the pharmacological activation of a STING agonist for photothermal immunotherapy to create an immunologically "hot" tumor. A pyridinium rotor strategy is proposed to develop a positively charged TBTP-Bz, which is stably coincorporated with a STING agonist MSA-2 into thermal-responsive exosome-liposome hybrid nanoparticles for tumor-targeting delivery. TBTP-Bz exhibits aggregation-enhanced NIR-II emission and a photoacoustic signal, accomplishing real-time tumor tracking. Its photothermal stimulation induces immunogenic cancer cell death and promotes the precise release of MSA-2, thus boosting STING activation and STING-mediated type I interferon production. Significantly, single-dose photoimmunotherapy effectively suppresses abscopal tumor growth and provokes an immune memory effect to inhibit postsurgical recurrent and rechallenged tumors. This demonstrates promising clinical potential for poorly immunogenic breast cancer.

Pulmonary fibrosis (PF) is a chronic interstitial lung disorder characterized by abnormal myofibroblast activation, accumulation of extracellular matrix (ECM), and thickening of fibrotic alveolar walls, resulting in deteriorated lung function. PF is initiated by dysregulated wound healing processes triggered by factors such as excessive inflammation, oxidative stress, and coronavirus disease (COVID-19). Despite advancements in understanding the disease’s pathogenesis, effective preventive and therapeutic interventions are currently lacking. Ferroptosis, an iron-dependent regulated cell death (RCD) mechanism involving lipid peroxidation and glutathione (GSH) depletion, exhibits unique features distinct from other RCD forms (e.g., apoptosis, necrosis, and pyroptosis). Imbalance between reactive oxygen species (ROS) production and detoxification leads to ferroptosis, causing cellular dysfunction through lipid peroxidation, protein modifications, and DNA damage. Emerging evidence points to the crucial role of ferroptosis in PF progression, driving macrophage polarization, fibroblast proliferation, and ECM deposition, ultimately contributing to alveolar cell death and lung tissue scarring. This review provides a comprehensive overview of the latest findings on the involvement and signaling mechanisms of ferroptosis in PF pathogenesis, emphasizing potential novel anti-fibrotic therapeutic approaches targeting ferroptosis for PF management.

Organic radiosensitizers (ORSs), with structural versatility, hold promise for sensitizing radiotherapy (RT) by interacting with X‐ray photons to generate reactive oxygen species (ROS). They often consist of low‐Z elements that have inherently low X‐ray deposition capability. However, current ORSs suffer from short circulation half‐lives and low tumor retention, contradicting their requirements for sustained ROS generation upon RT in tumor sites. Herein, a glutathione‐responsive system is prepared, loaded with aggregation‐induced emission molecules (TPEPy‐I) and Ferriprotoporphyrin IX chloride (Hemin), to act as an ORS (named THN) for X‐ray triggered sustained ROS generation for efficient antitumor immunotherapy. In detail, THN effectively deposited X‐ray photons, which interact with water molecules to generate abundant ROS under external radiation. Subsequently, THN‐mediated radiosensitization stimulated tumor cells to produce hydrogen peroxide (H ₂ O ₂ ) by upregulating NOX4 protein, promoting the chemodynamic process of Hemin reacting with H ₂ O ₂ to continuously produce hydroxyl radicals. The double‐promoting ROS generation of THN induced massive immunogenic cancer cell death and polarized M2 macrophages into the M1 phenotype for enhanced antitumor immunotherapy. Experiments revealed that THN‐sensitized RT inhibited tumor recurrence and increased memory T‐cell proportion for long‐term antitumor immunity. The developed ORS has great clinical potential as both a radiosensitizer and a post‐RT immunomodulatory agent.