bims-meluca 2026-09-13 papers

Biochem Biophys Res Commun. 2026 Sep 04. pii: S0006-291X(26)01311-2. [Epub ahead of print]836 154547

RUNX2 regulates cell proliferation, autophagy activity and apoptosis in LUAD cell via transcriptionally activating TMEM74.

Ji Zhang, Yuan-Zhuang Xia, Bo Huang, Yong He.

Lung cancer has the highest mortality rate of all cancers, and lung adenocarcinoma (LUAD) is one of the most common subtypes. TMEM74 expression is upregulated in both lung cancer patients and LUAD cell lines, and its high expression correlates with poor patient survival. Targeted TMEM74 knockdown and overexpression vectors were successfully constructed, and stably transfected LUAD cell lines were established. TMEM74 was found to significantly enhance LUAD cell proliferation and colony formation while suppressing apoptosis. TMEM74 overexpression elevated the LC3II/I ratio, reduced p62 levels, and boosted autolysosome formation, whereas TMEM74 knockdown exerted opposite effects. Bafilomycin A1-mediated autophagy inhibition abrogated the pro-proliferative and anti-apoptotic effects driven by TMEM74 overexpression. Subcutaneous xenograft experiments revealed that TMEM74 knockdown restrained tumor growth, and impaired autophagic activity in tumor. A positive correlation was observed between the expression levels of Runt-related transcription factor 2 (RUNX2) and TMEM74 in LUAD. RUNX2 overexpression in LUAD cells induced upregulation of TMEM74 mRNA levels. Dual luciferase reporter assays demonstrated that RUNX2 significantly enhanced the transcriptional activity of TMEM74 in LUAD cells. TMEM74 knockdown reversed the increased cell proliferation, reduced apoptosis and enhanced autophagosome formation induced by RUNX2 overexpression in LUAD cells. Collectively, our experimental results demonstrate that RUNX2 transcriptionally activates TMEM74, thereby promoting LUAD cell proliferation and autophagy and inhibiting cell apoptosis in vitro; TMEM74 knockdown suppresses tumor growth in vivo.

Keywords: Apoptosis; Autophagy; Lung adenocarcinoma; RUNX2; TMEM74

DOI: https://doi.org/10.1016/j.bbrc.2026.154547

Med Oncol. 2026 Sep 08. pii: 270. [Epub ahead of print]43(10):

Spatially resolved lactate-glycolysis transcriptional programs are associated with neutrophil-enriched immune remodeling in lung adenocarcinoma.

Yixian Liang, Jing Tan, Jiali Zhang, Binyu Wang, Danfei Shi, Longfei Ji, Xinmin Li, Daojun Yu, Yong Li.

Metabolic reprogramming characterized by enhanced glycolysis and lactate production plays a critical role in tumor progression and immune regulation. However, the cellular distribution and spatial organization of lactate-glycolysis activity within the lung adenocarcinoma (LUAD) microenvironment remain incompletely understood. We integrated single-cell RNA sequencing, spatial transcriptomics, and bulk transcriptomic datasets from TCGA and GEO cohorts to characterize lactate-glycolysis-associated metabolic heterogeneity in LUAD. AUCell-based scoring was used to quantify metabolic activity at single-cell resolution. Associations with immune infiltration and clinical outcomes were evaluated, and key findings were validated using spatial transcriptomics, quantitative PCR, and immunohistochemistry. Cells exhibiting high lactate-glycolysis activity were predominantly enriched in fibroblasts and neutrophils, indicating that this metabolic program extends beyond malignant cells. A metabolism-associated gene signature, comprising RPS2, GAPDH, and LDHA, was consistently correlated with immune remodeling and an unfavorable prognosis. Spatial transcriptomics further revealed the co-localization of GAPDH and LDHA with neutrophil-enriched regions. These findings were supported by experimental validation in clinical specimens. Our study reveals that lactate-glycolysis reprogramming in LUAD is spatially structured and closely associated with neutrophil-enriched immune remodeling. This metabolism-associated immune regulatory pattern provides insight into the organization of the tumor microenvironment and may have implications for metabolic- and immune-oriented therapeutic strategies in lung adenocarcinoma.

Keywords: Glycolysis; Lactate metabolism; Lung adenocarcinoma; Single-cell transcriptome; Spatial transcriptome; Tumor immune microenvironment

DOI: https://doi.org/10.1007/s12032-026-03390-8

Mol Biol Rep. 2026 Sep 05. pii: 1528. [Epub ahead of print]53(1):

Recent advancements in NRF2-regulated ferroptosis modulation for targeted cancer therapy.

Ozge Cemiloglu Ulker, Antonella Capozzi, Nisa Nur Sari-Goktas, Maurizio Sorice, Luciano Saso, Brigitta Buttari.

The nuclear factor erythroid 2-related factor 2 (NRF2) signaling pathway is a major regulator of cellular response to oxidative stress. While NRF2 protects the normal cells against oxidative stress, its abnormal signaling activity in the context of cancer helps tumor cells evade oxidative stress, survive, proliferate, and develop resistance to treatment. Increasing evidence has established the tight connection between NRF2 signaling and ferroptosis, a type of programmed cell death based on iron-dependent lipid oxidation. In this review, the role of NRF2 in regulating important pathways as glutathione metabolism, lipid peroxidation, and iron homeostasis that contribute to the process of ferroptosis is discussed. This review highlights the latest progress that has been made in therapies that are designed to target the NRF2-ferroptosis pathway in cancers, by providing an overview of the mechanism involved as well as relevant pre-clinical and current clinical studies. The latest advancements regarding the NRF2 modulators and ferroptosis inducers, both natural and synthetic, along with new studies regarding the ability of such compounds to overcome drug resistance and increase antitumor effectiveness are reviewed.In addition, it is addressed current studies in biomarker discovery, precision medicine, drug targeting in terms of future direction. Moreover, the existing limitations related to clinical application of NRF2 and ferroptosis modulation therapies are also described, including tumor heterogeneity, treatment selectivity, biomarker validation, and possible toxicity of such therapy to normal tissue.Overall, these developments provide the rationale for the clinical application of the NRF2-ferroptosis pathway as a therapeutic target in overcoming drug resistance.

Keywords: Cancer therapy; Ferroptosis; Lipid peroxidation; NRF2 pathway; Precision oncology

DOI: https://doi.org/10.1007/s11033-026-12705-x