Associative memory plays a role in ER-1α positive breast cancers.

Tumor suppressor BAP1 emerges as a key regulator of metabolism and cell death in tumors

An integrated overview of the molecular features and functional roles of BAP1 is provided, with particular emphasis on its impacts on the regulation of cell death including apoptosis, ferroptosis and disulfidptosis.

LncRNA-mediated organization of oncogenic chromatin state is a targetable vulnerability in leukemia

This study uncovers a therapeutic vulnerable lncRNA-centric circuitry and provides compelling preclinical evidence for the development and application of a novel RNA targeting-LNP based therapy for treatment of myeloid leukemia.

Upregulation of ITM2A by p53 activation modulates p53 function through physical interaction.

The tumor suppressor p53 plays a crucial role in preventing cancer development, and its dysfunction is frequently observed in various cancers. This study identifies a novel regulatory interaction between p53 and ITM2A. We found that p53 upregulates ITM2A expression, while ITM2A in turn inhibits p53 function, suggesting a negative feedback loop. ITM2A mRNA levels were reduced across multiple tumor types, particularly in those harboring mutant p53, and low ITM2A expression correlated with poor patient survival. Mechanistically, ITM2A physically interacts with p53, selectively modulates its phosphorylation (reducing Ser392 while enhancing Ser37), and promotes cytoplasmic accumulation of p53. These modifications collectively suppress p53-dependent transcription, an effect consistently observed across multiple cell lines under both basal conditions and upon physiological p53 activation by genotoxic stress. Conversely, ITM2A depletion enhances p53 nuclear accumulation and transcriptional activity. These findings reveal a novel autoregulatory circuit wherein p53 induces ITM2A expression, which then attenuates p53 activity, suggesting ITM2A as a potential prognostic marker and therapeutic target for cancers with dysregulated p53 signaling.

Functional interplay between TTP/ZFP36 and HuR/ELAVL1 in cancer: a post-transcriptional regulatory network

Post-transcriptional regulation of gene expression has emerged as a fundamental determinant of cancer initiation, progression, and therapeutic response. Among the RNA-binding proteins (RBPs) involved in mRNA turnover and translational regulation, tristetraprolin (TTP), encoded by the ZFP36 gene, and “Human antigen R” (HuR), encoded by ELAVL1, represent two functionally antagonistic regulators of AU-rich element (ARE)-containing transcripts. TTP promotes the degradation of target mRNAs through recruitment of deadenylation and decay complexes, whereas HuR generally stabilizes and enhances the translation of overlapping mRNA subsets. Because many oncogenic, inflammatory, angiogenic, and metastasis-associated transcripts contain AREs within their 3′ untranslated regions, the balance between TTP-mediated decay and HuR-mediated stabilization critically influences tumor biology. Accumulating evidence demonstrates that loss of TTP expression or activity and cytoplasmic accumulation of HuR are recurrent features across multiple cancer types, including breast, colorectal, pancreatic, gastric, liver, ovarian, and lung cancers. Importantly, several studies indicate that the reciprocal interplay between these proteins establishes a post-transcriptional rheostat controlling cancer-associated RNA regulons. This review summarizes current knowledge regarding the molecular biology of TTP and HuR, emphasizing their opposing functions in mRNA metabolism and cancer progression. We discuss mechanisms regulating their expression, localization, phosphorylation, and RNA-binding activity; analyze cancer-specific evidence; and examine models in which both proteins are co-expressed or functionally interconnected. Finally, we evaluate therapeutic strategies aimed at restoring TTP function or inhibiting HuR activity and discuss future perspectives for targeting post-transcriptional regulatory networks in oncology.

The lncRNA CTD-2566 J3.1 orchestrates oncogenic gene regulation via chromatin interactions in luminal breast cancer.

These findings establish CTD-2566 J3.1 as a multifunctional enhancer-associated lncRNA (e-lncRNA) that orchestrates key oncogenic processes in luminal breast cancer and underscores the utility of three-dimensional culture systems to reveal context-specific lncRNA functions.

IRES-mediated translation of Δ160p53 regulates p53 functions and fine-tunes cancer homeostasis