NEAT1-31 [Neurosurgery Wiki]

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====== NEAT1-31 ======
Li et al. identify a novel micropeptide, NEAT1-31, encoded by the long non-coding RNA LincNEAT1, significantly enhancing human macrophages' phagocytic capacity. Using in vitro phagocytosis assays, ribosome profiling, and phosphoproteomic analysis, the authors show that NEAT1-31 directly activates the Aurora-A kinase, leading to stimulation of the PI3K-AKT signaling pathway, which is known to regulate cytoskeletal rearrangement and phagocytosis. NEAT1-31 also synergizes with anti-CD47 therapy to enhance tumor cell clearance, highlighting its potential as an immunotherapeutic adjuvant
((Li J, Zhang J, Li X, Liu X, Zeng B, Luo J, Wang H, Zhang H, Gao X. LincNEAT1 Encoded-NEAT1-31 Promotes Phagocytosis by Directly Activating the Aurora-A-PI3K-AKT Pathway. Adv Sci (Weinh). 2025 May 8:e2413473. doi: 10.1002/advs.202413473. Epub ahead of print. PMID: 40344649.)).
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🧠 Critical Analysis

✅ Strengths

Novel Mechanism: Demonstrates that a presumed lncRNA can encode a functional peptide with direct immunomodulatory effects.

Mechanistic Clarity: Solid molecular pathway is proposed (NEAT1-31 → Aurora-A → PI3K-AKT → phagocytosis).

Translational Relevance: Enhances effect of anti-CD47, indicating possible clinical synergy in immunotherapy.

Robust methodology: Uses primary macrophages, ribosome profiling, phosphoproteomics, and in vivo validation.

❌ Limitations

Preclinical only: No pharmacokinetic or toxicity data; no human trials.

Delivery method unclear: It’s not specified how NEAT1-31 would be delivered efficiently in clinical settings.

Limited cancer types tested: Although claimed to act broadly, evidence is strongest for breast cancer models.

🔬 Implications

Redefines the dogma of non-coding RNAs by revealing a peptide with therapeutic potential.

Provides a blueprint for discovering other hidden immunoregulatory peptides within annotated lncRNAs.

May serve as a next-generation "eat-me" signal enhancer in the context of checkpoint blockade immunotherapy.