Lin, A. Hu, Q. Li, C. Xing, Z. Ma, G. Wang, C. Li, J. Li, J. Yao, J. Liang, S. Wang, S. Park, P. K. Marks, J. R. Zhou, Y. Zhou, J. Hung, M-C. Liang, H. Hu, Z. Shen, H. Hawke, D. H. Han, L. Zhou, Y Lin, C Yang, L. text xx 9999 monographic und

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Phosphatidylinositol-3,4,5-trisphosphate (PtdIns(3,4,5)P3 or PIP3)mediates signalling pathways as a second messenger in response to extracellular signals. Although primordial functions of phospholipids and RNAs have been hypothesized in the 'RNA world', physiological RNA-phospholipid interactions and their involvement in essential cellular processes have remained a mystery. We explicate the contribution of lipid-binding long non-coding RNAs (lncRNAs)in cancer cells. Among them, long intergenic non-coding RNA for kinase activation (LINK-A)directly interacts with the AKT pleckstrin homology domain and PIP3 at the single-nucleotide level, facilitating AKT-PIP3 interaction and consequent enzymatic activation. LINK-A-dependent AKT hyperactivation leads to tumorigenesis and resistance to AKT inhibitors. Genomic deletions of the LINK-A PIP3-binding motif dramatically sensitized breast cancer cells to AKT inhibitors. Furthermore, meta-analysis showed the correlation between LINK-A expression and incidence of a single nucleotide polymorphism (rs12095274: A > G), AKT phosphorylation status, and poor outcomes for breast and lung cancer patients. PIP3-binding lncRNA modulates AKT activation with broad clinical implications. https://drive.google.com/file/d/1xccpj-9jebyHZjQlVp-SCMoj73q7Hy7c/view?usp=drivesdk https://drive.google.com/file/d/1xccpj-9jebyHZjQlVp-SCMoj73q7Hy7c/view?usp=drivesdk 250602 20260521091557.0