TY  - BOOK
AU  - Lin,A.
AU  - Hu,Q.
AU  - Li,C.
AU  - Xing,Z.
AU  - Ma,G.
AU  - Wang,C.
AU  - Li,J.
AU  - Li,J.
AU  - Yao,J.
AU  - Liang,S.
AU  - Wang,S.
AU  - Park,P.K.
AU  - Marks,J.R.
AU  - Zhou,Y.
AU  - Zhou,J.
AU  - Hung,M-C.
AU  - Liang,H.
AU  - Hu,Z.
AU  - Shen,H.
AU  - Hawke,D.H.
AU  - Han,L.
AU  - Zhou,Y
AU  - Lin,C
AU  - Yang,L.
TI  - The LINK-A lncRNA interacts with PtdIns(3,4,5)P3 to hyperactivate AKT and confer resistance to AKT inhibitors
N2  - 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
UR  - https://drive.google.com/file/d/1xccpj-9jebyHZjQlVp-SCMoj73q7Hy7c/view?usp=drivesdk
ER  -