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245	1	0	_aThe LINK-A lncRNA interacts with PtdIns(3,4,5)P3 to hyperactivate AKT and confer resistance to AKT inhibitors
490	0		_vNature Cell Biology, 19(3), p.238, 2017
520	3		_aPhosphatidylinositol-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.
700	1	2	_aLin, A.
700	1	2	_aHu, Q.
700	1	2	_aLi, C.
700	1	2	_aXing, Z.
700	1	2	_aMa, G.
700	1	2	_aWang, C.
700	1	2	_aLi, J.
700	1	2	_aLi, J.
700	1	2	_aYao, J.
700	1	2	_aLiang, S.
700	1	2	_aWang, S.
700	1	2	_aPark, P. K.
700	1	2	_aMarks, J. R.
700	1	2	_aZhou, Y.
700	1	2	_aZhou, J.
700	1	2	_aHung, M-C.
700	1	2	_aLiang, H.,
700	1	2	_aHu, Z.
700	1	2	_aShen, H.
700	1	2	_aHawke, D. H.
700	1	2	_aHan, L.
700	1	2	_aZhou, Y
700	1	2	_aLin, C
700	1	2	_aYang, L.
856	4	0	_uhttps://drive.google.com/file/d/1xccpj-9jebyHZjQlVp-SCMoj73q7Hy7c/view?usp=drivesdk _zPara ver el documento ingresa a Google con tu cuenta: @cicy.edu.mx
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