Skip to main content
construction release_alert
Scholars@Duke will be undergoing maintenance April 11-15. Some features may be unavailable during this time.
cancel

The LINK-A lncRNA interacts with PtdIns(3,4,5)P3 to hyperactivate AKT and confer resistance to AKT inhibitors.

Publication ,  Journal Article
Lin, A; Hu, Q; Li, C; Xing, Z; Ma, G; Wang, C; Li, J; Ye, Y; Yao, J; Liang, K; Wang, S; Park, PK; Marks, JR; Zhou, Y; Zhou, J; Hung, M-C ...
Published in: Nat Cell Biol
March 2017

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Nat Cell Biol

DOI

EISSN

1476-4679

Publication Date

March 2017

Volume

19

Issue

3

Start / End Page

238 / 251

Location

England

Related Subject Headings

  • Triple Negative Breast Neoplasms
  • Risk Factors
  • RNA, Long Noncoding
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase Inhibitors
  • Phosphorylation
  • Phosphatidylinositol Phosphates
  • Nucleic Acid Conformation
  • Mutation
  • Lipids
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Lin, A., Hu, Q., Li, C., Xing, Z., Ma, G., Wang, C., … Yang, L. (2017). The LINK-A lncRNA interacts with PtdIns(3,4,5)P3 to hyperactivate AKT and confer resistance to AKT inhibitors. Nat Cell Biol, 19(3), 238–251. https://doi.org/10.1038/ncb3473
Lin, Aifu, Qingsong Hu, Chunlai Li, Zhen Xing, Guolin Ma, Cheng Wang, Jun Li, et al. “The LINK-A lncRNA interacts with PtdIns(3,4,5)P3 to hyperactivate AKT and confer resistance to AKT inhibitors.Nat Cell Biol 19, no. 3 (March 2017): 238–51. https://doi.org/10.1038/ncb3473.
Lin A, Hu Q, Li C, Xing Z, Ma G, Wang C, et al. The LINK-A lncRNA interacts with PtdIns(3,4,5)P3 to hyperactivate AKT and confer resistance to AKT inhibitors. Nat Cell Biol. 2017 Mar;19(3):238–51.
Lin, Aifu, et al. “The LINK-A lncRNA interacts with PtdIns(3,4,5)P3 to hyperactivate AKT and confer resistance to AKT inhibitors.Nat Cell Biol, vol. 19, no. 3, Mar. 2017, pp. 238–51. Pubmed, doi:10.1038/ncb3473.
Lin A, Hu Q, Li C, Xing Z, Ma G, Wang C, Li J, Ye Y, Yao J, Liang K, Wang S, Park PK, Marks JR, Zhou Y, Zhou J, Hung M-C, Liang H, Hu Z, Shen H, Hawke DH, Han L, Lin C, Yang L. The LINK-A lncRNA interacts with PtdIns(3,4,5)P3 to hyperactivate AKT and confer resistance to AKT inhibitors. Nat Cell Biol. 2017 Mar;19(3):238–251.

Published In

Nat Cell Biol

DOI

EISSN

1476-4679

Publication Date

March 2017

Volume

19

Issue

3

Start / End Page

238 / 251

Location

England

Related Subject Headings

  • Triple Negative Breast Neoplasms
  • Risk Factors
  • RNA, Long Noncoding
  • Proto-Oncogene Proteins c-akt
  • Protein Kinase Inhibitors
  • Phosphorylation
  • Phosphatidylinositol Phosphates
  • Nucleic Acid Conformation
  • Mutation
  • Lipids