RRC ID 37900
Author Nakamura S, Kahyo T, Tao H, Shibata K, Kurabe N, Yamada H, Shinmura K, Ohnishi K, Sugimura H.
Title Novel roles for LIX1L in promoting cancer cell proliferation through ROS1-mediated LIX1L phosphorylation.
Journal Sci Rep
Abstract Herein, we report the characterization of Limb expression 1-like, (LIX1L), a putative RNA-binding protein (RBP) containing a double-stranded RNA binding motif, which is highly expressed in various cancer tissues. Analysis of MALDI-TOF/TOF mass spectrometry and RNA immunoprecipitation-sequencing of interacting proteins and the microRNAs (miRNAs) bound to LIX1L revealed that LIX1L interacts with proteins (RIOK1, nucleolin and PABPC4) and miRNAs (has-miRNA-520a-5p, -300, -216b, -326, -190a, -548b-3p, -7-5p and -1296) in HEK-293 cells. Moreover, the reduction of phosphorylated Tyr(136) (pTyr(136)) in LIX1L through the homeodomain peptide, PY136, inhibited LIX1L-induced cell proliferation in vitro, and PY136 inhibited MKN45 cell proliferation in vivo. We also determined the miRNA-targeted genes and showed that was apoptosis induced through the reduction of pTyr(136). Moreover, ROS1, HCK, ABL1, ABL2, JAK3, LCK and TYR03 were identified as candidate kinases responsible for the phosphorylation of Tyr(136) of LIX1L. These data provide novel insights into the biological significance of LIX1L, suggesting that this protein might be an RBP, with implications for therapeutic approaches for targeting LIX1L in LIX1L-expressing cancer cells.
Volume 5
Pages 13474
Published 2015-8-27
DOI 10.1038/srep13474
PII srep13474
PMID 26310847
PMC PMC4550850
MeSH Actin Depolymerizing Factors / metabolism Amino Acid Sequence Animals Antineoplastic Agents / pharmacology Apoptosis / drug effects Apoptosis / genetics Blotting, Western Cell Line, Tumor Cell Proliferation / drug effects Electrophoresis, Gel, Two-Dimensional Enzyme Assays Gene Knockdown Techniques High-Throughput Nucleotide Sequencing Immunohistochemistry Mass Spectrometry Mice, Nude MicroRNAs / genetics MicroRNAs / metabolism Molecular Sequence Data Peptides / chemistry Peptides / pharmacology Phosphorylation / drug effects Protein-Tyrosine Kinases / metabolism* Proteomics Proto-Oncogene Proteins / metabolism* RNA-Binding Proteins / metabolism* Software Stomach Neoplasms / metabolism* Stomach Neoplasms / pathology* Xenograft Model Antitumor Assays
IF 4.011
Times Cited 1
Human and Animal Cells NUGC-4(RCB1939) MKN45(RCB1001)