@Article{096504017X15016337254605,
AUTHOR = {Liang Li, Huijuan Liu, Lianjiang Du, Pan Xi, Qian Wang, Yanqin Li, Di Liu},
TITLE = {miR-449a Suppresses LDHA-Mediated Glycolysis to Enhance  the Sensitivity of Non-Small Cell Lung Cancer Cells to Ionizing Radiation},
JOURNAL = {Oncology Research},
VOLUME = {26},
YEAR = {2018},
NUMBER = {4},
PAGES = {547--556},
URL = {http://www.techscience.com/or/v26n4/56667},
ISSN = {1555-3906},
ABSTRACT = {MicroRNA dysregulation contributes to malignant progression, dissemination, and profound treatment resistance in multiple cancers. miR-449a is recognized as a tumor suppresser. However, the roles of miR-449a in 
lung cancer initiation and progression are largely unknown. Our study aims to investigate the roles and underlying mechanism of miR-449a in modulating sensitivity to ionizing radiation (IR) in non-small cell lung cancer 
(NSCLC). Lung cancer cells were transfected with miR-449a mimics or negative control and exposed to IR; 
the levels of target protein, glycolysis, cell viability, apoptosis, and DNA damage were examined. miR-449a 
was suppressed in lung cancer tissues and cancer cells (A549 and H1299). IR exposure significantly increased 
the expression of miR-449a in A549 cells at doses ranging from 4 to 8 Gy at 24 h, whereas no significant 
change in miR-449a was found in H1299 cells after IR. When A549 cells were exposed to IR at a dose of 
8 Gy, the miR-449a level only had an acute increase within 12 h. miR-449a restoration dramatically suppressed 
IR-induced cell apoptosis and DNA damage in both A549 and H1299 cells. Bioinformatics analysis indicated 
that lactate dehydrogenase A (LDHA) was a potential target of miR-449a. miR-449a mimic transfection substantially suppressed the LDHA expression and production of lactate catalyzed by LDHA as well as glucose 
uptake. We confirmed that miR-449a could bind to the 3'-UTR of LDHA mRNA using luciferase reporter 
assay. LDHA siRNA-transfected cells showed enhanced cell apoptosis and DNA damage in response to IR 
exposure. miR-449a upregulation enhanced IR sensitivity of lung cancer cells by suppressing LDHA and the 
subsequent glycolysis.},
DOI = {10.3727/096504017X15016337254605}
}