Down-regulation of microRNA 106b is involved in p21-mediated cell cycle arrest in response to radiation in prostate cancer cells.
BACKGROUND
microRNAs (miRNAs) are endogenous short non-coding RNAs, and play a pivotal role in regulating of a variety of cellular processes, including proliferation and apoptosis, both of which are cellular responses to radiation treatment. The purpose of this study is to identify candidate miRNAs whose levels are altered in response to radiation in prostate cancer cells and to investigate the molecular pathway of such miRNAs in the regulation of radiation-induced cellular response.


METHODS
Using a miRNA microarray assay, we screened 132 cancerous miRNAs in LNCaP cells in response to radiation treatment. The function of one candidate miRNA was investigated for checkpoint protein expression, cell cycle arrest, cell proliferation, and cell survival in cells transfected with precursor or antisense miRNA.


RESULTS
In response to radiation, multiple miRNAs, including mi-106b, showed altered expression. Cells transfected with precursor miR-106b were able to suppress radiation-induced p21 activation. Functionally, exogenous addition of precursor miR-106b overrode the G2/M arrest in response to radiation and resulted in a transient diminishment of radiation-induced growth inhibition.


CONCLUSIONS
We have shown a novel role of miR-106b, in the setting of radiation treatment, in regulating the p21-activated cell cycle arrest. Our finding that miR-106b is able to override radiation-induced cell cycle arrest and cell growth inhibition points to a potential therapeutic target in certain prostate cancer cells whose radiation resistance is likely due to consistently elevated level of miR-106b.
Li
Baoqing
B
Department of Radiation Oncology, Weill Medical College of Cornell University, New York, New York 10065, USA. dr.baoli@gmail.com
Shi
Xu-Bao
XB
Nori
Dattatreyudu
D
Chao
Clifford K S
CK
Chen
Allen M
AM
Valicenti
Richard
R
White
Ralph de Vere
Rde V
D017209:Apoptosis / Q000502:physiology / Q000528:radiation effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics / Q000502:physiology / Q000528:radiation effects*; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000528:radiation effects*; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D046228:Microarray Analysis; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy*; D012313:RNA / Q000737:chemistry / Q000235:genetics; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054462:p21-Activated Kinases / Q000378:metabolism*
D035683:MicroRNAs; D012313:RNA; D054462:p21-Activated Kinases