Expression and function of miRNA in postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer.
OBJECTIVE
To investigate the different miRNA expression profiles of postoperative radiotherapy sensitive and resistant patients of non-small cell lung cancer, explore their potential role and find some radio-sensitivity markers.


METHODS
Thirty non-small cell lung cancer patients who have been treated by postoperative radiotherapy were selected and were divided into radiotherapy sensitive group and resistant group according to overall survival and local or distant recurrence rate. Expression profile of miRNA in these two groups was detected by a microarray assay and the results were validated by quantitative RT-PCR and Northern blot. At the molecular level, the effect of one differently expressed miRNA (miR-126) on the growth and apoptosis of SK-MES-1 cells induced by irradiation was examined.


RESULTS
Comparing with resistant patients, five miRNAs (miRNA-126, miRNA-let-7a, miRNA-495, miRNA-451 and miRNA-128b) were significantly upregulated and seven miRNAs (miRNA-130a, miRNA-106b, miRNA-19b, miRNA-22, miRNA-15b, miRNA-17-5p and miRNA-21) were greatly downregulated in radiotherapy sensitive group. Overexpression of miRNA-126 inhibited the growth of SK-MES-1 cells and promoted its apoptosis induced by irradiation. The expression level of p-Akt decreased in miRNA-126 overexpression group. After treating with phosphoinositidyl-3 kinase (PI3K) constitutively activator (IGF-1) and inhibitor (LY294002), miRNA-126 overexpression had no significant effects on the apoptosis of SK-MES-1 cells.


CONCLUSIONS
We found 12 differently expressed miRNAs in the radiotherapy sensitive and resistant non-small cell lung cancer samples. Moreover, our results showed miRNA-126 promoted non-small cell lung cancer cells apoptosis induced by irradiation through the PI3K-Akt pathway.
Wang
Xiao-Chun
XC
Tianjin Key Laboratory of Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin 300192, China.
Du
Li-Qing
LQ
Tian
Li-Li
LL
Wu
Hai-Liang
HL
Jiang
Xiao-Yan
XY
Zhang
Heng
H
Li
De-Guan
DG
Wang
Yue-Ying
YY
Wu
Hong-Ying
HY
She
Yi
Y
Liu
Qing-Fen
QF
Fan
Fei-Yue
FY
Meng
Ai-Min
AM
D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy / Q000601:surgery; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism / Q000532:radiotherapy / Q000601:surgery; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D008875:Middle Aged; D051058:Oncogene Protein v-akt / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011184:Postoperative Period; D011836:Radiation Tolerance; D015398:Signal Transduction
D035683:MicroRNAs; D019869:Phosphatidylinositol 3-Kinases; D051058:Oncogene Protein v-akt