[MiR-192 confers cisplatin resistance by targeting Bim in lung cancer].
OBJECTIVE
Cisplatin is the first-line drug for the chemotherapy of non-small cell lung cancer (NSCLC), but the acquired chemoresistance restricted the effect of its treatment. The aim of this study is to validate the miRNAs related to the Cisplatin resistance in lung cancer and elucidate the molecular mechanisms.


METHODS
We performed miRNA microarray and RT-PCR to obtain the aberrant differential expressed miRNAs between A549 and its paired Cisplatin-resistant cell line A549/DDP cells, and then we investigated the biological functions of miR-192, which is the aberrant differential expressed miRNA. After transfection of the miR-192 into A549 cells, we measured the half inhibition concentration (IC50), cell apoptosis of the trasfectant cells, and then we used biological softwares and dual-luciferase report assay to explore the target gene of the miR-192, which was further validated by RT-PCR and Western blot.


RESULTS
MiR-192 was highly over-expressed in A549/DDP cells , whose quantity was 37.59±0.35 fold higher than that in A549 cells. Overexpression of miR-192 in A549 cells significantly conferred resistance to Cisplatin and inhibited apoptosis. By contrast, down-expression of miR-192 in A549/DDP cells remarkably restrained the Cisplatin resistance and induced apoptosis. MiR-192 binded to Bim 3'-UTR and negatively regulated Bim expression at the post-transcriptional level in lung adenocarcinoma cells.


CONCLUSIONS
Our data suggested that miR-192 induced Cisplatin-resistance and inhibited cell apoptosis in lung cancer via negative targeting Bim expression.
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Fang
F
Zhang
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Yang
Y
Li
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Heng
H
Wu
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Kang
K
Qi
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Jiacong
J
You
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Xuebing
X
Li
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Lingling
L
Zu
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Zhenhua
Z
Pan
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Yuli
Y
Wang
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Yongwen
Y
Li
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Ying
Y
Li
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Min
M
Wang
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Wang
W
Shen
Tianjin Key Laboratory of Lung Cancer Metastasis and Tumor Microenvironment, Tianjin Lung Cancer Institute, Tianjin Medical University General Hospital, Tianjin 300052, China.
Qinghua
Q
Zhou
D020413:3' Untranslated Regions; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics* / Q000378:metabolism; D000072224:Bcl-2-Like Protein 11; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019008:Drug Resistance, Neoplasm; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics* / Q000378:metabolism
D020413:3' Untranslated Regions; D051017:Apoptosis Regulatory Proteins; C000606775:BCL2L11 protein, human; D000072224:Bcl-2-Like Protein 11; C546783:MIRN192 microRNA, human; D008565:Membrane Proteins; D035683:MicroRNAs; D011518:Proto-Oncogene Proteins; D002945:Cisplatin