The regulatory and predictive functions of miR-17 and miR-92 families on cisplatin resistance of non-small cell lung cancer.
BACKGROUND
Chemotherapy is an important therapeutic approach for non-small cell lung cancer (NSCLC). However, a successful long-term treatment can be prevented by the occurring of chemotherapy resistance frequently, and the molecular mechanisms of chemotherapy resistance in NSCLC remain unclear. In this study, abnormal expressions of miR-17 and miR-92 families are observed in cisplatin-resistant cells, suggesting that miR-17 and miR-92 families are involved in the regulation of cisplatin resistance in NSCLC.


METHODS
miRNA microarray shows that miR-17 and miR-92 families are all down-regulated in cisplatin-resistant A549/DDP cells compared with cisplatin-sensitive A549 cells. The aim of this study is to investigate the regulatory functions of miR-17 and miR-92 families on the formation of cisplatin resistance and the predictive functions of them as biomarkers of platinum-based chemotherapy resistance in NSCLC.


RESULTS
The low expressions of miR-17 and miR-92 families can maintain cisplatin resistance through the regulation of CDKN1A and RAD21. As a result of high expressions of CDKN1A and RAD21, the inhibition of DNA synthesis and the repair of DNA damage are achieved and these may be two major contributing factors to cisplatin resistance. Moreover, we demonstrate that the expressions of miR-17 and miR-92 families in NSCLC tissues are significantly associated with platinum-based chemotherapy response.


CONCLUSIONS
Our study indicates that miR-17 and miR-92 families play important roles in cisplatin resistance and can be used as potential biomarkers for better predicting the clinical response to platinum-based chemotherapy in NSCLC.
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China. zj_hjh@163.com.
Jian
J
Zhao
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China. 312342986@qq.com.
Wenfan
W
Fu
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China. hylmed1996@tom.com.
Hongying
H
Liao
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China. daes2004@qq.com.
Lu
L
Dai
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China. 505738383@qq.com.
Zeyong
Z
Jiang
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China. 153144068@qq.com.
Youguang
Y
Pan
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China. hhd_wong@163.com.
Haoda
H
Huang
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China. moyijun911@sina.com.
Yijun
Y
Mo
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China. 1016068999@qq.com.
Siwen
S
Li
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China. 429075483@qq.com.
Guangping
G
Yang
Department of Chest Surgery, Cancer Center of Guangzhou Medical University, Guangzhou, Guangdong, China. tottijun@163.com.
Jun
J
Yin
D020413:3' Untranslated Regions; D000970:Antineoplastic Agents / Q000494:pharmacology*; D001483:Base Sequence; D001665:Binding Sites; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000737:chemistry / Q000235:genetics; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D009687:Nuclear Proteins / Q000737:chemistry / Q000235:genetics; D010750:Phosphoproteins / Q000737:chemistry / Q000235:genetics; D012333:RNA, Messenger / Q000737:chemistry / Q000235:genetics
D020413:3' Untranslated Regions; D000970:Antineoplastic Agents; D018797:Cell Cycle Proteins; D050759:Cyclin-Dependent Kinase Inhibitor p21; D004268:DNA-Binding Proteins; C524941:MIRN17 microRNA, human; C541874:MIRN92 microRNA, human; D035683:MicroRNAs; D009687:Nuclear Proteins; D010750:Phosphoproteins; C429022:RAD21 protein, human; D012333:RNA, Messenger; D002945:Cisplatin