Selective killing of lung cancer cells by miRNA-506 molecule through inhibiting NF-κB p65 to evoke reactive oxygen species generation and p53 activation.
The tumor suppressor p53, nuclear factor-κB (NF-κB) and reactive oxygen species (ROS) have crucial roles in tumorigenesis, although the mechanisms of cross talk between these factors remain largely unknown. Here we report that miR-506 upregulation occurs in 83% of lung cancer patients (156 cases), and its expression highly correlates with ROS. Ectopic expression of miR-506 inhibits NF-κB p65 expression, induces ROS accumulation and then activates p53 to suppress lung cancer cell viability, but not in normal cells. Interestingly, p53 promotes miR-506 expression level, indicating that miR-506 mediates cross talk between p53, NF-κB p65 and ROS. Furthermore, we demonstrated that miR-506 mimics inhibited tumorigenesis in vivo, implicating that miR-506 might be a potential therapeutic molecule for selective killing of lung cancer cells.
1] The State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China [2] School of Life Science, University of Science and Technology of China, Hefei, China.
M
M
Yin
1] The State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China [2] School of Life Science, University of Science and Technology of China, Hefei, China.
X
X
Ren
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China.
X
X
Zhang
Guangzhou RiboBio Co., Ltd, Guangzhou, China.
Y
Y
Luo
The State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
G
G
Wang
Guangzhou RiboBio Co., Ltd, Guangzhou, China.
K
K
Huang
Guangzhou RiboBio Co., Ltd, Guangzhou, China.
S
S
Feng
The State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
X
X
Bao
University of Chinese Academy of Sciences, Beijing, China.
K
K
Huang
School of Life Science, University of Science and Technology of China, Hefei, China.
X
X
He
1] The State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China [2] University of Chinese Academy of Sciences, Beijing, China.
P
P
Liang
The State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China.
Z
Z
Wang
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China.
H
H
Tang
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Guangzhou Medical College, Guangzhou, China.
J
J
He
1] The State Key Laboratory of Respiratory Diseases, Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou, China [2] School of Life Science, University of Science and Technology of China, Hefei, China.
B
B
Zhang
D000818:Animals; D017209:Apoptosis; D063646:Carcinogenesis / Q000235:genetics; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000096:biosynthesis* / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics
C561508:MIRN506 microRNA, human; D035683:MicroRNAs; D016328:NF-kappa B; D017382:Reactive Oxygen Species; C495901:TP53 protein, human; D051996:Transcription Factor RelA; D016159:Tumor Suppressor Protein p53