Feedback circuitry via let-7c between lncRNA CCAT1 and c-Myc is involved in cigarette smoke extract-induced malignant transformation of HBE cells.
Cigarette smoking is a primary risk factor for the development of lung cancer, which is regarded as the leading cause of cancer-related deaths. The process of malignant transformation of cells, however, is complex and elusive. The present study investigated the roles of an lncRNA, CCAT1, and a transcriptional factor, c-Myc, in human bronchial epithelial (HBE) cell transformation induced by cigarette smoke extract. With acute and chronic treatment of HBE cells, cigarette smoke extract induced increases of CCAT1 and c-Myc levels and decreases of levels of let-7c, a microRNA. Down-regulation of c-Myc reduced the degree of malignancy and the invasion/migration capacity of HBE cells transformed by cigarette smoke extract. ChIP assays established that c-Myc, increased by cigarette smoke extract, binds to the promoter of CCAT1, activating its transcription. Further, let-7c suppressed the expression of c-Myc through binding to its 3'-UTR. In turn, CCAT1 promoted the accumulation of c-Myc through binding to let-7c and decreasing free let-7c, which influenced the neoplastic capacity of HBE cells transformed by cigarette smoke extract. These results indicate that a positive feedback loop ensures expression of cigarette smoke extract-induced CCAT1 and c-Myc via let-7c, which is involved in cigarette smoke extract-induced malignant transformation of HBE cells. Thus, the present research establishes a new mechanism for the reciprocal regulation between CCAT1 and c-Myc and provides an understanding of cigarette smoke extract-induced lung carcinogenesis.
Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.
Lu
L
Lu
Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.
Hong
H
Qi
Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.
Fei
F
Luo
Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.
Hui
H
Xu
Jiangsu Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, People's Republic China.
Min
M
Ling
Jiangsu Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, People's Republic China.
Yu
Y
Qin
The School of Public Health, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 510182, Guangdong, People's Republic China.
Ping
P
Yang
Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.
Xinlu
X
Liu
Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.
Qianlei
Q
Yang
Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.
Junchao
J
Xue
Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.
Chao
C
Chen
The School of Public Health, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Guangzhou 510182, Guangdong, People's Republic China.
Jiachun
J
Lu
Jiangsu Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, People's Republic China.
Quanyong
Q
Xiang
Institute of Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.|The Key Laboratory of Modern Toxicology, Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, Jiangsu, People's Republic of China.
Qizhan
Q
Liu
Jiangsu Center for Disease Control and Prevention, Nanjing 210009, Jiangsu, People's Republic China.
Qian
Q
Bian
D017209:Apoptosis; D001980:Bronchi / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D004847:Epithelial Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D025461:Feedback, Physiological; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D035683:MicroRNAs / Q000235:genetics*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D062085:RNA, Long Noncoding / Q000235:genetics*; D012907:Smoking / Q000009:adverse effects*
C579842:CCAT1 long noncoding RNA, human; C489427:MYC protein, human; D035683:MicroRNAs; D016271:Proto-Oncogene Proteins c-myc; D062085:RNA, Long Noncoding; C487931:mirnlet7 microRNA, human
carcinogenesis; cigarette smoke extract (CSE); lncRNAs; lung cancer; miRNAs