A novel regulatory network among LncRpa, CircRar1, MiR-671 and apoptotic genes promotes lead-induced neuronal cell apoptosis.
Lead is a metal that has toxic effects on the developing nervous system. However, the mechanisms underlying lead-induced neurotoxicity are not well understood. Non-coding RNAs (ncRNAs) play an important role in epigenetic regulation, but few studies have examined the function of ncRNAs in lead-induced neurotoxicity. We addressed this in the present study by evaluating the functions of a long non-coding RNA (named lncRpa) and a circular RNA (named circRar1) in a mouse model of lead-induced neurotoxicity. High-throughput RNA sequencing showed that both lncRpa and circRar1 promoted neuronal apoptosis. We also found that lncRpa and circRar1 induced the upregulation of apoptosis-associated factors caspase8 and p38 at the mRNA and protein levels via modulation of their common target microRNA miR-671. This is the first report of a regulatory interaction among a lncRNA, circRNA, and miRNA mediating neuronal apoptosis in response to lead toxicity.
State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, 511436, China.
Aruo
A
Nan
State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, 511436, China.
Lijian
L
Chen
State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, 511436, China.
Nan
N
Zhang
State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, 511436, China.
Zhenzhong
Z
Liu
State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, 511436, China.
Ti
T
Yang
Department of Physiology, Michigan State University, East Lansing, MI, 48824, USA.
Zhishan
Z
Wang
Department of Physiology, Michigan State University, East Lansing, MI, 48824, USA.|Institute for Integrative Toxicology, Michigan State University, East Lansing, MI, 48824, USA.
Chengfeng
C
Yang
State Key Laboratory of Respiratory Disease, Institute for Chemical Carcinogenesis, Guangzhou Medical University, Xinzao, Panyu District, Guangzhou, 511436, China. jiangyiguo@vip.163.com.
Yiguo
Y
Jiang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D053181:Caspase 8 / Q000235:genetics; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods; D051379:Mice; D035683:MicroRNAs / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics; D009474:Neurons / Q000187:drug effects*; D020258:Neurotoxicity Syndromes / Q000209:etiology* / Q000235:genetics; D009942:Organometallic Compounds / Q000633:toxicity*; D012313:RNA / Q000235:genetics; D000079962:RNA, Circular; D062085:RNA, Long Noncoding / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D048051:p38 Mitogen-Activated Protein Kinases / Q000235:genetics
C000597535:MIRN671 microRNA, mouse; D035683:MicroRNAs; D009942:Organometallic Compounds; D000079962:RNA, Circular; D062085:RNA, Long Noncoding; D012313:RNA; D048051:p38 Mitogen-Activated Protein Kinases; D053181:Caspase 8; C008261:lead acetate
Cell apoptosis; CircRNA; Lead; LncRNA; MiRNA; Neurotoxicity