MicroRNA could modulate the development of nicotine dependence
A new research has unveiled a previously unrecognized role for microRNA in nicotine dependence. The research would help understand why it's so difficult for people to stop smoking.
A paper describing the research by a team of researchers from the University of Michigan in the USA and Huazhong University of Science and Technology in China, appears 7 November 2017 in the journal Cell Reports.
Cigarette smoking is a risk factor for a wide range of diseases such as cancer and cardiovascular diseases. Cigarette smoke contains a large number of harmful substances, including tar, nicotine, carbon monoxide, hydrogen cyanide, and ammonia. Of these harmful substances, nicotine is not the most harmful but is addictive. It is nicotine that makes it difficult to quit smoking. In attempts to stop smoking, the new ex-smokers experience a host of physical and psychological symptoms such as anxiety, irritability, frustration, anger, and depressed mood. These symptoms associated with nicotine withdrawal may result in failure of quit attempts.
To uncover the mechanisms of nicotine dependence/addition and to develop strategies to help people quit smoking, a lot of works have been done by scientists worldwide. It has long been established that chronic exposure to nicotine leads to an increase in nicotinic acetylcholine receptors (nAChRs), which is associated with nicotine dependence. But how nicotine increases nAChRs remains largely unknown.
X.Z. Shawn Xu, Ph.D., associate professor of molecular and integrative physiology at the University of Michigan, who is the corresponding author of the new research, has been studying some of the fundamental questions in neuroscience and physiology for years. In 2006, Dr. Xu and co-workers used the worm C. elegans as a model organism to investigate the genetic mechanisms of nicotine-dependent behavioral responses. They discovered that the worms exhibited behavioral responses to nicotine that parallel those observed in mammals, and that nAChR family genes, which are known to mediate nicotine dependence in mammals, are required for nicotine-dependent responses in the worms. These results suggest that C. elegans is a suitable model organism to identify and characterize genes regulating nicotine responses.
In the current study, Dr. Xu's team investigated how nicotine would affect nAChR expression at post-transcriptional level. MicroRNAs represent an important strategy of post-transcriptional regulation of gene expression in cells. MicroRNAs are small non-coding RNAs and inhibit gene expression by binding to mRNA. Until now, the role of microRNAs in nicotine dependence has not been defined.
Dr. Xu's team found that chronic nicotine exposure upregulates the transcripts of the nAChR genes acr-15 and acr-19. Moreover, they found that acr-19 plays a key role in mediating nicotine withdrawal response, and acr-15 acts upstream of acr-19 to regulate its expression. Notably, the study demonstrated that the microRNA machinery is important in modulating nicotine withdrawal response as well as for nicotine-induced upregulation of acr-19 expression. Collectively, these data support a possible link between nicotine, microRNA, nAChR expression, and nicotine-dependent behavior.
MicroRNAs are known to regulate diverse physiological and pathological processes. Further investigation is needed to better elucidate the regulatory roles of microRNAs in nAChR expression and nicotine-dependent behavior. Such research would one day lead to more effective solutions for the problem of smoking.