Differential microRNA profiling in a cellular hypoxia reoxygenation model upon posthypoxic propofol treatment reveals alterations in autophagy signaling network.
Recent studies indicate that propofol may protect cells via suppressing autophagic cell death caused by excessive reactive oxygen species induced by hypoxia reoxygenation (H/R). It is established that gene expression patterns including autophagy-related genes changed significantly during the process of H/R in the presence or absence of propofol posthypoxia treatment (P-PostH). The reasons for such differences, however, remain largely unknown. MicroRNAs provide a novel mechanism for gene regulation. In the present study, we systematically analyzed the alterations in microRNA expression using human umbilical vein endothelial cells (HUVECs) subjected to H/R in the presence or absence of posthypoxic propofol treatment. Genome-wide profiling of microRNAs was then conducted using microRNA microarray. Fourteen miRNAs are differentially expressed and six of them were validated by the quantitative real-time PCR (Q-PCR) of which three were substantially increased, whereas one was decreased. To gain an unbiased global perspective on subsequent regulation by altered miRNAs, predicted targets of ten miRNAs were analyzed using the Gene Ontology (GO) analysis to build signaling networks. Interestingly, six of the identified microRNAs are known to target autophagy-related genes. In conclusion, our results revealed that different miRNA expression patterns are induced by propofol posthypoxia treatment in H/R and the alterations in miRNA expression patterns are implicated in regulating distinctive autophagy-related gene expression.
Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Zhuo
Z
Chen
Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Zhe
Z
Hu
Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Zhiqi
Z
Lu
Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Shuyun
S
Cai
Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Xiaoxia
X
Gu
Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Haixia
H
Zhuang
Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Zhihua
Z
Ruan
Anesthesiology Research Laboratory, Department of Anesthesiology, University of Hong Kong, Hong Kong.
Zhengyuan
Z
Xia
Anesthesiology Research Laboratory, Department of Anesthesiology, University of Hong Kong, Hong Kong.
Michael G
MG
Irwin
Key Laboratory of Age-Associated Cardiac-Cerebral Vascular Disease of Guangdong Province, Department of Neurology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Du
D
Feng
Department of Anesthesiology, Affiliated Hospital of Guangdong Medical College, Zhanjiang 524001, China.
Liangqing
L
Zhang
D001343:Autophagy / Q000187:drug effects / Q000235:genetics*; D015687:Cell Hypoxia / Q000187:drug effects / Q000235:genetics; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects; D053263:Gene Regulatory Networks; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D020411:Oligonucleotide Array Sequence Analysis; D010100:Oxygen / Q000494:pharmacology*; D015742:Propofol / Q000494:pharmacology*; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects / Q000235:genetics*
D035683:MicroRNAs; D010100:Oxygen; D015742:Propofol