Identification of circulating microRNAs during the liver neoplastic process in a murine model of hereditary tyrosinemia type 1.
Hereditary tyrosinemia type 1 (HT1) is a severe inborn error of metabolism, impacting the tyrosine catabolic pathway with a high incidence of hepatocellular carcinoma (HCC). Using a HT1 murine model, we investigated the changes in profiles of circulating and hepatic miRNAs. The aim was to determine if plasma miRNAs could be used as non-invasive markers of liver damage in HT1 progression. Plasma and liver miRNAome was determined by deep sequencing after HT1 phenotype was induced. Sequencing analysis revealed deregulation of several miRNAs including let-7/miR-98 family, miR-21 and miR-148a, during manifestation of liver pathology. Three miRNAs (miR-98, miR-200b, miR-409) presenting the highest plasmatic variations among miRNAs found in both plasma and liver and with >1000 reads in at least one plasma sample, were further validated by RT-qPCR. Two of these miRNAs have protein targets involved in HT1 and significant changes in their circulating levels are detectable prior an increase in protein expression of alpha-fetoprotein, the current biomarker for HCC diagnosis. Future assessment of these miRNAs in HT1 patients and their association with liver neoplastic lesions might designate these molecules as potential biomarkers for monitoring HT1 damage progression, improving diagnosis for early HCC detection and the design of novel therapeutic targets.
Laboratoire de génétique cellulaire et développementale, IBIS and PROTEO, Département de biologie moléculaire, biochimie médicale et pathologie, Faculté de médecine, 1030 avenue de la Médecine, Université Laval, Québec, Canada, G1V 0A6.|Dept of Occupational and Environmental Health and Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Francesca
F
Angileri
Laboratoire de génétique cellulaire et développementale, IBIS and PROTEO, Département de biologie moléculaire, biochimie médicale et pathologie, Faculté de médecine, 1030 avenue de la Médecine, Université Laval, Québec, Canada, G1V 0A6.
Geneviève
G
Morrow
Anipath, Faculté Laennec, rue Guillaume Paradin, 69372 Lyon Cedex 08, France.
Jean-Yves
JY
Scoazec
Anipath, Faculté Laennec, rue Guillaume Paradin, 69372 Lyon Cedex 08, France.
Nicolas
N
Gadot
Laboratoire de génétique cellulaire et développementale, IBIS and PROTEO, Département de biologie moléculaire, biochimie médicale et pathologie, Faculté de médecine, 1030 avenue de la Médecine, Université Laval, Québec, Canada, G1V 0A6.
Vincent
V
Roy
Dept of Occupational and Environmental Health and Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.|Key Laboratory of Molecular Biology of Shenzhen, Center for Disease Control and Prevention, Shenzhen, 518055, Guangdong, China.
Suli
S
Huang
Dept of Occupational and Environmental Health and Key Laboratory of Environment and Health, Ministry of Education and State Key Laboratory of Environmental Health (Incubating), School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Tangchun
T
Wu
Laboratoire de génétique cellulaire et développementale, IBIS and PROTEO, Département de biologie moléculaire, biochimie médicale et pathologie, Faculté de médecine, 1030 avenue de la Médecine, Université Laval, Québec, Canada, G1V 0A6.
Robert M
RM
Tanguay
D000818:Animals; D014408:Biomarkers, Tumor / Q000097:blood; D006528:Carcinoma, Hepatocellular / Q000097:blood / Q000235:genetics / Q000473:pathology; D000074166:Circulating MicroRNA / Q000235:genetics*; D004195:Disease Models, Animal; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D008099:Liver / Q000473:pathology*; D008113:Liver Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D020176:Tyrosinemias / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D000509:alpha-Fetoproteins / Q000235:genetics
D014408:Biomarkers, Tumor; D000074166:Circulating MicroRNA; D000509:alpha-Fetoproteins