Decreased MiR-155 Level in the Peripheral Blood of Non-Alcoholic Fatty Liver Disease Patients may Serve as a Biomarker and may Influence LXR Activity.
BACKGROUND
Obesity is now a common risk factor for non-alcoholic fatty liver disease (NAFLD). Thus, it is important to explore its underlying mechanisms.


METHODS
Total RNA was extracted from peripheral whole blood samples from 50 NAFLD patients and 50 healthy controls. In addition, human liver specimens were obtained through liver biopsies from NAFLD patients and healthy controls. The level of miRNA was studied using real-time PCR. The expression of lipogenic genes was analyzed using western blot, and a dual luciferase reporter assay was conducted to identify the possible target gene. Adenovirus vectors were injected into the tail vein of the high fat diet (HFD)-fed mice to study the role of miR-155 on lipid accumulation in vivo.


RESULTS
The level of miR-155 was markedly reduced in the livers and peripheral blood of NAFLD patients compared with healthy controls. Upregulation of miR-155 decreased intracellular lipid content and the SREBP1 and FAS protein levels, while inhibition of miR-155 enhanced the intracellular lipid content. The dual luciferase reporter assay showed that Liver X receptor (LXR)α was the target gene of miR-155, and silencing miR-155 reduced the expression of SREBP1 and FAS. An in vivo study showed that upregulation of miR-155 decreased the hepatic lipid accumulation mainly by suppressing the LXRα-dependent lipogenic signaling pathway.


CONCLUSIONS
In summary, decreased expression of miR-155 in the peripheral blood may be utilized as a potential novel biomarker for NAFLD screening mainly by targeting LXRα.
Department of Rehabilitation Medicine, Second Medical School of Nanjing University of Chinese Medicine, Nanjing, China.
Lei
L
Wang
Ning
N
Zhang
Zun
Z
Wang
Dong-Mei
DM
Ai
Zhen-Yu
ZY
Cao
Hua-Ping
HP
Pan
D000818:Animals; D001483:Base Sequence; D015415:Biomarkers / Q000097:blood*; D016022:Case-Control Studies; D002460:Cell Line; D059305:Diet, High-Fat; D005260:Female; D020868:Gene Silencing / Q000187:drug effects; D006801:Humans; D050155:Lipogenesis / Q000187:drug effects / Q000235:genetics; D000071518:Liver X Receptors / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D008875:Middle Aged; D065626:Non-alcoholic Fatty Liver Disease / Q000097:blood* / Q000235:genetics*; D019301:Oleic Acid / Q000494:pharmacology; D019308:Palmitic Acid / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D015415:Biomarkers; D000071518:Liver X Receptors; C524942:MIRN155 microRNA, human; D035683:MicroRNAs; D019301:Oleic Acid; D019308:Palmitic Acid