PMID- 21984125
OWN - NLM
STAT- MEDLINE
DCOM- 20111128
LR  - 20230612
IS  - 1096-9896 (Electronic)
IS  - 0022-3417 (Print)
IS  - 0022-3417 (Linking)
VI  - 225
IP  - 3
DP  - 2011 Nov
TI  - Kaposi's sarcoma-associated herpesviral IL-6 and human IL-6 open reading frames 
      contain miRNA binding sites and are subject to cellular miRNA regulation.
PG  - 378-89
LID - 10.1002/path.2962 [doi]
AB  - Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a viral interleukin 6 
      (vIL-6) that mimics many activities of human IL-6 (hIL-6). Both vIL-6 and hIL-6 
      play important roles in stimulating the proliferation of tumours caused by KSHV. 
      Here, we provide evidence that a miRNA pathway is involved in regulation of vIL-6 
      and hIL-6 expression through binding sites in their open reading frames (ORFs). 
      We show a direct repression of vIL-6 by hsa-miR-1293 and hIL-6 by hsa-miR-608. 
      The repression of vIL-6 by miR-1293 was reversed by disruption of the vIL-6 
      miR-1293 seed match through the introduction of point mutations. In addition, 
      expression of vIL-6 or hIL-6 in KSHV-infected cells could be enhanced by 
      transfection of the respective miRNA inhibitors. In situ hybridization of human 
      lymph node sections revealed that miR-1293 is primarily expressed in the germinal 
      centre but is deficient in the mantle zone of lymph nodes, where the expression 
      of vIL-6 is often found in patients with KSHV-associated multicentric Castleman's 
      disease, providing evidence of an anatomical correlation. Taking these factors 
      together, our study indicates that IL-6 expression can be regulated by miRNA 
      interactions in its ORF and provides evidence for the role of these interactions 
      in the pathogenesis of KSHV-associated diseases.
CI  - Copyright (c) 2011 Pathological Society of Great Britain and Ireland. Published by 
      John Wiley & Sons, Ltd.
FAU - Kang, Jeong-Gu
AU  - Kang JG
AD  - HIV and AIDS Malignancy Branch, Center for Cancer Research, National Cancer 
      Institute, NIH, Bethesda, MD 20892, USA.
FAU - Majerciak, Vladimir
AU  - Majerciak V
FAU - Uldrick, Thomas S
AU  - Uldrick TS
FAU - Wang, Xiaohong
AU  - Wang X
FAU - Kruhlak, Michael
AU  - Kruhlak M
FAU - Yarchoan, Robert
AU  - Yarchoan R
FAU - Zheng, Zhi-Ming
AU  - Zheng ZM
LA  - eng
GR  - ZIA SC010357/ImNIH/Intramural NIH HHS/United States
GR  - ZIA SC010357-11/ImNIH/Intramural NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, N.I.H., Intramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20110824
PL  - England
TA  - J Pathol
JT  - The Journal of pathology
JID - 0204634
RN  - 0 (Interleukin-6)
RN  - 0 (MicroRNAs)
RN  - 0 (RNA, Viral)
RN  - 0 (Viral Proteins)
SB  - IM
MH  - Base Sequence
MH  - Binding Sites/genetics
MH  - Conserved Sequence
MH  - Gene Expression Regulation/*genetics
MH  - Gene Expression Regulation, Viral/genetics
MH  - Germinal Center/metabolism
MH  - HEK293 Cells
MH  - HeLa Cells
MH  - Herpesviridae Infections/genetics/metabolism
MH  - Herpesvirus 8, Human/genetics/*metabolism
MH  - Humans
MH  - Interleukin-6/*biosynthesis/genetics
MH  - Lymph Nodes/metabolism
MH  - MicroRNAs/genetics
MH  - Molecular Sequence Data
MH  - Open Reading Frames/genetics
MH  - RNA, Viral/genetics
MH  - Viral Proteins/biosynthesis/genetics
PMC - PMC3528401
MID - NIHMS423648
COIS- Conflict-of-interest disclosure: Dr. Giovanna Tosato, the spouse of one of the 
      authors, R.Y. is a co-inventor on a patent describing the measurement of KSHV 
      vIL6. This invention was made when G.T. was an employee of the US Government 
      under 45 Code of Federal Regulations Part 7. All rights, title, and interest to 
      this patent have been assigned to the U.S. Department of Health and Human 
      Services. The government conveys a portion of the royalties it receives to its 
      employee inventors under the Federal Technology Transfer Act of 1986 (P.L. 
      99-502).
EDAT- 2011/10/11 06:00
MHDA- 2011/12/13 00:00
PMCR- 2012/12/21
CRDT- 2011/10/11 06:00
PHST- 2010/11/17 00:00 [received]
PHST- 2011/05/29 00:00 [revised]
PHST- 2011/06/30 00:00 [accepted]
PHST- 2011/10/11 06:00 [entrez]
PHST- 2011/10/11 06:00 [pubmed]
PHST- 2011/12/13 00:00 [medline]
PHST- 2012/12/21 00:00 [pmc-release]
AID - 10.1002/path.2962 [doi]
PST - ppublish
SO  - J Pathol. 2011 Nov;225(3):378-89. doi: 10.1002/path.2962. Epub 2011 Aug 24.