Abstract |
A role for microRNAs ( miRNA) in human T-cell leukemia virus 1 (HTLV-1)-mediated cellular transformation has not been described. Here, we profiled miRNA expression in HTLV-1-transformed human T-cell lines and primary peripheral blood mononuclear cells from adult T-cell leukemia patients. Analyses of 11 different profiles revealed six miRNAs that were consistently up-regulated. Two of the up-regulated miRNAs (miR-93 and miR-130b) target the 3' untranslated region ( 3'UTR) of the mRNA for a tumor suppressor protein, tumor protein 53-induced nuclear protein 1 (TP53INP1). A low expression level of TP53INP1 protein was found in HTLV-1-transformed cells. Additionally, when antagomirs were used to knock down miR-93 and miR-130b in these cells, the expression of TP53INP1 was increased, suggesting that the latter is regulated inside cells by the former. A role for TP53INP1 in regulating cell growth was established by experiments that showed that enhanced TP53INP1 expression increased apoptosis. Collectively, the findings implicate a miR-93/miR-130b-TP53INP1 axis that affects the proliferation and survival of HTLV-1-infected/transformed cells.
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Authors | Man Lung Yeung, Jun-ichirou Yasunaga, Yamina Bennasser, Nelson Dusetti, David Harris, Nafees Ahmad, Masao Matsuoka, Kuan-Teh Jeang |
Journal | Cancer research
(Cancer Res)
Vol. 68
Issue 21
Pg. 8976-85
(Nov 01 2008)
ISSN: 1538-7445 [Electronic] United States |
PMID | 18974142
(Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural)
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Chemical References |
- 3' Untranslated Regions
- Carrier Proteins
- DNA Primers
- Heat-Shock Proteins
- MicroRNAs
- TP53INP1 protein, human
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Topics |
- 3' Untranslated Regions
- Base Sequence
- Carrier Proteins
(genetics, physiology)
- Cell Division
(physiology)
- Cell Line, Transformed
- DNA Primers
- Heat-Shock Proteins
(genetics, physiology)
- Human T-lymphotropic virus 1
(physiology)
- In Situ Nick-End Labeling
- Leukemia
(genetics)
- MicroRNAs
(genetics, physiology)
- Polymerase Chain Reaction
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