Roles for microRNAs, miR-93 and miR-130b, and tumor protein 53-induced nuclear protein 1 tumor suppressor in cell growth dysregulation by human T-cell lymphotrophic virus 1.
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.
Yeung
Man Lung
ML
Molecular Virology Section, Laboratory of Molecular Microbiology, National Institute of Allergy and Infectious Diseases, NIH, Bethesda, Maryland, USA.
Yasunaga
Jun-ichirou
J
Bennasser
Yamina
Y
Dusetti
Nelson
N
Harris
David
D
Ahmad
Nafees
N
Matsuoka
Masao
M
Jeang
Kuan-Teh
KT
D020413:3' Untranslated Regions; D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology*; D002455:Cell Division / Q000502:physiology*; D002461:Cell Line, Transformed; D017931:DNA Primers; D006360:Heat-Shock Proteins / Q000235:genetics / Q000502:physiology*; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D020287:In Situ Nick-End Labeling; D007938:Leukemia / Q000235:genetics; D035683:MicroRNAs / Q000235:genetics / Q000502:physiology*; D016133:Polymerase Chain Reaction
D020413:3' Untranslated Regions; D002352:Carrier Proteins; D017931:DNA Primers; D006360:Heat-Shock Proteins; D035683:MicroRNAs; C429767:TP53INP1 protein, human