Abstract
HOTAIR is a long non-coding RNA that interacts with the polycomb repressive complex and suppresses its target genes. HOTAIR has also been demonstrated to promote malignancy. MicroRNA-141 (miR-141) has been reported to play a role in the epithelial to mesenchymal transition process, and the expression of miR-141 is inversely correlated with tumorigenicity and invasiveness in several human cancers. We found that HOTAIR expression is inversely correlated to miR-141 expression in renal carcinoma cells. HOTAIR promotes malignancy, including proliferation and invasion, whereas miR-141 suppresses malignancy in human cancer cells. miR-141 binds to HOTAIR in a sequence-specific manner and suppresses HOTAIR expression and functions, including proliferation and invasion. Both HOTAIR and miR-141 were associated with the immunoprecipitated Ago2 (Argonaute2) complex, and the Ago2 complex cleaved HOTAIR in the presence of miR-141. These results demonstrate that HOTAIR is suppressed by miR-141 in an Ago2-dependent manner.
Keywords:
Cancer Biology; Cell Growth; Gene Regulation; Genistein; HOTAIR; Invasion; Long Non-coding RNA; MicroRNA; Renal Carcinoma; miR-141.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, U.S. Gov't, Non-P.H.S.
MeSH terms
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Apoptosis / genetics
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Argonaute Proteins / genetics
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Argonaute Proteins / metabolism
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Base Sequence
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Binding Sites / genetics
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Blotting, Western
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Carcinoma, Renal Cell / genetics
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Carcinoma, Renal Cell / metabolism
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Carcinoma, Renal Cell / pathology
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Cell Line
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Cell Line, Tumor
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Cell Proliferation*
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Gene Expression Regulation, Neoplastic*
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HT29 Cells
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Homeodomain Proteins / genetics
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Homeodomain Proteins / metabolism
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Humans
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Kidney Neoplasms / genetics
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Kidney Neoplasms / metabolism
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Kidney Neoplasms / pathology
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MicroRNAs / genetics*
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MicroRNAs / metabolism
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Mutation
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Neoplasm Invasiveness
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Neoplasms / genetics
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Neoplasms / metabolism
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Neoplasms / pathology
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RNA Interference
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RNA, Long Noncoding / genetics*
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RNA, Long Noncoding / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Transcription Factors / genetics
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Transcription Factors / metabolism
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Zinc Finger E-box-Binding Homeobox 1
Substances
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AGO2 protein, human
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Argonaute Proteins
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HOTAIR long untranslated RNA, human
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Homeodomain Proteins
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MIRN141 microRNA, human
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MicroRNAs
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RNA, Long Noncoding
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Transcription Factors
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ZEB1 protein, human
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Zinc Finger E-box-Binding Homeobox 1