Abstract
Several noncoding RNAs do vital cellular functions, including gene regulation and cell differentiation. Previously, we reported that vault RNA (vRNA) has the ability to recognize chemotherapeutic compounds, such as mitoxantrone, based on biophysical and biochemical analyses. In the present study, we show that human glioblastoma-, leukemia-, and osteocarcinoma-derived cell lines overexpress vRNA and exhibit higher resistance toward mitoxantrone. Interestingly, when vRNA expression was suppressed by RNA interference in these cells, the resistance progressively decreased. In agreement with these findings, overexpression of vRNA-1 caused resistance to mitoxantrone. These results suggest a role of vRNA in mitoxantrone resistance in malignant cells and justify further studies on the importance and application of noncoding RNAs in cancer chemotherapeutics.
©2010 AACR.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antineoplastic Agents / pharmacology
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Base Sequence
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Bone Neoplasms / drug therapy
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Bone Neoplasms / genetics
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Cell Line, Tumor
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Drug Resistance, Neoplasm
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Gene Expression Regulation, Neoplastic
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Glioblastoma / drug therapy
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Glioblastoma / genetics
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Humans
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Leukemia / drug therapy
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Leukemia / genetics
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Mitoxantrone / pharmacology*
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Molecular Sequence Data
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Osteosarcoma / drug therapy
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Osteosarcoma / genetics
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RNA Interference
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RNA, Small Interfering / genetics
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RNA, Untranslated / biosynthesis*
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RNA, Untranslated / genetics*
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RNA, Untranslated / metabolism
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U937 Cells
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Vault Ribonucleoprotein Particles / biosynthesis*
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Vault Ribonucleoprotein Particles / genetics*
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Vault Ribonucleoprotein Particles / metabolism
Substances
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Antineoplastic Agents
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RNA, Small Interfering
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RNA, Untranslated
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Vault Ribonucleoprotein Particles
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Mitoxantrone