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Differential expression of long non-coding RNAs during genotoxic stress-induced apoptosis in HeLa and MCF-7 cells

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Abstract

Long non-coding RNAs (lncRNAs) are emerging as new players in cancer as they are implicated in diverse biological processes and aberrantly expressed in a variety of human cancers. No data are available on their function under genotoxic stress-induced apoptosis. In this work, we assessed the behavior of some candidate lncRNAs (HOTAIR, MALAT1, TUG1, lincRNA-p21, GAS5, MEG3, PANDA, UCA1, ANRIL, and CCND1) during DNA damage-induced cell death in HeLa and caspase-3-deficient MCF-7 cells using bleomycin (BLM) and γ-radiation to induce DNA damage. Cells were incubated in the presence of BLM for 24 h or irradiated. Apoptosis was analyzed by measurement of oligonucleosomal fragmentation of nuclear DNA. Our results reveal that basal RNA expression levels as well as the changes in the lncRNA expression rates during genotoxic stress-induced apoptosis were cell-type and/or DNA-damaging agent-specific. Generally, we found that some of the RNA molecules (HOTAIR and MALAT1) are down-regulated while many of them (lincRNA-p21, GAS5, MEG3, ANRIL, and ncRNA-CCND1) are up-regulated and some others (TUG1, UCA1, and PANDA) not affected. The decline in the expression of HOTAIR (approx. twofold, p < 0.01) and MALAT1 (approx 1.6-fold, p < 0.01) was clearly evident in BLM-treated HeLa and MCF cells (only HOTAIR, fivefold, p < 0.01). For lincRNA-p21, ncRNA-CCND1, and MEG3, a similar up-regulation pattern was obvious in both cell lines where the increase was generally more pronounced in BLM-treated cells. Interestingly, the induction of ANRIL and GAS5 was mainly restricted to irradiated cells. In conclusion, our findings reveal a differential regulation of individual lncRNAs during genotoxic stress-induced apoptosis.

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Acknowledgments

This work was supported by Istanbul University Research Fund (Projects # 4033 and 12527) and is part of the M.Sc. thesis of Emre Özgür.

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Authors and Affiliations

  1. Department of Basic Oncology, Institute of Oncology, Istanbul University, 34390 Capa, Istanbul, Turkey

    Emre Özgür, Ufuk Mert, Mustafa Isin, Nejat Dalay & Ugur Gezer

  2. Department of Radiation Physics, Institute of Oncology, Istanbul University, 34390 Capa, Istanbul, Turkey

    Murat Okutan

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  1. Emre Özgür
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  2. Ufuk Mert
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  3. Mustafa Isin
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  4. Murat Okutan
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  6. Ugur Gezer
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Correspondence to Ugur Gezer.

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Özgür, E., Mert, U., Isin, M. et al. Differential expression of long non-coding RNAs during genotoxic stress-induced apoptosis in HeLa and MCF-7 cells. Clin Exp Med 13, 119–126 (2013). https://doi.org/10.1007/s10238-012-0181-x

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  • DOI: https://doi.org/10.1007/s10238-012-0181-x

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