Identification of Long stress-induced non-coding transcripts that have altered expression in cancer

Division of Experimental Pathology, Department of Laboratory Medicine and Pathology, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Genomics (Impact Factor: 2.28). 03/2010; 95(6):355-62. DOI: 10.1016/j.ygeno.2010.02.009
Source: PubMed


It has recently become clear that the transcriptional output of the human genome is far more abundant than previously anticipated, with the vast majority of transcripts not coding for protein. Utilizing whole-genome tiling arrays, we analyzed the transcription across the entire genome in both normal human bronchial epithelial cells (NHBE) and NHBE cells exposed to the tobacco carcinogen NNK. Our efforts focused on the characterization of non-coding transcripts that were greater than 300 nucleotides in length and whose expression was increased in response to NNK. We identified 12 Long Stress-Induced Non-coding Transcripts that we term LSINCTs. Northern blot analysis revealed that these transcripts were larger than predicted from the tiling array data. Quantitative real-time RT-PCR performed across a panel of normal cell lines indicates that these transcripts are more abundantly expressed in rapidly growing tissues or in tissues that are more prone to cellular stress. These transcripts that have increased expression after exposure to NNK also had increased expression in a number of lung cancer cell lines and also in many breast cancer cell lines. Collectively, our results identified a new class of long stress responsive non-coding transcripts, LSINCTs, which have increased expression in response to DNA damage induced by NNK. LSINCTs interestingly also have increased expression in a number of cancer-derived cell lines, indicating that the expression is increased in both, correlating cellular stress and cancer.

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Available from: David I Smith, Mar 06, 2015
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    • "Upon exposure to environmental stressors such as ultraviolet-B irradiation, viral infection and translational inhibitors, specific lncRNAs are expressed (Sonkoly, et al.,2005). More specifically, a group of large intergenic ncRNAs (lincRNAs) were found to be involved in response to DNA damage which was regulated by the p53 pathway (Silva, et al.,2010; Mizutani, et al.,2012; Zhang, et al.,2013). "
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    • "For example, Silva et al., 2010 analyzed transcription across the entire genome in both normal human bronchial epithelial cells (NHBE) and NHBE cells exposed to the tobacco carcinogen 4-(methylnitrosamino)-1-(3- pyridyl)-1-butanone (NNK). Twelve long stress-induced noncoding transcripts (LSINCTs) were identified (Silva et al., 2010). We then examined, for the first time, the lncRNA expression profiles in 16HBE-T cells and found that a small number of lncRNAs were abnormally expressed, with changes greater than 2.0-fold. "
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    • "lncRNAs are dysregulated in a number of human diseases, including several cancers and neurological disorders and show tissue-specific expression [36]. Several lncRNA have increased expression in a number of cancer cells [37]. Genotoxic stress-inducible nuclear lncRNA have been identified [38]. "
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