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SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer

Oncogene volume 34, pages 5648–5661 (2015)Cite this article

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Abstract

The long noncoding RNA TINCR shows aberrant expression in human squamous carcinomas. However, its expression and function in gastric cancer remain unclear. We report that TINCR is strongly upregulated in human gastric carcinoma (GC), where it was found to contribute to oncogenesis and cancer progression. We also revealed that TINCR overexpression is induced by nuclear transcription factor SP1. Silencing TINCR expression inhibited cell proliferation, colony formation, tumorigenicity and apoptosis promotion, whereas TINCR overexpression promoted cell growth, as documented in the SGC7901 and BGC823 cell lines. Mechanistic analyses indicated that TINCR could bind to STAU1 (staufen1) protein, and influence KLF2 mRNA stability and expression, then KLF2 regulated cyclin-dependent kinase genes CDKN1A/P21 and CDKN2B/P15 transcription and expression, thereby affecting the proliferation and apoptosis of GC cells. Together, our findings suggest that TINCR contributes to the oncogenic potential of GC and may constitute a potential therapeutic target in this disease.

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Acknowledgements

We thank Dr Taniguchi (First Department of Internal Medicine, Sapporo Medical University School of Medicine, Sapporo, Japan) for the kind gift of KLF2-FLAG expression vector, Dr Wei-liang Xiong (Department of Biochemistry and The Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-Sen University) for the help of RNA pull down assay, and Professor Wei De and Dr Ming Sun (Department of Biochemistry and Molecular Biology, Nanjing Medical University) for the help of assay design. This study was supported by the National Natural Science Foundation of China (81172140, 81272532), Jiangsu Province Clinical Science and Technology projects (Clinical Research Center, BL2012008) and the Priority Academic Program Development of Jiangsu Higher Education Institutions (Public Health and Preventive Medicine, JX10231801).

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Authors and Affiliations

  1. Department of Oncology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, People’s Republic of China

    T-p Xu, R Xia, L Yin, W-m Chen & Y-q Shu

  2. Department of Gastrointestinal Surgery, Northern Jiangsu People's Hospital, Clinical Medical School, Yangzhou University, Yangzhou, People’s Republic of China

    X-x Liu

  3. Clinical Medical Examination Center, Northern Jiangsu People's Hospital, Clinical Medical School, Yangzhou University, Yangzhou, People’s Republic of China

    R Kong

  4. Department of Medical Oncology, Huai’an First People’s Hospital, Nanjing Medical University, Huai’an, People’s Republic of China

    M-d Huang

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Correspondence to Y-q Shu.

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Xu, Tp., Liu, Xx., Xia, R. et al. SP1-induced upregulation of the long noncoding RNA TINCR regulates cell proliferation and apoptosis by affecting KLF2 mRNA stability in gastric cancer. Oncogene 34, 5648–5661 (2015). https://doi.org/10.1038/onc.2015.18

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