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HOTAIR enhanced aggressive biological behaviors and induced radio-resistance via inhibiting p21 in cervical cancer

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Tumor Biology

Abstract

We previously reported the frequent overexpression of HOX Antisense Intergenic RNA (HOTAIR) in human cervical cancer, which was significantly correlated with tumor progression and poor prognosis. In the present study, we investigated the detailed biological functions of HOTAIR in cervical cancer. In vitro, upregulation of HOTAIR inhibited apoptosis and promoted cellular proliferation, cell cycle progression, migration, and invasion; on the contrast, downregulation of HOTAIR induced more apoptosis, suppressed cellular proliferation, cell cycle, migration, and invasion. Moreover, a high level of HOTAIR was notably associated with radio-resistance and downregulation of p21 in the primary cultured cervical cancer cells. Further, we demonstrated that elevated HOTAIR could induce radio-resistance via inhibiting p21 in HeLa cells, while knockdown of HOTAIR upregulated p21 and consequentially increased the radio-sensitivity of C33A cells. Consistently, stable knockdown of HOTAIR significantly suppressed tumor growth and sensitized cervical cancer to radiotherapy in vivo. In conclusion, HOTAIR served as an onco-lncRNA in cervical cancer which could enhance various aggressive biological behaviors. Moreover, we proved that HOTAIR execute its functions mainly through inhibiting the p21 expression. These results proposed that targeting HOTAIR might be a potent therapeutic strategy in cervical cancer, especially for those patients who accepted radiotherapy.

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Acknowledgments

Our study was supported by grants from the Scientific Bureau of Wuxi (CSE31N1418) and the Health Bureau of Wuxi (MS201417, FYKY201401) to Yuan Wang.

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Authors and Affiliations

  1. Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Li Jing

  2. Institute of Clinical Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China

    Li Jing & Qiu Haifeng

  3. Department of Obstetrics and Gynecology, The Affiliated Hospital of Jiangnan University and The 4th People’s Hospital of Wuxi, Wuxi, 214062, Jiangsu Province, China

    Wang Yuan, Dong Ruofan & Yu Jinjin

  4. Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, No. 1, East Jianshe Road, Erqi District, Zhengzhou, 450052, Henan Province, China

    Qiu Haifeng

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  1. Li Jing
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  2. Wang Yuan
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  3. Dong Ruofan
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  4. Yu Jinjin
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Correspondence to Qiu Haifeng.

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Jing, L., Yuan, W., Ruofan, D. et al. HOTAIR enhanced aggressive biological behaviors and induced radio-resistance via inhibiting p21 in cervical cancer. Tumor Biol. 36, 3611–3619 (2015). https://doi.org/10.1007/s13277-014-2998-2

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  • DOI: https://doi.org/10.1007/s13277-014-2998-2

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