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Overexpressed long noncoding RNA CRNDE with distinct alternatively spliced isoforms in multiple cancers

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Abstract

Alternative splicing is a tightly regulated process that contributes to cancer development. CRNDE is a long noncoding RNA with alternative splicing and is implicated in the pathogenesis of several cancers. However, whether deregulated expression of CRNDE is common and which isoforms are mainly involved in cancers remain unclear. In this study, we report that CRNDE is aberrantly expressed in the majority of solid and hematopoietic malignancies. The investigation of CRNDE expression in normal samples revealed that CRNDE was expressed in a tissue- and cell-specific manner. Further comparison of CRNDE expression in 2938 patient samples from 15 solid and hematopoietic tumors showed that CRNDE was significantly overexpressed in 11 malignancies, including 3 reported and 8 unreported, and also implicated that the overexpressed isoforms differed in various cancer types. Furthermore, anti-cancer drugs could efficiently repress CRNDE overexpression in cancer cell lines and primary samples, and even had different impacts on the expression of CRNDE isoforms. Finally, experimental profiles of 12 alternatively spliced isoforms demonstrated that the spliced variant CRNDE-g was the most highly expressed isoform in multiple cancer types. Collectively, our results emphasize the cancer-associated feature of CRNDE and its spliced isoforms, and may provide promising targets for cancer diagnosis and therapy.

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Acknowledgements

This work was supported in part by National Natural Science Foundation of China (Nos. 81530003, 81300403, 81770153 and 91440114), The National Key Research and Development Program (No. 2016YFC0902800), Shanghai Leading Talent Projects (No. 2015008) and the Academic Leader Program of Shanghai Science and Technology Committee (No. 2015137).

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  1. These authors contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Medical Genomics and Shanghai Institute of Hematology, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China

    Xuefei Ma, Wei Zhang, Jingming Li, Shufen Li, Yunlin Ma, Wen Jin & Kankan Wang

  2. School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai, 200240, China

    Wei Zhang & Kankan Wang

  3. Department of Hematology, Xi’an Gaoxin Hospital, Xi’an, 710075, China

    Rong Zhang

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  1. Xuefei Ma
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Ma, X., Zhang, W., Zhang, R. et al. Overexpressed long noncoding RNA CRNDE with distinct alternatively spliced isoforms in multiple cancers. Front. Med. 13, 330–343 (2019). https://doi.org/10.1007/s11684-017-0557-0

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