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

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.

Keywords

long noncoding RNA / CRNDE / alternative splicing

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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).

Compliance with ethics guidelines

Xuefei Ma, Wei Zhang, Rong Zhang, Jingming Li, Shufen Li, Yunlin Ma, Wen Jin, and Kankan Wang declare that they have no conflict of interest. This article does not contain any studies with human or animal subjects.

Electronic Supplementary Material Supplementary material is available in the online version of this article at https://doi.org/10.1007/s11684-017-0557-0 and is accessible for authorized users.

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