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

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.

替代剪接是一个严格调节的过程，有助于癌症的发展。 CRNDE是具有替代剪接的长期非编码RNA，与几种癌症的发病机理有关。但是，CRNDE的放松表达是否常见，哪些同工型主要与癌症有关。在这项研究中，我们报告说，在大多数固体和造血性恶性肿瘤中，Crnde异常表达。对正常样品中CRNDE表达的研究表明，CRNDE以组织和细胞特异性方式表达。从15种固体和造血肿瘤的2938例患者样品中CRNDE表达的进一步比较表明，CRNDE在111种恶性肿瘤中显着过表达，其中包括3种据报道和8种未报告，也暗示在各种癌症类型中过表达的同工型有所不同。此外，抗癌药物可以有效地抑制癌细胞和主要样品中的CRNDE过表达，甚至对CRNDE同工型的表达产生不同的影响。最后，12种剪接的同工型的实验曲线表明，剪接的变体CRNDE-G是多种癌症类型中最高表达的同工型。总的来说，我们的结果强调了CRNDE及其剪接的同工型的癌症相关特征，并可能为癌症诊断和治疗提供了有希望的靶标。