Institute for Digestive Research, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Department of Gastroenterology, Academy of Medicine, Lithuanian University of Health Sciences, Kaunas, Lithuania.
PLoS One. 2018 Dec 17;13(12):e0209342. doi: 10.1371/journal.pone.0209342. eCollection 2018.
Long intergenic non-coding RNAs (lincRNAs) are >200 nucleotides long non-coding RNAs, which have been shown to be implicated in carcinogenic processes by interacting with cancer associated genes or other non-coding RNAs. However, their role in development of rare gastrointestinal stromal tumors (GISTs) is barely investigated. Therefore, the aim of this study was to define lincRNAs deregulated in GIST and find new GIST-lincRNA associations. Next-generation sequencing data of paired GIST and adjacent tissue samples from 15 patients were subjected to a web-based lincRNA analysis. Three deregulated lincRNAs (MALAT1, H19 and FENDRR; adjusted p-value < 0.05) were selected for expression validation in a larger group of patients (n = 22) by RT-qPCR method. However, only H19 and FENDRR showed significant upregulation in the validation cohort (adjusted p < 0.05). Further, we performed correlation analyses between expression levels of deregulated lincRNAs and GIST-associated oncogenes or GIST deregulated microRNAs. We found high positive correlations between expression of H19 and known GIST related oncogene ETV1, and between H19 and miR-455-3p. These findings expand the knowledge on lincRNAs deregulated in GIST and may be an important resource for the future studies investigating lincRNAs functionally relevant to GIST carcinogenesis.
长链非编码 RNA（lncRNA）是长度超过 200 个核苷酸的非编码 RNA，已被证明通过与癌症相关基因或其他非编码 RNA 相互作用参与致癌过程。然而，它们在罕见胃肠道间质瘤（GIST）的发生发展中的作用尚未得到充分研究。因此，本研究旨在确定 GIST 中失调的 lincRNA，并寻找新的 GIST-lincRNA 关联。对 15 名患者配对的 GIST 和相邻组织样本的下一代测序数据进行了基于网络的 lincRNA 分析。选择了 3 个失调的 lincRNA（MALAT1、H19 和 FENDRR；调整后的 p 值<0.05），通过 RT-qPCR 方法在更大的患者组（n=22）中进行表达验证。然而，只有 H19 和 FENDRR 在验证队列中表现出显著上调（调整后的 p<0.05）。此外，我们还进行了失调 lincRNA 的表达水平与 GIST 相关癌基因或 GIST 失调 microRNA 之间的相关性分析。我们发现 H19 的表达与已知的 GIST 相关癌基因 ETV1 之间存在高度正相关，与 H19 和 miR-455-3p 之间也存在高度正相关。这些发现扩展了 GIST 中失调的 lincRNA 的知识，可能是未来研究 GIST 致癌功能相关 lincRNA 的重要资源。
