Du Yaying, Xia Wenfei, Zhang Jinjun, Wan Dongyi, Yang Zhifang, Li Xingrui
Department of Thyroid and Breast Surgery, Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430030, P. R. China.
Mol Biosyst. 2017 Sep 26;13(10):2107-2115. doi: 10.1039/c7mb00375g.
Novel molecular-targeted treatments show great prospects for radioiodine-refractory and surgically inoperable thyroid carcinomas. While aberrations in protein-coding genes are a focus in molecular thyroid cancer medicine, the impact of oncogenes on the expression of long noncoding RNAs (lncRNAs) has been largely uncharacterized. We aimed to identify the expression patterns of lncRNAs and mRNAs in high-throughput molecular profiles of 18 papillary thyroid cancer (PTC) patients. We identified 452 mRNAs and 240 unannotated lncRNAs that were differentially expressed in PTC. Significantly enriched GO terms and pathways were identified, many of which were linked to cancer. By integrating the predicted lncRNA target genes with differentially expressed mRNAs, we identified 20 candidate lncRNAs in 45 PTC patients. Five lncRNAs (CTD-3193O13.11, RP5-1024C24.1, AC007255.8, HOXD-AS1, and RP11-402L6.1) were verified to be differentially expressed in PTC and to exhibit specific topological characteristics in the lncRNA-mRNA co-expression network. LncRNA CTD-3193O13.11 was determined to comprise a node of co-regulation with the other lncRNAs in PTC tumorigenesis. LncRNA RP5-1024C24.1, AC007255.8, and HOXD-AS1 expression was significantly related to clinical stage, lncRNA RP11-402L6.1 expression was associated with lymph node metastasis, lncRNA CTD-3193O13.11 expression was proportional to tumor size, and lncRNA AC007255.8 expression was proportional to patient age. Therefore, our study provides a genome-wide screening and analysis of lncRNA expression in PTC, which brings novel insights into the roles of lncRNAs in PTC progression.
新型分子靶向治疗在放射性碘难治性和手术不可切除的甲状腺癌中显示出巨大前景。虽然蛋白质编码基因的畸变是分子甲状腺癌医学的一个重点，但癌基因对长链非编码RNA（lncRNA）表达的影响在很大程度上尚未得到充分研究。我们旨在确定18例乳头状甲状腺癌（PTC）患者高通量分子图谱中lncRNA和mRNA的表达模式。我们鉴定出452种mRNA和240种未注释的lncRNA在PTC中差异表达。确定了显著富集的GO术语和通路，其中许多与癌症相关。通过将预测的lncRNA靶基因与差异表达的mRNA整合，我们在45例PTC患者中鉴定出20种候选lncRNA。五种lncRNA（CTD-3193O13.11、RP5-1024C24.1、AC007255.8、HOXD-AS1和RP11-402L6.1）被证实在PTC中差异表达，并在lncRNA-mRNA共表达网络中表现出特定的拓扑特征。lncRNA CTD-3193O13.11被确定为在PTC肿瘤发生过程中与其他lncRNA共同调节的一个节点。lncRNA RP5-1024C24.1、AC007255.8和HOXD-AS1的表达与临床分期显著相关，lncRNA RP11-402L6.1的表达与淋巴结转移相关，lncRNA CTD-3193O13.11的表达与肿瘤大小成正比，lncRNA AC007255.8的表达与患者年龄成正比。因此，我们的研究提供了PTC中lncRNA表达的全基因组筛选和分析，为lncRNA在PTC进展中的作用带来了新的见解。
