Department of General Surgery, Huzhou Central Hospital, Huzhou, China.
Cancer Med. 2018 Aug;7(8):3935-3944. doi: 10.1002/cam4.1627. Epub 2018 Jun 20.
Recently, a growing number of evidence has revealed that long noncoding RNAs (lncRNAs) act as key regulators in various cellular biologic processes, and dysregulation of lncRNAs involves in tumorigenesis and cancer progression. However, the expression pattern, clinical relevance, and biologic function of most lncRNAs in human thyroid cancer remain unclear. To identify more thyroid-cancer-associated lncRNAs, we analyzed the expression profile of lncRNAs in thyroid cancer tissues and adjacent normal or non-tumor tissues using RNA sequencing data and gene microarray data from The Cancer Genome Atlas and Gene Expression Omnibus. Annotation and analyses of these data revealed that hundreds of lncRNAs are differentially expressed in thyroid cancer tissues when compared with normal tissues. By copy number variation analyses, we identified that some of those dysregulated lncRNAs genome locus are accompanied with the copy number amplification or deletion. Moreover, some lncRNAs expression levels are significantly associated with thyroid cancer patients overall or recurrence-free survival time, such as RUNDC3A-AS1, FOXD2-AS1, PAX8-AS1, and CRYM-AS1. Furthermore, we validated an lncRNA termed LINC00704 in thyroid cancer cells by performing loss of function assays. Downregulation of LINC00704 could significantly impair thyroid cancer cells proliferation, colony formation, inhibit cell-cycle progression and cell invasion, and induce cell apoptosis. Taken together, our findings reveal that lots of lncRNAs are dysregulated and may play critical roles in thyroid cancer, and this study could provide useful resource for identification and investigation of novel lncRNA candidates for thyroid cancer.
最近，越来越多的证据表明，长链非编码 RNA（lncRNA）在各种细胞生物学过程中作为关键调节剂发挥作用，lncRNA 的失调涉及肿瘤发生和癌症进展。然而，人类甲状腺癌中大多数 lncRNA 的表达模式、临床相关性和生物学功能仍不清楚。为了鉴定更多与甲状腺癌相关的 lncRNA，我们使用来自癌症基因组图谱和基因表达综合数据库的 RNA 测序数据和基因芯片数据，分析了甲状腺癌组织和相邻正常或非肿瘤组织中 lncRNA 的表达谱。对这些数据的注释和分析表明，与正常组织相比，甲状腺癌组织中有数百个 lncRNA 表达差异。通过拷贝数变异分析，我们发现这些失调的 lncRNA 基因组位置中的一些伴随着拷贝数扩增或缺失。此外，一些 lncRNA 的表达水平与甲状腺癌患者的总生存率或无复发生存时间显著相关，例如 RUNDC3A-AS1、FOXD2-AS1、PAX8-AS1 和 CRYM-AS1。此外，我们通过进行功能丧失实验，在甲状腺癌细胞中验证了一个称为 LINC00704 的 lncRNA。下调 LINC00704 可显著损害甲状腺癌细胞的增殖、集落形成、抑制细胞周期进程和细胞侵袭，并诱导细胞凋亡。总之，我们的研究结果表明，大量的 lncRNA 失调，可能在甲状腺癌中发挥关键作用，本研究可为鉴定和研究甲状腺癌新型 lncRNA 候选物提供有用的资源。
