Department of Head and Neck Surgery, Fudan University Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Cancer Med. 2019 Jun;8(6):3105-3119. doi: 10.1002/cam4.2150. Epub 2019 May 1.
Long noncoding RNAs (lncRNAs) are known to be key regulators of numerous biological processes, and substantial evidence supports that abnormal lncRNA expression plays a significant role in tumorigenesis and tumor progression. However, the mechanism by which lncRNAs function in thyroid carcinoma are still unclear. To investigate the role of lncRNAs in the tumorigenesis of papillary thyroid carcinoma (PTC), we analyzed lncRNA data in The Cancer Genome Atlas RNA-Seq database. A comparison of lncRNAs in cancerous thyroid tissues and normal tissues revealed hundreds of differentially expressed lncRNAs. Of 7589 lncRNAs identified in 561 thyroid cancer cases (503 cancerous tissues and 58 normal tissues), the expression levels of 144 were found to be aberrant (|log2 fold change| >2 and adjusted P < 0.05). The top 10 lncRNAs with the most significant differences were LINC01977, RP11-363E7.4, RP3-483K16.4, RP11-547D24.1, RUNDC3A-AS1, AC093609.1, CTD-2008L17.2, HAGLROS, UNC5B-AS1, and LINC01354. In addition, CTD-2008L17.2, HAGLROS, AC093609.1, UNC5B-AS1, and RUNDC3A-AS1 were shown to play vital roles in determining the histological cancer type. Furthermore, RP11-547D24.1 and UNC5B-AS1 could distinguish patients with different stages of PTC. The lncRNA RP11-547D24.1 was validated by loss-of-function assays, revealing that downregulation of this lncRNA regulates thyroid tumor cell proliferation and apoptosis, invasion, and migration. This study demonstrates the potential for using lncRNAs to interpret the pathogenesis and development of PTC.
长链非编码 RNA(lncRNA)是许多生物过程的关键调节剂,大量证据表明异常的 lncRNA 表达在肿瘤发生和肿瘤进展中起着重要作用。然而,lncRNA 在甲状腺癌中的作用机制尚不清楚。为了研究 lncRNA 在甲状腺乳头状癌(PTC)发生中的作用,我们分析了 The Cancer Genome Atlas RNA-Seq 数据库中的 lncRNA 数据。比较癌性甲状腺组织和正常组织中的 lncRNA,发现了数百个差异表达的 lncRNA。在 561 例甲状腺癌病例(503 例癌组织和 58 例正常组织)中鉴定出的 7589 个 lncRNA 中,发现 144 个表达异常(|log2 倍变化|>2,调整后 P<0.05)。差异最显著的前 10 个 lncRNA 分别为 LINC01977、RP11-363E7.4、RP3-483K16.4、RP11-547D24.1、RUNDC3A-AS1、AC093609.1、CTD-2008L17.2、HAGLROS、UNC5B-AS1 和 LINC01354。此外,CTD-2008L17.2、HAGLROS、AC093609.1、UNC5B-AS1 和 RUNDC3A-AS1 被证明在确定组织学癌症类型方面发挥着重要作用。此外,RP11-547D24.1 和 UNC5B-AS1 可以区分 PTC 不同阶段的患者。通过功能丧失实验验证了 lncRNA RP11-547D24.1,结果表明下调该 lncRNA 可调节甲状腺肿瘤细胞的增殖和凋亡、侵袭和迁移。本研究表明,lncRNA 具有解释 PTC 发病机制和发展的潜力。