Huang Nai-Si, Lei Bo-Wen, Tan Li-Cheng, Yu Peng-Cheng, Shi Xiao, Wang Yu, Ji Qing-Hai, Wei Wen-Jun, Lu Zhong-Wu, Wang Yu-Long
Department of Head and Neck Surgery, Fudan University, Shanghai Cancer Center, Shanghai, China.
Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China.
Ann Transl Med. 2020 Oct;8(19):1226. doi: 10.21037/atm-20-4530.
Patients with anaplastic thyroid cancer (ATC), which is among the deadliest of all cancers, often have a poor response to traditional therapies. Currently, the role of long non-coding RNAs (lncRNAs) in ATC carcinogenesis is unclear. In this study, we analyzed the lncRNA expression profile of ATC with the aim of identifying potential molecular targets for treatment of the disease.
Whole transcriptome sequencing of three ATC and two normal thyroid (NT) samples was performed, and the lncRNA expression profile of ATC was analyzed. Original data as well as datasets deposited in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) were used for clinical validation. Cell proliferation, Transwell, and apoptosis assays were performed using ATC cell lines. Gene Ontology (GO) and gene set enrichment analyses (GSEA) were performed to determine the dysregulated pathways.
Whole transcriptome sequencing revealed 182 lncRNAs to be differentially expressed in ATC. One of the lncRNAs, mitotically associated long non-coding RNA (; LINC00704), was significantly overexpressed in ATC cell lines and patient samples compared with NT and papillary thyroid cancer (PTC). depletion in ATC cells significantly inhibited cancer cell proliferation and invasion, and induced apoptosis. By further analyzing the transcriptome data, we identified 451 genes co-expressed with . GO and GSEA showed that the top dysregulated pathways were related to mitosis and cell cycle.
is a tumor promoter in ATC, and its role in carcinogenesis is possibly associated with cell cycle regulation. Because expression is minimal in most normal tissues, it may serve as a potential target in the future treatment of ATC.
间变性甲状腺癌（ATC）是所有癌症中致死率最高的癌症之一，患者对传统疗法的反应通常较差。目前，长链非编码RNA（lncRNA）在ATC致癌过程中的作用尚不清楚。在本研究中，我们分析了ATC的lncRNA表达谱，旨在确定该疾病治疗的潜在分子靶点。
对三个ATC样本和两个正常甲状腺（NT）样本进行全转录组测序，并分析ATC的lncRNA表达谱。原始数据以及存于基因表达综合数据库（GEO）和癌症基因组图谱（TCGA）中的数据集用于临床验证。使用ATC细胞系进行细胞增殖、Transwell和凋亡检测。进行基因本体论（GO）和基因集富集分析（GSEA）以确定失调的通路。
全转录组测序显示182个lncRNA在ATC中差异表达。其中一个lncRNA，有丝分裂相关长链非编码RNA（；LINC00704），与NT和乳头状甲状腺癌（PTC）相比，在ATC细胞系和患者样本中显著高表达。ATC细胞中该lncRNA的缺失显著抑制癌细胞增殖和侵袭，并诱导凋亡。通过进一步分析转录组数据，我们鉴定出451个与该lncRNA共表达的基因。GO和GSEA显示，失调最严重的通路与有丝分裂和细胞周期有关。
该lncRNA是ATC中的肿瘤促进因子，其在致癌过程中的作用可能与细胞周期调控有关。由于该lncRNA在大多数正常组织中表达极少，它可能成为未来ATC治疗的潜在靶点。
