Mitotically associated long non-coding RNA is a tumor promoter in anaplastic thyroid cancer.
Mitotically associated long non-coding RNA is a tumor promoter in anaplastic thyroid cancer.
复制标题
有丝分裂相关的长非编码 RNA 是甲状腺未分化癌的肿瘤启动子。
DOI：
10.21037/atm-20-4530
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发表时间：
2020-10
影响因子：
--
通讯作者：
Wang YL
中科院分区：
文献类型：
--
作者：
Huang NS;Lei BW;Tan LC;Yu PC;Shi X;Wang Y;Ji QH;Wei WJ;Lu ZW;Wang YL
背景甲状腺未分化癌（ATC）是所有癌症中最致命的一种，其患者对传统疗法的反应通常很差。目前，长链非编码RNA（lncRNA）在ATC致癌中的作用尚不清楚。在这项研究中，我们分析了ATC的lncRNA表达谱，目的是确定治疗该疾病的潜在分子靶点。方法对3例ATC和2例正常甲状腺（NT）组织进行全基因组测序，分析ATC的lncRNA表达谱。原始数据以及保存在基因表达综合库（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和凋亡测定。进行基因本体（GO）和基因集富集分析（GSEA）以确定失调的途径。结果全基因组测序结果显示182个lncRNA在ATC中差异表达。与NT和乳头状甲状腺癌（PTC）相比，其中一种lncRNA，即有丝分裂相关长非编码RNA（MANCR; LINC 00704）在ATC细胞系和患者样本中显著过表达。MANCR缺失可明显抑制ATC细胞的增殖和侵袭，并诱导细胞凋亡。通过进一步分析转录组数据，我们鉴定了451个与MANCR共表达的基因。GO和GSEA结果显示，调控最高的通路与有丝分裂和细胞周期有关。结论MANCR是ATC的肿瘤启动子，其作用可能与细胞周期调控有关。由于MANCR在大多数正常组织中的表达是最小的，因此它可能成为未来ATC治疗的潜在靶点。
Background 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. Methods 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. Results Whole transcriptome sequencing revealed 182 lncRNAs to be differentially expressed in ATC. One of the lncRNAs, mitotically associated long non-coding RNA (MANCR; LINC00704), was significantly overexpressed in ATC cell lines and patient samples compared with NT and papillary thyroid cancer (PTC). MANCR 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 MANCR. GO and GSEA showed that the top dysregulated pathways were related to mitosis and cell cycle. Conclusions MANCR is a tumor promoter in ATC, and its role in carcinogenesis is possibly associated with cell cycle regulation. Because MANCR expression is minimal in most normal tissues, it may serve as a potential target in the future treatment of ATC.
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影响因子：
7.3
作者：
Gao J;Aksoy BA;Dogrusoz U;Dresdner G;Gross B;Sumer SO;Sun Y;Jacobsen A;Sinha R;Larsson E;Cerami E;Sander C;Schultz N
通讯作者：
Schultz N
影响因子：
--
作者：
Fei, Zheng-hua;Yu, Xiao-juan;Xie, Cong-ying
通讯作者：
Xie, Cong-ying
影响因子：
64.8
作者：
通讯作者：
--
影响因子：
5.6
作者：
Tracy KM;Tye CE;Page NA;Fritz AJ;Stein JL;Lian JB;Stein GS
通讯作者：
Stein GS
影响因子：
5.8
作者：
Nikiforova, MN;Kimura, ET;Nikiforov, YE
通讯作者：
Nikiforov, YE