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Identification of differential expressed lncRNAs in human thyroid cancer by a genome‐wide analyses

机译:通过全基因组分析鉴定人甲状腺癌中差异表达的lncRNA

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摘要

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 style="fixed-case">CRYM‐ style="fixed-case">AS1. Furthermore, we validated an lnc style="fixed-case">RNA termed style="fixed-case">LINC00704 in thyroid cancer cells by performing loss of function assays. Downregulation of style="fixed-case">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 lnc style="fixed-case">RNAs are dysregulated and may play critical roles in thyroid cancer, and this study could provide useful resource for identification and investigation of novel lnc style="fixed-case">RNA candidates for thyroid cancer.
机译:最近,越来越多的证据表明,长的非编码RNA(lncRNA)在各种细胞生物学过程中起着关键的调节作用,而lncRNA的失调则参与了肿瘤的发生和癌症的发展。然而,大多数lncRNA在人类甲状腺癌中的表达模式,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,我们使用了《癌症基因组图谱》和《基因表达综合》中的RNA测序数据和基因芯片数据,分析了lncRNA在甲状腺癌组织和邻近正常或非肿瘤组织中的表达谱。这些数据的注释和分析显示,与正常组织相比,数百种lncRNA在甲状腺癌组织中差异表达。通过拷贝数变异分析,我们确定了那些失调的lncRNAs基因组基因座中有一些伴随拷贝数扩增或缺失。此外,某些lncRNA的表达水平与甲状腺癌患者的总体生存时间或无复发生存时间显着相关,例如RUNDC3A‐AS1,FOXD2‐AS1,PAX8‐AS1和 style =“ fixed-case”> CRYM ‐ style =“ fixed-case”> AS 1。此外,我们通过执行功能丧失测定法验证了甲状腺癌细胞中称为 style =“ fixed-case”> LINC 00704的lnc style =“ fixed-case”> RNA 。 style =“ fixed-case”> LINC 00704的下调可能显着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。综上所述,我们的研究结果表明,许多lnc style =“ fixed-case”> RNA s失调并且可能在甲状腺癌中起关键作用,这项研究可为鉴定和研究新疾病提供有用的资源。 lnc style =“ fixed-case”> RNA 甲状腺癌候选者。

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