Department of Endocrinology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210011, P.R. China.
Department of Endocrinology, Clinical Medical College of Yangzhou University, Yangzhou, Jiangsu 225001, P.R. China.
Oncol Rep. 2020 Oct;44(4):1489-1501. doi: 10.3892/or.2020.7712. Epub 2020 Aug 3.
It has been revealed from microarray data analysis that long intergenic non‑coding RNA 02454 (LINC02454) is highly expressed in papillary thyroid cancer (PTC). The aim of the present study was to explore the potential role of LINC02454 in the tumorigenesis of PTC. The mRNA expression levels of LINC02454 were assessed using data from The Cancer Genome Atlas (TCGA) and the GSE66783 cohort in thyroid cancer, and were validated using reverse transcription‑quantitative PCR in 104 patients with PTC recruited in the present study. The association between the LINC02454 mRNA expression levels and the clinicopathological features of the 104 patients with PTC were also analyzed. Functional enrichment analyses were conducted on the differentially expressed genes in the high and low LINC02454 expression groups that were identified from the TCGA cohort. RNA interference, using short interfering (si)RNA against LINC02454, was used to investigate the role of LINC02454 in the biological functions of PTC cells in vitro. The expression level of LINC02454 was significantly increased in PTC tissues (P=0.0011) and was significantly associated with a larger tumor size, T stage, an advanced TNM stage and an increased lymph node metastasis (P<0.05), which was consistent with that in the TCGA and GSE66783 cohort. High expression levels of LINC02454 were observed in patients with PTC that also had BRAF mutations (P<0.001), and were significantly associated with a poorer disease‑free survival in the TCGA cohort (P<0.05). Functional enrichment analysis indicated that LINC02454‑related genes were significantly enriched in Gene Ontology terms, such as 'positive regulation of cell proliferation', 'positive regulation of cell division' and 'cell adhesion', and the following Kyoto Encyclopedia of Genes and Genomes pathways: 'Pathways in cancer' 'proteoglycans in cancer' and 'ECM‑receptor interaction'. In vitro, the knockdown of LINC02454 markedly arrested the cells in the G0/G1 phase of the cell cycle, and also led to an overall increase in apoptosis, as well as to an unexpected decrease in cell proliferation. LINC02454 may thus potentially function as an oncogene, which inhibits the apoptosis and enhances proliferation of PTC cells. Thus, as suggested by the findings of the present study, LINC02454 may be used as a diagnostic and prognostic biomarker for PTC in the future.
从基因芯片数据分析中发现,长链非编码 RNA 02454(LINC02454)在甲状腺乳头状癌(PTC)中高表达。本研究旨在探讨 LINC02454 在 PTC 肿瘤发生中的潜在作用。使用来自癌症基因组图谱(TCGA)和甲状腺癌 GSE66783 队列的数据评估 LINC02454 的 mRNA 表达水平,并使用逆转录-定量 PCR 在本研究中招募的 104 例 PTC 患者中进行验证。还分析了 104 例 PTC 患者的 LINC02454 mRNA 表达水平与临床病理特征之间的相关性。对 TCGA 队列中高和低 LINC02454 表达组的差异表达基因进行功能富集分析。使用针对 LINC02454 的短发夹 RNA(siRNA)进行 RNA 干扰,以研究 LINC02454 在体外 PTC 细胞生物学功能中的作用。LINC02454 的表达水平在 PTC 组织中明显升高(P=0.0011),并且与较大的肿瘤大小、T 分期、较晚的 TNM 分期和增加的淋巴结转移显著相关(P<0.05),这与 TCGA 和 GSE66783 队列一致。在具有 BRAF 突变的 PTC 患者中观察到 LINC02454 的高表达(P<0.001),并且在 TCGA 队列中与无病生存时间显著相关(P<0.05)。功能富集分析表明,LINC02454 相关基因在基因本体论术语中显著富集,例如“细胞增殖的正调节”、“细胞分裂的正调节”和“细胞粘附”,以及以下京都基因与基因组百科全书途径:“癌症途径”、“癌症中的糖胺聚糖”和“ECM-受体相互作用”。在体外,LINC02454 的敲低显着使细胞停滞在细胞周期的 G0/G1 期,并且还导致整体凋亡增加,以及出乎意料的细胞增殖减少。因此,正如本研究结果所表明的那样,LINC02454 可能作为一种癌基因,抑制 PTC 细胞的凋亡并增强增殖。因此,正如本研究结果所表明的那样,LINC02454 可能在未来用作 PTC 的诊断和预后生物标志物。