Papillary Thyroid Cancer

DUXAP8[LncRNA]

miR-20b-5p[miRNA]

SOS1[mRNA]

Papillary thyroid carcinoma cells

Homo sapiens (human)

Oncol Rep. 2021 May;45(5):64. doi: 10.3892/or.2021.8015. Epub 2021 Mar 24.

lncRNA DUXAP8 inhibits papillary thyroid carcinoma cell apoptosis via sponging the miR-20b-5p/SOS1 axis.

qPCR;RT-qPCR;RIP assay;Western blot;Luciferase reporter assay;

Papillary thyroid carcinoma (PTC) is the most common type of cancer in the endocrine system. Long non-coding RNAs (lncRNAs) are associated with PTC progression. Therefore, the present study aimed to identify a novel lncRNA involved in PTC. Herein, dysregulated lncRNAs were analyzed in The Cancer Genome Atlas (TCGA)-thyroid cancer (THCA) data. Furthermore, the association between double homeobox A pseudogene 8 (DUXAP8) gene expression and disease stage, and prognosis of patients with PTC was evaluated using the GEPIA online database, while the correlation between DUXAP8 expression and the clinicopathological characteristics of patients with PTC was analyzed by Chi-square test. In addition, the biological effect of DUXAP8 expression on cell proliferation and apoptosis was also investigated. The protein and mRNA/microRNA (miRNA)/lncRNA expression levels were assessed by western blot analysis and reverse transcription-quantitative polymerase chain reaction (RT-qPCR), respectively. The interaction between miR-20b-5p and DUXAP8 was verified using bioinformatics analysis, RNA RIP assay, dual luciferase reporter assay, western blot analysis and RT-qPCR. The analysis of the TCGA-THCA data revealed that DUXAP8 was one of the most significantly upregulated lncRNAs in PTC. This finding was further confirmed in tissues from patients with PTC. Increased DUXAP8 expression was associated with higher grade and poorer prognosis in patients with PTC. In PTC cell lines, silencing of DUXAP8 expression with small interfering RNA-DUXAP8 (si-DUXAP8) induced cell apoptosis and attenuated cell proliferation. Additionally, transfection of PTC cells with si-DUXAP8 decreased the phosphorylation levels of MEK1/2 and ERK1/2, as well as downregulated the expression of son of sevenless 1 (SOS1), cyclin D1 (CCND1) and c-Myc. The results of the present study also revealed that miR-20b-5p could directly target DUXAP8. DUXAP8 expression was positively associated with that of SOS1, c-Myc and CCND1 in the TCGA-THCA data, and DUXAP8 level was positively correlated with that of SOS1 in PTC tumor tissues. Finally, transfection of PTC cells with the SOS1 overexpression plasmid, pcDNA3.1-SOS1, rescued the effects of si-DUXAP8 on cell proliferation and apoptosis. The present study was the first to identify DUXAP8 as a novel upregulated lncRNA in PTC, and provided new insights in understanding the effect of the lncRNA-miRNA-mRNA network in PTC.