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Jiwen Yang, Yayin Huang, Bohan Dong, and Yunhai Dai

Objective: Considering the plight in thyroid cancer therapy, we aimed to find novel therapeutic targets from molecular perspective.

Methods: Quantitative real time polymerase chain reaction (qRT-PCR) and Western blot assay were carried out to determine RNA and protein expression. Cell counting kit-8 (CCK8) assay, flow cytometry, transwell migration assay and aerobic glycolysis analysis were performed to analyze cell proliferation, apoptosis, migration and aerobic glycolysis of thyroid cancer cells. MiRcode and Starbase software were used to search the downstream genes of long noncoding RNA (lncRNA) deleted in lymphocytic leukemia 2 (DLEU2) and microRNA-205-5p (miR-205-5p), and the intermolecular combination was confirmed by dual-luciferase reporter assay. The in vivo role of DLEU2 in tumor growth was verified using murine xenograft model.

Results: DLEU2 and tumor necrosis factor-α-induced protein 8 (TNFAIP8) were highly expressed in thyroid cancer tissues and cell lines. DLEU2 and TNRAIP8 promoted the proliferation, migration and aerobic glycolysis and restrained the apoptosis of thyroid cancer cells. DLEU2/miR-205-5p/TNFAIP8 signaling axis was identified in thyroid cancer cells. TNFAIP8 overexpression largely rescued the malignant phenotypes in DLEU2-silenced thyroid cancer cells. DLEU2 positively regulated TNFAIP8 expression through acting as miR-205-5p sponge in thyroid cancer cells. DLEU2 silencing blocked the growth of xenograft tumors in vivo.

Conclusion: lncRNA DLEU2 exerted a pro-tumor role to promote proliferation, migration and aerobic glycolysis while repress the apoptosis of thyroid cancer cells via miR-205-5p/TNFAIP8 axis.