Upregulated CircRAD18 Promotes Tumor Progression by Reprogramming Glucose Metabolism in Papillary Thyroid Cancer
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Background: By regulating complex functional processes, circRNAs are crucial in the development of different cancers. Nevertheless, most circRNAs in papillary thyroid cancer metabolic reprogramming remain unknown.
Methods: The expression of circRNA was assessed by qRT-PCR in papillary thyroid cancer tissues and cell lines. Cell proliferation and glucose intake experiments were performed by certain kit. Transwell assays and wound healing assays were performed to investigate the function of circRNA in metastasis. In addition, a serious of molecular experiments were conducted to determine the exact mechanism of circRAD18. Luciferase reporter and RNA immunoprecipitation assay were conducted to determine the molecular interaction between circRNA and miRNA.
Results: We characterized circRAD18 as a significantly upregulated circRNA in papillary thyroid tissues and cell lines and found its downregulation could inhibit the growth and metastasis ability of papillary thyroid cancer. Interestingly, we found that circRAD18 was involved in glucose metabolism reprogramming of papillary thyroid cancer, and its silence could remarkably inhibit cell glucose uptake and lactate production in papillary thyroid cancer cells. Inhibition of circRAD18 could decrease the expression level of PDK1 protein by sponging miR-516b.
Conclusions: This study verified the novel function of the circRAD18-miR-516b-PDK1 axis in papillary thyroid cancer metabolic reprogramming progression, which has potential to be a novel therapeutic target.
Reprogramming of Thyroid Cancer Metabolism: from Mechanism to Therapeutic Strategy.
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