Knockdown of circPUM1 impedes cell growth, metastasis and glycolysis of papillary thyroid cancer via enhancing MAPK1 expression by serving as the sponge of miR-21-5p.

Abstract

Circular RNAs (circRNAs) are a crucial class of regulatory RNAs in cancer procession, including papillary thyroid cancer (PTC). Circ-Pumilio 1 (circPUM1) is a novel circRNA with the oncogenic function in ovarian cancer and lung cancer. However, the role of circPUM1 in PTC is undiscovered. This study was performed to investigate the biological function and molecular mechanism of circPUM1 in PTC. CircPUM1 and microRNA-21-5p (miR-21-5p) levels were analyzed via quantitative real-time polymerase chain reaction (qRT-PCR). Cellular viability and metastasis were measured using Cell Counting Kit 8 (CCK-8) and transwell migration/invasion assay. Glycolysis was evaluated by glucose uptake and lactate production. Associated proteins were examined applying with western blot. Dual-luciferase reporter assay and RNA pull-down assay were used to analyze the interaction between circPUM1 or mitogen-activated protein kinase 1 (MAPK1) and miR-21-5p. Moreover, the role of circPUM1 in vivo was explored by xenograft tumor experiment. Significantly, circPUM1 was upregulated in PTC tissue samples and cells. Cell growth, metastasis and glycolytic process of PTC cells were all inhibited after downregulation of circPUM1. Besides, circPUM1 could sponge miR-21-5p and MAPK1 was a target gene of miR-21-5p. Furthermore, we found that the anti-cancer effect of circPUM1 knockdown on PTC was partly ascribed to MAPK1 downregulation by upregulating miR-21-5p. Silencing circPUM1 also impeded tumorigenesis of PTC in vivo via miR-21-5p/MAPK1 axis. These findings suggested that circPUM1 knockdown inhibited MAPK1 expression by targeting miR-21-5p, consequently leading to the repressive effect on PTC progression. CircPUM1 might be a promising target to improve the diagnosis and treatment of PTC.