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

Yanqi Li, Jun Qin, Zhaocai He, Guang Cui, Kun Zhang, Buqiang Wu
Genes & Genomics 2021 January 22

BACKGROUND: 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.

OBJECTIVE: This study was performed to investigate the biological function and molecular mechanism of circPUM1 in PTC.

METHODS: 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.

RESULTS: 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.

CONCLUSION: 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.

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