Abstract
Background
Circular RNAs (circRNAs) have been identified as vital players in tumors, including papillary thyroid carcinoma (PTC). The purpose of this study is to explore the functions of circ_0059354 on PTC development.
Methods
Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the levels of circ_0059354, microRNA-766-3p (miR-766-3p) and ADP ribosylation factor guanine nucleotide exchange factor 1 (ARFGEF1). Cell Counting Kit-8 (CCK-8) assay and colony formation assay were proceeded for cell proliferation ability. Transwell assay was conducted for cell migration and invasion. Tube formation assay was employed to examine the angiogenesis ability. Flow cytometry analysis was adopted for cell apoptosis. Western blot assay was conducted for protein levels. Dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay were utilized to verify the relationships among circ_0059354, miR-766-3p and ARFGEF1. The murine xenograft model was constructed to analyze the function of circ_0059354 in vivo.
Results
Circ_0059354 level was abnormally increased in PTC tissues and cells. Functionally, circ_0059354 silencing suppressed cell proliferation, migration, invasion and angiogenesis and facilitated apoptosis in PTC cells. Circ_0059354 was identified to sponge miR-766-3p, which directly targeted ARFGEF1. Moreover, circ_0059354 directly targeted miR-766-3p to positively regulated ARFGEF1 expression. MiR-766-3p inhibition reversed circ_0059354 knockdown-mediated effect of PTC cell malignant behaviors. Overexpression of miR-766-3p restrained the malignant behaviors of PTC cells, whereas ARFGEF1 elevation reversed the effects. Additionally, circ_0059354 deficiency blocked tumor growth in vivo.
Conclusion
Circ_0059354 served as an oncogene in PTC progression through regulating miR-766-3p/ARFGEF1 axis.
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Data availability statement
The data used to support the findings of this study are available from the corresponding author upon request.
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ZL: Conceptualization; Project administration; Writing—original draft. JX and HG: Data curation; Formal analysis. JL: Investigation; Methodology. XY: Writing—review & editing; Methodology. JM: Supervision; Visualization; Validation.
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The animal study was approved by the Ethics Committee of Animal Research of the Second Affiliated Hospital of Xi’an Jiaotong University and performed according to the Guidelines for Care and Use of Laboratory Animals of “National Institutes of Health".
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The tissues samples were collected from the patients after written informed consents were offered by the participants and approval was obtained from the Ethics Committee of the Second Affiliated Hospital of Xi’an Jiaotong University.
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Li, Z., Xu, J., Guan, H. et al. Circ_0059354 aggravates the progression of papillary thyroid carcinoma by elevating ARFGEF1 through sponging miR-766-3p. J Endocrinol Invest 45, 825–836 (2022). https://doi.org/10.1007/s40618-021-01713-2
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DOI: https://doi.org/10.1007/s40618-021-01713-2