Circular RNA Pvt1 oncogene (CircPVT1) promotes the progression of papillary thyroid carcinoma by activating the Wnt/β-catenin signaling pathway and modulating the ratio of microRNA-195 (miR-195) to vascular endothelial growth factor A (VEGFA) expression

Abstract

Circular RNAs (circRNAs) have been reported to be involved in the progression of papillary thyroid carcinoma (PTC). However, the role of circular RNA Pvt1 oncogene ( circPVT1) in PTC has rarely been reported. In this study, we aimed to investigate the function and mechanism of circPVT1 in PTC. The expression level of circPVT1, miR-195 and VEGFA were determined by reverse transcription‑quantitative PCR (RT‑qPCR). Fisher’s exact test was used to analyze the correlation between circPVT1 expression and PTC clinical features. Cell Counting Kit-8 (CCK-8) and 5-Ethynyl-2ʹ-deoxyuridine (EdU) staining assay and transwell assay were conducted to evaluate the cell proliferation, migration and invasion ability. Dual-luciferase reporter and Western blot assay were conducted for evaluating the correlation between miR-195 and circPVT1 or VEGFA . The results of RT-PCR showed that the expression level of circPVT1 was significantly upregulated in PTC tissues and cell lines. After downregulating circPVT1 expression in PTC cells, the abilities of cell proliferation, migration, and invasion were obviously suppressed, and the Wnt/β-catenin signaling pathway was also repressed. Besides, miR-195 could both bind to PVT1 and VEGFA , while PVT1 could promote the expression of VEGFA by binding to miR-195 . Downregulation of VEGFA expression in PTC cells revealed weakened cell proliferation, migration, and invasion capacities, and restrained Wnt/β-catenin signaling pathway. Therefore, we demonstrated that circPVT1 could promote VEGFA expression by sponging miR-195. CircPVT1 could serve as a molecule sponge for miR-195 and mediate the ceRNA network to promote the expression of VEGFA , thus contributed to the malignant progression of PTC.

Long intergenic non-protein-coding RNA 467 promotes tumor progression and angiogenesis via the microRNA-128-3p/vascular endothelial growth factor C axis in colorectal cancer

“…Subsequently, the cells were fixed in 4% paraformaldehyde and stained with DAPI. Finally, cell counting was performed using fluorescence microscopy to quantify the percentage of EdU-positive cells [ 32 ].…”

Function and Clinical Significance of Circular RNAs in Thyroid Cancer

“…Studies have also revealed that different circRNAs contain the same type and miRNA binding sites that can specifically bind to miRNAs, thereby reducing miRNA activity and upregulating the expression of miRNA-related target genes (Shu et al, 2020;Luo et al, 2021), such as hsa_circ_0058124 and circUBAP2, which are revealed as miR-370-3p sponges and promote proliferation and invasion of TC cells (Liu L. et al, 2020;Xiong et al, 2021b). In addition, specific circRNAs protect homologous mRNAs from miRNA-mediated degradation by inhibiting miRNA activity (Zeng et al, 2021). For example, Zeng et al revealed that circPVT1 serves as a ceRNA to sequester miR-195 and promote the PVT1-mediated malignant progression in PTC (Zeng et al, 2021).…”

“…In addition, specific circRNAs protect homologous mRNAs from miRNA-mediated degradation by inhibiting miRNA activity (Zeng et al, 2021). For example, Zeng et al revealed that circPVT1 serves as a ceRNA to sequester miR-195 and promote the PVT1-mediated malignant progression in PTC (Zeng et al, 2021). Accumulating evidence has identified individual circRNAs containing multiple RBP motifs, suggesting circRNAs may sponging protein and modulate RBP-dependent functions (Bronisz et al, 2020;Tsitsipatis et al, 2021).…”

MicroRNAs as the critical regulators of cell migration and invasion in thyroid cancer

“… Diagnosis 60 patients 3 cell lines China 2016 Wang [ 86 ] miR-195 VEGFA CircPVT1 promoted the PTC cell migration by miR-195 sponging and subsequent VEGFA up regulation. Diagnosis 50 patients 4 cell lines China 2021 Zeng [ 87 ] miR-520a-3p JAK1 MiR-520a-3p inhibited the JAK-STAT signaling by JAK1 suppression which inhibited EMT and migration of PTC cells. Diagnosis 137 patients 6 cell lines China 2019 Bi [ 88 ] miR-361-5p ROCK1 MiR-361-5p inhibited PTC cells migration by ROCK1 targeting.…”

“…VEGFA is a tyrosine kinase receptor involved in angiogenesis. CircPVT1 promoted the PTC cell migration by miR-195 sponging and subsequent VEGFA up regulation [ 87 ]. Janus kinases (JAK) are a class of tyrosine kinases involved in cell growth, differentiation, and apoptosis.…”