The important role played by circular RNA (circRNA) in promoting the progression of papillary thyroid cancer (PTC) is attracting ever more attention among medical researchers. However, what the precise contribution is of circRTN1 in PTC progression remains unclear. The study was designed to analyze the role and mechanism of circRTN1 in regulating PTC progression.
Human PTC cell lines (TPC-1 and IHH-4) and human thyroid normal cells (Nthy-ori 3-1) were used for in vitro assays. mRNA or protein expression of circRTN1, miR-101-3p, and high mobility group box 1 (HMGB1) were detected by quantitative real-time polymerase chain reaction or western blot. Cell proliferation was investigated by cell counting kit-8 assay, cell colony formation assay, and 5-ethynyl-2′-deoxyuridine assay. Wound-healing assay and transwell invasion assay were conducted to evaluate cell migration and invasion. Dual-luciferase reporter assay and RNA immunoprecipitation assay were applied to verify the target relations between circRTN1, miR-101-3p, and HMGB1. A xenograft tumor model was established to demonstrate the effect of circRTN1 on tumor formation in vivo. An immunohistochemistry assay was used to detect protein expression of HMGB1, ki-67, E-cadherin, and vimentin.
In comparison with healthy thyroid tissues and cells, PTC tissues and cells displayed high circRTN1 RNA expression and high HMGB1 mRNA and protein expression but low miR-101-3p expression. Silencing of circRTN1 suppressed PTC cell proliferation, migration, and invasion in vitro. MiR-101-3p was a target of circRTN1, and the knockdown of miR-101-3p relieved circRTN1 absence-mediated suppressive effects on PTC cell malignancy. HMGB1 was identified as a target gene of miR-101-3p, and overexpressed HMGB1 almost reverted the inhibitory impacts induced by miR-101-3p mimic in PTC cells. Moreover, circRTN1 silencing hampered tumor formation in vivo.
CircRTN1 depletion impeded PTC cell malignancy via the miR-101-3p/HMGB1 pathway, which provided a possible circRNA-targeted therapeutic strategy for PTC.
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This study was performed with the ratification of the Ethics Committee of The First People’s Hospital of Jingmen City, Hubei Province, People’s Republic of China
Written informed consent was signed by all participants.
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Supplementary materials 1:
Figure S1 CircRTN1 expression analysis in PTC cells. Barplot of circRTN1 expression in Nthy-ori 3-1 cells, FTC-133 cells, 8505C cells, TPC-1 cells and IHH-4 cells. Results are presented as mean ± SD. *P<0.05, **P<0.01 and ***P<0.001. Statistical analyses were performed using one-way ANOVA. Figure S2 The identification of target miRNAs of circRTN1 and target mRNAs of miR-101-3p. (A-B) Barplot of miR-1271-5p and miR-101-3p relative expression in TPC-1 cells and IHH-4 cells transfected with sh-NC or sh-circRTN1. Results are presented as mean ± SD. (C-D) Barplot of DNMT3A, CLDN1, ZEB1, VEGFA, LMO4, E2F3, YAP1, TRIM44, PDK4, MAPK1, KIF2A and HMGB1 expression in TPC-1 cells and IHH-4 cells transfected with miR-NC or miR-101-3p. Results are presented as mean ± SD. *P<0.05, **P<0.01 and ***P<0.001. Statistical analyses were performed using two-way ANOVA.
Supplementary materials 2:
Table S1 Relationship between circRTN1 expression and clinicopathologic features of papillary thyroid cancer patients. Table S2 The effects of circRTN1 knockdown on PTC cell migration and invasion.
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Zheng, M., Xu, L., Wei, C. et al. CircRTN1 stimulates HMGB1 to regulate the malignant progression of papillary thyroid cancer by sponging miR-101-3p. Hormones (2023). https://doi.org/10.1007/s42000-023-00440-y