Han Pengli, Chen Guo, Zhang Qingsong, Shen Wenliang, Li Mingchuang, Lv Jing
Department of translational Medical Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, China.
Department of Thyroid Surgery, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China.
J Biochem Mol Toxicol. 2025 Aug;39(8):e70402. doi: 10.1002/jbt.70402.
CircRNAs can be applied as tumor biomarkers and potential therapeutic targets. Nevertheless, the function of circ_PSD3 in papillary thyroid carcinoma (PTC) has not been thoroughly explored. The current project attempts to analyze it. RT-qPCR was adopted for measuring the expression of circ_PSD3, HMGB3, miR-145-5p as well as miR-338-3p in PTC tissues and cells. Through performing cell counting kit-8 and transwell experiments, the biological effects of circ_PSD3, HMGB3, miR-145-5p and miR-338-3p on PTC cells were detected. Besides, a dual-luciferase reporter gene was employed to identify the underlying mechanism of circ_PSD3. The Western blot analysis assay was utilized to assess the expression levels of molecular marker proteins associated with epithelial-mesenchymal transition. According to the results, the expressions of circ_PSD3 and HMGB3 showed obvious upregulation in PTC tissues, whereas knockdown of circ_PSD3 or HMGB3 notably hindered cell proliferation, migration as well as invasion in PTC. Mechanistically, it could be discovered that miR-145-5p and miR-338-3p served as the targets of circ_PSD3, and HMGB3 was a target of miR-145-5p and miR-338-3p. Moreover, miR-145-5p and miR-338-3p were discovered to play the role of tumor suppressors in PTC. More importantly, the findings showed that cell proliferation, migration, invasion together with EMT processes were attenuated by circ_PSD3 knockdown, but partially counteracted by miR-338-3p (miR-145-5p) inhibitor or HMGB3 overexpression. Based on the obtained data, circ_PSD3 promotes PTC cell proliferation, migration, invasion and EMT by regulating the miR-145-5p/miR-338-3p/HMGB3 axis. The current work revealed the mechanism of action of circ_PSD3 in PTC and may play the role of a new medical target for PTC.
环状RNA（circRNAs）可作为肿瘤生物标志物和潜在的治疗靶点。然而，环状PSD3（circ_PSD3）在甲状腺乳头状癌（PTC）中的功能尚未得到充分研究。当前项目试图对其进行分析。采用逆转录-定量聚合酶链反应（RT-qPCR）检测circ_PSD3、高迁移率族蛋白B3（HMGB3）、微小RNA-145-5p（miR-145-5p）以及miR-338-3p在PTC组织和细胞中的表达。通过进行细胞计数试剂盒-8（CCK-8）和Transwell实验，检测circ_PSD3、HMGB3、miR-145-5p和miR-338-3p对PTC细胞的生物学作用。此外，采用双荧光素酶报告基因来确定circ_PSD3的潜在作用机制。利用蛋白质免疫印迹分析检测与上皮-间质转化相关的分子标志物蛋白的表达水平。结果显示，circ_PSD3和HMGB3在PTC组织中的表达明显上调，而敲低circ_PSD3或HMGB3显著抑制PTC细胞的增殖、迁移和侵袭。机制上，发现miR-145-5p和miR-338-3p是circ_PSD3的靶点，HMGB3是miR-145-5p和miR-338-3p的靶点。此外，发现miR-145-5p和miR-338-3p在PTC中发挥肿瘤抑制作用。更重要的是，研究结果表明，敲低circ_PSD3可减弱细胞增殖、迁移、侵袭以及上皮-间质转化过程，但miR-338-3p（miR-145-5p）抑制剂或HMGB3过表达可部分抵消这种作用。基于所获得的数据，circ_PSD3通过调节miR-145-5p/miR-338-3p/HMGB3轴促进PTC细胞的增殖、迁移、侵袭和上皮-间质转化。当前研究揭示了circ_PSD3在PTC中的作用机制，可能成为PTC的一个新的医学靶点。
