Ding Xiaojie, Li Ruiqi, Xu Jingya, Hu Guangquan, Wang Wenping, Lv Qihuan, Wang Youmin
Department of Endocrinology, The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui 230022, P.R. China.
Department of Endocrinology, Anhui No. 2 Provincial People's Hospital, Hefei, Anhui 230041, P.R. China.
Oncol Lett. 2025 Feb 27;29(4):203. doi: 10.3892/ol.2025.14949. eCollection 2025 Apr.
Circular RNAs (circRNAs) are closely associated with human tumorigenesis; however, whether hsa_circ_0004846 serves a role in the progression of papillary thyroid carcinoma (PTC) remains unclear. Therefore, the present study aimed to investigate the effect of hsa_circ_0004846 on PTC. The results demonstrated that circ_0004846 was abnormally upregulated in PTC tissues and thyroid cancer cell lines (BCPAP, TPC-1 and IHH-4). Furthermore, hsa_circ_0004846-overexpressing or -depleted PTC cell lines (TPC-1 and IHH-4) were constructed using a lentiviral vector system. Notably, hsa_circ_0004846 overexpression markedly promoted cell proliferation, migration and invasion, as evidenced by activation of the PI3K/AKT pathway and the upregulation of vimentin, a class-III intermediate filament, which acts by regulating cell attachment and migration. However, hsa_circ_0004846 knockdown displayed the opposite effects. Mechanistically, the regulatory association among hsa_circ_0004846, microRNA (miR)-142-3p and Pellino E3 ubiquitin protein ligase 1 (PELI1) was validated using a dual-luciferase reporter assay. Specifically, the results demonstrated that hsa_circ_0004846 could sponge miR-142-3p, and the expression levels of miR-142-3p were negatively associated with those of hsa_circ_0004846. In addition, PELI1, a cancer-related E3 ubiquitin ligase, was identified as a downstream target of the hsa_circ_0004846/miR-142-3p axis in PTC. Therefore, PELI1 silencing could reverse the hsa_circ_0004846-induced malignant phenotype of PTC cells. Taken together, the results of the current study highlighted the effect of the hsa_circ_0004846/miR-142-3p/PELI1 regulatory network on PTC progression, thus providing a promising target for PTC treatment.
环状RNA（circRNAs）与人类肿瘤发生密切相关；然而，hsa_circ_0004846是否在甲状腺乳头状癌（PTC）进展中发挥作用仍不清楚。因此，本研究旨在探讨hsa_circ_0004846对PTC的影响。结果表明，circ_0004846在PTC组织和甲状腺癌细胞系（BCPAP、TPC-1和IHH-4）中异常上调。此外，使用慢病毒载体系统构建了hsa_circ_0004846过表达或缺失的PTC细胞系（TPC-1和IHH-4）。值得注意的是，hsa_circ_0004846过表达显著促进细胞增殖、迁移和侵袭，PI3K/AKT信号通路的激活以及波形蛋白（一种III类中间丝，通过调节细胞附着和迁移发挥作用）的上调证明了这一点。然而，hsa_circ_0004846敲低则表现出相反的效果。机制上，使用双荧光素酶报告基因检测验证了hsa_circ_0004846、微小RNA（miR）-142-3p和佩利诺E3泛素蛋白连接酶1（PELI1）之间的调控关系。具体而言，结果表明hsa_circ_0004846可以吸附miR-142-3p，且miR-142-3p的表达水平与hsa_circ_0004846的表达水平呈负相关。此外，PELI1是一种与癌症相关的E3泛素连接酶，被确定为PTC中hsa_circ_0004846/miR-142-3p轴的下游靶点。因此，PELI1沉默可逆转hsa_circ_0004846诱导的PTC细胞恶性表型。综上所述，本研究结果突出了hsa_circ_0004846/miR-142-3p/PELI1调控网络对PTC进展的影响，从而为PTC治疗提供了一个有前景的靶点。
