School of Medicine and Health, Jiuzhou Polytechnic, Xuzhou, 221113, China.
Department of Oncology, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China.
Oncol Res. 2024 Oct 16;32(11):1747-1763. doi: 10.32604/or.2024.030945. eCollection 2024.
Papillary thyroid cancer (PTC) is the most prevalent histological type of differentiated thyroid malignancy. Circular RNAs (circRNAs) have been implicated in the pathogenesis and progression of various cancers. circTIAM1 (hsa_circ_0061406) is a novel circRNA with aberrant expression in PTC. However, its functional roles in PTC progression remain to be investigated.
The expression levels of circTIAM1 in the PTC and the matched para-cancerous tissues were detected by quantitative real-time reverse-transcription PCR (qRT-PCR). The subcellular localization of circTIAM1 was examined by fluorescence hybridization (FISH). Kaplan-Meier plot was used to analyze the association of clinicopathological features with circTIAM1 expression. Bioinformatics databases were utilized to predict the target miRNAs of circTIAM1 and the downstream target mRNAs. RNA pull-down, RIP assay, and dual-luciferase reporter assay were used to confirm the interactions. Functional experiments, such as CCK-8, EDU staining, and apoptosis assays, as well as xenograft model were employed to explore the impacts of circTIAM1, miR-338-3p, and LIM/SH3 protein 1 (LASP1) on the malignant phenotype of the PTC cells.
CircTIAM1 was highly expressed in PTC cells. Moreover, circTIAM1 silencing suppressed the proliferation and invasion of PTC cells and impaired tumorigenesis . Furthermore, miR-338-3p was verified as a miRNA target of circTIAM1. LASP1 was also identified as a downstream target of miR-338-3p. The anti-tumorigenic effect of miR-338-3p overexpression and the pro-tumorigenic effect of LASP1 was further explored by functional assays, which demonstrated that circTIAM1 modulated the PTC progression through targeting miR-338-3p/LASP1 axis.
The overexpression of circTIAM1 is associated with the malignant progression of PTC. A high level of circTIAM1 promotes the malignancy of PTC cells via the miR-338-3p/LASP1 axis.
甲状腺乳头状癌（PTC）是分化型甲状腺恶性肿瘤中最常见的组织学类型。环状 RNA（circRNA）与多种癌症的发病机制和进展有关。circTIAM1（hsa_circ_0061406）是一种新型 circRNA，在 PTC 中表达异常。然而，其在 PTC 进展中的功能作用仍有待研究。
采用实时定量逆转录 PCR（qRT-PCR）检测 PTC 及配对癌旁组织中 circTIAM1 的表达水平。采用荧光杂交（FISH）检测 circTIAM1 的亚细胞定位。Kaplan-Meier 图分析临床病理特征与 circTIAM1 表达的关系。利用生物信息学数据库预测 circTIAM1 的靶 miRNAs 和下游靶 mRNAs。采用 RNA 下拉、RIP 测定和双荧光素酶报告基因测定来验证相互作用。通过 CCK-8、EDU 染色和凋亡测定等功能实验以及异种移植模型来研究 circTIAM1、miR-338-3p 和 LIM/SH3 蛋白 1（LASP1）对 PTC 细胞恶性表型的影响。
circTIAM1 在 PTC 细胞中高表达。circTIAM1 沉默抑制 PTC 细胞的增殖和侵袭，抑制肿瘤发生。进一步证实 miR-338-3p 是 circTIAM1 的 miRNA 靶标。LASP1 也被鉴定为 miR-338-3p 的下游靶标。通过功能实验进一步探讨了 miR-338-3p 过表达的抗肿瘤作用和 LASP1 的促肿瘤作用，结果表明 circTIAM1 通过靶向 miR-338-3p/LASP1 轴调节 PTC 的进展。
circTIAM1 的过表达与 PTC 的恶性进展有关。高水平的 circTIAM1 通过 miR-338-3p/LASP1 轴促进 PTC 细胞的恶性转化。
