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CircTIAM1 overexpression promotes the progression of papillary thyroid cancer by regulating the miR-338-3p/LASP1 axis

YE ZHANG1, YANAN LIANG2, YAN WU2, LIWEN SONG2, ZUWANG ZHANG2,*
1 School of Medicine and Health, Jiuzhou Polytechnic, Xuzhou, 221113, China
2 Department of Oncology, University-Town Hospital of Chongqing Medical University, Chongqing, 401331, China
* Corresponding Author: ZUWANG ZHANG. Email: email

Oncology Research https://doi.org/10.32604/or.2024.030945

Received 04 May 2023; Accepted 01 November 2023; Published online 20 March 2024

Abstract

Background: 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. Methods: 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 in-situ 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 in vivo 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. Results: CircTIAM1 was highly expressed in PTC cells. Moreover, circTIAM1 silencing suppressed the proliferation and invasion of PTC cells in vitro and impaired tumorigenesis in vivo. 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. Conclusion: 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.

Keywords

Papillary thyroid cancer; CircRNAs; LASP1; CircTIAM1
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