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circAGTPBP1 promotes the progression of papillary thyroid cancer through the notch pathway via the miR-34a-5p/notch1 axis

Lei Dai, Weidong Zhang, Yinchun Wang, Kejie Yu, Qi Le, Xianjiang Wu

2023iScience13 citationsDOIOpen Access PDF

Abstract

The dysregulation of circular RNAs (circRNAs) has been implicated in the development and progression of papillary thyroid cancer (PTC). In this study, we analyzed the dysregulated circRNA profile using PTC tissues and matched adjacent normal tissues by RNA-seq. We conducted in vitro and in vivo experiments to investigate the biological functions of circAGTPBP1 in PTC progression. We found that circAGTPBP1 was upregulated in PTC tissues and cell lines, and its expression was positively correlated with tumor size, lymph node metastasis, and clinical stage. Using RNA-seq and bioinformatic analysis, we identified miR-34a-5p and NOTCH1 as downstream targets of circAGTPBP1. Functionally, circAGTPBP1 knockdown significantly inhibited the migration, invasion, and metastasis of PTC cell lines in vitro , while the miR-34a-5p inhibitor reversed these effects. Additionally, circAGTPBP1 knockdown inhibited tumor growth in vivo . Our findings suggest that circAGTPBP1 may act as a tumor promoter and could be a potential therapeutic target for PTC.

Topics & Concepts

Gene knockdownCancer researchPapillary thyroid cancerIn vivoDownregulation and upregulationMetastasismicroRNAIn vitroTumor progressionCell growthThyroid cancerBiologyNotch signaling pathwayCancerCircular RNACell cultureChemistryCell biologyGeneSignal transductionGeneticsCircular RNAs in diseasesMicroRNA in disease regulationCancer-related molecular mechanisms research