Dai Lei, Zhang Weidong, Wang Yinchun, Yu Kejie, Le Qi, Wu Xianjiang
Department of Thyroid Surgery, Ningbo No.2 Hospital,No. 41 Xibei Street, Ningbo City 315000, Zhejiang Province, China.
iScience. 2023 Aug 9;26(9):107564. doi: 10.1016/j.isci.2023.107564. eCollection 2023 Sep 15.
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 and 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 , while the miR-34a-5p inhibitor reversed these effects. Additionally, circAGTPBP1 knockdown inhibited tumor growth . Our findings suggest that circAGTPBP1 may act as a tumor promoter and could be a potential therapeutic target for PTC.
环状RNA(circRNAs)的失调与甲状腺乳头状癌(PTC)的发生和发展有关。在本研究中,我们通过RNA测序,利用PTC组织和匹配的癌旁正常组织分析了失调的circRNA谱。我们进行了实验以研究circAGTPBP1在PTC进展中的生物学功能。我们发现circAGTPBP1在PTC组织和细胞系中上调,其表达与肿瘤大小、淋巴结转移和临床分期呈正相关。通过RNA测序和生物信息学分析,我们确定miR-34a-5p和NOTCH1是circAGTPBP1的下游靶点。在功能上,circAGTPBP1敲低显著抑制了PTC细胞系的迁移、侵袭和转移,而miR-34a-5p抑制剂逆转了这些作用。此外,circAGTPBP1敲低抑制了肿瘤生长。我们的研究结果表明,circAGTPBP1可能作为肿瘤促进因子,并且可能是PTC的潜在治疗靶点。