Wu Guojun, Zhou Wenhong, Pan Xiaohua, Sun Zhigang, Sun Yongjie, Xu Hao, Shi Peng, Li Jiyu, Gao Ling, Tian Xingsong
Department of Breast and Thyroid Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China; Department of Breast and Thyroid Surgery, Shandong Provincial ENT Hospital Affiliated to Shandong University, Jinan 250022, China.
Department of Nursing, Shandong Provincial Hospital Affiliated to Shandong University, Jinan 250021, China.
Mol Ther Nucleic Acids. 2020 Mar 6;19:1134-1144. doi: 10.1016/j.omtn.2019.12.025. Epub 2020 Jan 10.
Circular RNAs (circRNAs) are a class of noncoding RNAs that are broadly expressed in various biological cells and function in regulating gene expression. However, the molecular mechanisms that link circRNAs with progression of papillary thyroid carcinoma (PTC) are not well understood. In the present study, the function of circ_0006156 (circFNDC3B) was investigated in human PTC cells. First, we detected the expression of circFNDC3B in PTC tissues and PTC cell lines by RT-PCR. A luciferase reporter assay and AGO2-RNA immunoprecipitation (RIP) was used to confirm the relationship between circFNDC3B and microRNA (miR)-1178. PTC cells were stably transfected with small interfering RNA (siRNA) against circFNDC3B, and cell proliferation, migration, and invasion were detected to evaluate the effect of circFNDC3B in PTC, while tumorigenesis was assayed in nude mice. In this study, circFNDC3B was observed to be upregulated in PTC tissues and cell lines. Knockdown of circFNDC3B inhibited cell proliferation and promoted cell apoptosis in PTC cells. Bioinformatics analysis predicted that there is a circFNDC3B/miR-1178/Toll-like receptor 4 (TLR4) axis in PTC. The dual-luciferase reporter system validated the direct interaction of circFNDC3B, miR-1178, and TLR4. Furthermore, circFNDC3B facilitates PTC progression in vivo. Importantly, we demonstrated that circFNDC3B was upregulated in serum exosomes from PTC patients. In summary, our study demonstrated that circFNDC3B modulates PTC progression through the miR-1178/TLR4 pathway. Our findings indicated that circFNDC3B may serve as a promising therapeutic target for the treatment of PTC patients.
环状RNA(circRNAs)是一类非编码RNA,在各种生物细胞中广泛表达,并在调节基因表达中发挥作用。然而,circRNAs与甲状腺乳头状癌(PTC)进展之间的分子机制尚未完全阐明。在本研究中,我们对circ_0006156(circFNDC3B)在人PTC细胞中的功能进行了研究。首先,我们通过RT-PCR检测了circFNDC3B在PTC组织和PTC细胞系中的表达。采用荧光素酶报告基因检测和AGO2-RNA免疫沉淀(RIP)实验来证实circFNDC3B与微小RNA(miR)-1178之间的关系。用针对circFNDC3B的小干扰RNA(siRNA)稳定转染PTC细胞,检测细胞增殖、迁移和侵袭能力,以评估circFNDC3B在PTC中的作用,同时在裸鼠中检测其致瘤性。本研究中,circFNDC3B在PTC组织和细胞系中表达上调。敲低circFNDC3B可抑制PTC细胞的增殖并促进其凋亡。生物信息学分析预测PTC中存在circFNDC3B/miR-1178/Toll样受体4(TLR4)轴。双荧光素酶报告系统验证了circFNDC3B、miR-1178和TLR4之间的直接相互作用。此外,circFNDC3B在体内促进PTC进展。重要的是,我们证明了PTC患者血清外泌体中circFNDC3B上调。总之,我们的研究表明circFNDC3B通过miR-1178/TLR4途径调节PTC进展。我们的研究结果表明,circFNDC3B可能是治疗PTC患者的一个有前景的治疗靶点。