Wu Guojun, Zhou Wenhong, Lin Xiaona, Sun Yongjie, Li Jiyu, Xu Hao, Shi Peng, 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;19:1153-1163. doi: 10.1016/j.omtn.2019.11.037. Epub 2020 Jan 15.
Circular RNAs (circRNAs) are a class of non-coding RNAs broadly expressed in cells of various species. However, the molecular mechanisms that link circRNAs with progression of papillary thyroid carcinoma (PTC) are not well understood. In the present study, we attempted to provide novel basis for targeted therapy for PTC from the aspect of circRNA-miRNA-mRNA interaction. We investigated the expression of circRNAs in five paired PTC tissues and normal tissues by microarray analysis. The circRNA microarray assay followed by qRT-PCR was used to verify the differential expression of hsa_circ_0059354, which is located on chromosome 20 and derived from RASSF2, and thus we named it circRASSF2. The qRT-PCR analysis was to investigate the expression pattern of circRASSF2 in PTC tissues and cell lines. Then the effects of circRASSF2 on cell proliferation and apoptosis were assessed in PTC in vitro. Furthermore, bioinformatics online programs predicted and luciferase reporter assays were used to validate the association of circRASSF2 and miR-1178 in PTC cells. In this study, circRASSF2 was observed to be upregulated in PTC tissues and cell lines. Knockdown of circRASSF2 inhibited cell proliferation and promoted cell apoptosis in PTC cells. Bioinformatics analysis predicted that there is a circRASSF2/miR-1178/TLR4 axis in PTC. A dual-luciferase reporter system validated the direct interaction of circRASSF2, miR-1178, and TLR4. Furthermore, circRASSF2 facilitates PTC progression in vivo. Importantly, we demonstrated that circRASSF2 was upregulated in serum exosomes from PTC patients. In summary, our study demonstrates that circRASSF2 modulates PTC progression through the miR-1178/TLR4 pathway. Our findings indicate that circRASSF2 may serve as a promising therapeutic target for the treatment of PTC patients.
环状RNA（circRNAs）是一类在各种物种的细胞中广泛表达的非编码RNA。然而，将circRNAs与甲状腺乳头状癌（PTC）进展联系起来的分子机制尚未完全清楚。在本研究中，我们试图从circRNA- miRNA- mRNA相互作用的角度为PTC的靶向治疗提供新的依据。我们通过微阵列分析研究了五个配对的PTC组织和正常组织中circRNAs的表达。采用circRNA微阵列分析结合qRT-PCR验证位于20号染色体上且来源于RASSF2的hsa_circ_0059354的差异表达，因此我们将其命名为circRASSF2。qRT-PCR分析旨在研究circRASSF2在PTC组织和细胞系中的表达模式。然后在体外评估circRASSF2对PTC细胞增殖和凋亡的影响。此外，利用生物信息学在线程序进行预测，并通过荧光素酶报告基因检测验证PTC细胞中circRASSF2与miR-1178的关联。在本研究中，观察到circRASSF2在PTC组织和细胞系中上调。敲低circRASSF2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circRASSF2/miR-1178/TLR4轴。双荧光素酶报告系统验证了circRASSF2、miR-1178和TLR4之间的直接相互作用。此外，circRASSF2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circRASSF2上调。总之，我们的研究表明circRASSF2通过miR-1178/TLR4途径调节PTC进展。我们的研究结果表明，circRASSF2可能是治疗PTC患者的一个有前景的治疗靶点。
