Tian-Zhao Du, Yang Yang, Xing-Xuan Wang, Yu-Xin Che, Xue-Lian Wang
Department of Microbiology and Parasitology, China Medical University, Shenyang 110122, China; Cancer Hospital of China Medical University, Liaoning Cancer Hospital & Institute, Shenyang 110042, China.
Department of Microbiology and Parasitology, China Medical University, Shenyang 110122, China.
Genomics. 2021 Jul;113(4):2253-2263. doi: 10.1016/j.ygeno.2021.05.026. Epub 2021 May 21.
Circular RNAs (circRNAs) are highly stable forms of endogenous non-coding RNA molecules with diverse biological functions. Some of them have been demonstrated to play crucial roles in the initiation or development of cancers through regulation of gene expression. However, the profiles and the roles of circRNAs in tumorigenesis of cervical cancer remain largely unknown. In the current study, we investigated the expression profiles of circRNAs and their potential oncogenic mechanisms in cervical cancer. The expression patterns, obtained using a microarray assay, revealed a total of 192 differentially expressed circRNAs, of which 106 were upregulated and 86 were downregulated, in cervical cancer samples compared with normal cervical samples. The differential expression of circRNAs was validated using quantitative real-time polymerase chain reaction. Two circRNAs (circTPCN and circFAM185A) were confirmed to be significantly upregulated in cervical cancer samples, indicating that they represent potential biomarkers of cervical cancer. The role and the potential molecular mechanism of circTPCN in cervical cancer tumorigenesis were further investigated. Knockdown of circTPCN significantly suppressed proliferation, migration, and invasion and increased apoptosis of cervical cancer cells in vitro. Molecular analysis revealed that circTPCN acted as a sponge of miR-634 to enhance mTOR expression. Thus, the circTPCN/miR-634/mTOR regulatory pathway might be involved in cervical cancer tumorigenesis, and circTPCN is a potential therapeutic target in cervical cancer.
环状RNA(circRNAs)是内源性非编码RNA分子的高度稳定形式,具有多种生物学功能。其中一些已被证明通过调节基因表达在癌症的发生或发展中发挥关键作用。然而,circRNAs在宫颈癌发生中的特征和作用仍 largely unknown。在本研究中,我们调查了circRNAs在宫颈癌中的表达谱及其潜在的致癌机制。使用微阵列分析获得的表达模式显示,与正常宫颈样本相比,宫颈癌样本中共有192种差异表达的circRNAs,其中106种上调,86种下调。circRNAs的差异表达通过定量实时聚合酶链反应进行验证。两种circRNAs(circTPCN和circFAM185A)在宫颈癌样本中被证实显著上调,表明它们代表宫颈癌的潜在生物标志物。进一步研究了circTPCN在宫颈癌发生中的作用和潜在分子机制。在体外,敲低circTPCN显著抑制了宫颈癌细胞的增殖、迁移和侵袭,并增加了其凋亡。分子分析表明,circTPCN作为miR-634的海绵来增强mTOR表达。因此,circTPCN/miR-634/mTOR调节通路可能参与宫颈癌的发生,circTPCN是宫颈癌的潜在治疗靶点。