Cancer Biomark. 2020;28(3):381-390. doi: 10.3233/CBM-191064.
MicroRNAs (MiRNAs) have been clarified as crucial regulators of the pathological processes in various carcinomas in the past years. Interestingly, existing evidence has manifested that microRNA-204-5p (miR-204-5p) is engaged in the initiation and progression of multiple carcinomas. However, the potential of miR-204-5p in cervical cancer remains to be disentombed. This study focused on unraveling the detailed role of miR-204-5p in cervical cancer. MiR-204-5p exhibited a low level in cervical cancer cells. The functional assays demonstrated that miR-204-5p upregulation exerted suppressive impact on the functions of cervical cancer cells, including proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) process. Moreover, transcription factor AP-2 alpha (TFAP2A) was screened to be the most affected target gene by miR-204-5p, and TFAP2A was discovered to transcriptionally repress miR-204-5p in cervical cancer. The mutual regulation between TFAP2A and miR-204-5p was testified through molecular mechanism assays. Final rescued-function assays demonstrated that overexpression of TFAP2A could recover the suppressed cellular process caused by miR-204-5p upregulation. In conclusion, miR-204-5p/TFAP2A feedback loop promoted the proliferative and motorial capacities of cervical cancer cells. This finding suggested a novel modulatory loop of miR-204-5p/TFAP2A in cervical cancer, offering promising biomarkers for cervical cancer therapy.
近年来,microRNAs(miRNAs)已被阐明为多种癌中病理过程的关键调节因子。有趣的是,现有证据表明 microRNA-204-5p(miR-204-5p)参与了多种癌的发生和发展。然而,miR-204-5p 在宫颈癌中的潜在作用仍有待揭示。本研究旨在阐明 miR-204-5p 在宫颈癌中的详细作用。miR-204-5p 在宫颈癌细胞中呈现低水平。功能分析表明,miR-204-5p 的上调对宫颈癌细胞的功能,包括增殖、侵袭、迁移和上皮-间充质转化(EMT)过程,具有抑制作用。此外,筛选出转录因子 AP-2 alpha(TFAP2A)是受 miR-204-5p 影响最大的靶基因,并且发现 TFAP2A 在宫颈癌中转录抑制 miR-204-5p。通过分子机制分析验证了 TFAP2A 和 miR-204-5p 之间的相互调节。最终的恢复功能分析表明,TFAP2A 的过表达可以恢复 miR-204-5p 上调引起的细胞过程抑制。总之,miR-204-5p/TFAP2A 反馈环促进了宫颈癌细胞的增殖和运动能力。这一发现提示了 miR-204-5p/TFAP2A 在宫颈癌中的新型调节环,为宫颈癌治疗提供了有前景的生物标志物。