Panahi-Moghadam Somayeh, Sadeghizadeh Majid, Farivar Shirin, Vakhshiteh Faezeh
Department of Molecular Genetics, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, 14115154, Iran.
Department of Cell and Molecular Biology, Faculty of Life Sciences and Biotechnology, Shahid Beheshti University, Tehran, 1983963113, Iran.
Sci Rep. 2025 Jul 2;15(1):23155. doi: 10.1038/s41598-025-07237-6.
Cervical cancer (CC) poses a significant global health challenge, necessitating the development of novel therapeutic strategies. The interplay between the p63 isoform (ΔNp63), microRNA-141-3p (miR-141-3p), and Yes-associated protein 1 (YAP1) has emerged as a potential area of interest in cancer progression. This study aimed to investigate the functional relationship between the between the p63 isoform (ΔNp63), miR-141-3p and YAP1 in modulating migration, invasion, and epithelial-mesenchymal transition (EMT) in two CC cell lines, CaSki, and HeLa, which are human cervical squamous cell carcinoma (SCC) and adenocarcinoma (ADC) cells, respectively. The Gene Expression Omnibus (GEO) datasets, were utilized to assess the expression profiles of TP63 and YAP1 in the cervical SCC and ADC samples by using the GEO2R tool. The prediction software (miRDIP, miRmap, and TargetScan), and RT-qPCR were used to determine the relationship between genes. Different assays were performed for proliferative, migratory and invasive abilities of cells. The results were confirmed by western blot analysis. The ΔNp63-miR-141-3p-YAP1 axis exhibited distinct, cell-line-specific functions. In HeLa cells, this axis promoted a prometastatic phenotype by upregulating YAP1, leading to increased proliferation, migration, invasion, and EMT. Conversely, in CaSki cells, the same axis demonstrated an antimetastatic function by downregulating YAP1. YAP1 expression was significantly higher in HeLa cells compared to CaSki cells. In HeLa cells, YAP1 expression appeared to be regulated not solely by the upstream ΔNp63-miR-141-3p axis, suggesting its role as a key oncogene in HeLa cell progression. MiR-141-3p demonstrated context-dependent effects, exhibiting both pro- and anti-metastatic activities depending on the specific cell line. These findings highlight the complex and subtype-specific functions of the ΔNp63-miR-141-3p-YAP1 regulatory network in cervical cancer progression. In summary, our data highlights the different functions of ΔNp63-miR-141-3p-YAP1 axis in regulating proliferation, migration and invasion as well as EMT of different cervical cancer cells.
宫颈癌（CC）是一项重大的全球健康挑战，因此需要开发新的治疗策略。p63亚型（ΔNp63）、微小RNA - 141 - 3p（miR - 141 - 3p）和Yes相关蛋白1（YAP1）之间的相互作用已成为癌症进展中一个潜在的研究热点。本研究旨在探讨p63亚型（ΔNp63）、miR - 141 - 3p和YAP1在调节两种CC细胞系（CaSki和HeLa，分别为人宫颈鳞状细胞癌（SCC）和腺癌（ADC）细胞）的迁移、侵袭和上皮 - 间质转化（EMT）中的功能关系。利用基因表达综合数据库（GEO）数据集，通过GEO2R工具评估宫颈SCC和ADC样本中TP63和YAP1的表达谱。使用预测软件（miRDIP、miRmap和TargetScan）以及逆转录定量聚合酶链反应（RT - qPCR）来确定基因之间的关系。对细胞的增殖、迁移和侵袭能力进行了不同的检测。结果通过蛋白质免疫印迹分析得到证实。ΔNp63 - miR - 141 - 3p - YAP1轴表现出不同的、细胞系特异性的功能。在HeLa细胞中，该轴通过上调YAP1促进促转移表型，导致增殖、迁移、侵袭和EMT增加。相反，在CaSki细胞中，同一轴通过下调YAP1表现出抗转移功能。HeLa细胞中YAP1的表达明显高于CaSki细胞。在HeLa细胞中，YAP1的表达似乎不仅受上游ΔNp63 - miR - 141 - 3p轴的调节，这表明它在HeLa细胞进展中作为关键癌基因的作用。miR - 141 - 3p表现出背景依赖性效应，根据特定细胞系表现出促转移和抗转移活性。这些发现突出了ΔNp63 - miR - 141 - 3p - YAP1调控网络在宫颈癌进展中的复杂和亚型特异性功能。总之，我们的数据突出了ΔNp63 - miR - 141 - 3p - YAP1轴在调节不同宫颈癌细胞的增殖、迁移、侵袭以及EMT方面的不同功能。
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