Zhao Feng, Wang Peibin, Guo Yan, Lu Qi, Kong Xu, Su Dongwei, Li Hengyu, Liu Guoping, Liu Chaoqian
Anhui Province Engineering Laboratory of Occupational Health and Safety, Anhui University of Science and Technology, Huainan, Anhui 232000, P.R. China.
Department of General Surgery, Huainan First People's Hospital Affiliated to Bengbu Medical College, Huainan, Anhui 232000, P.R. China.
Oncol Lett. 2021 Jan;21(1):42. doi: 10.3892/ol.2020.12303. Epub 2020 Nov 17.
Breast cancer is one of the malignant tumors with the highest mortality rate. With the development of precise treatment technology for cancer, numerous molecular targets have been identified and applied in the treatment of diseases. The present study investigated the potential role of ring finger protein 8 (RNF8) in TP53-mutant breast cancer and explored its possible mechanisms of action through a combination of bioinformatics techniques and cell biology. The results revealed that significantly different genes were expressed in RNF8-knockout mice sequencing data compared with in the control group in the presence of TP53 mutations. Downregulated genes were significantly enriched in several pathways of cell proliferation and apoptosis regulation, development and transcription regulation, while upregulated genes were mainly enriched in immune response-associated signaling pathways. Therefore, the consensus genes of the major signaling pathways were further analyzed, revealing that among patients with TP53 wild-type breast cancer, the prognosis of patients with low expression levels of fibroblast growth factor receptor 1, LIM homeobox 2 and EPH receptor B2 was improved compared with that of patients with high expression levels, while among patients with TP53-mutant breast cancer, there was no significant difference in survival status. In addition, among patients with TP53-mutant breast cancer, the prognosis of patients with high BR serine/threonine kinase 1 expression was significantly improved compared with that in patients with low expression. Finally, cell biology experiments demonstrated that in TP53-mutant breast cancer cells (HCC1937), inhibition of RNF8 significantly inhibited the proliferation of TP53-mutant HCC1937 cells and promoted their apoptosis. The present findings may enrich the understanding of the role of RNF8 and indicated that RNF8 may be used as a potential molecular target in TP53-mutant breast cancer, which may lead to the development of clinical treatment strategies.
乳腺癌是死亡率最高的恶性肿瘤之一。随着癌症精准治疗技术的发展,众多分子靶点已被识别并应用于疾病治疗。本研究通过生物信息学技术与细胞生物学相结合的方法,探究了环指蛋白8(RNF8)在TP53突变型乳腺癌中的潜在作用,并探讨了其可能的作用机制。结果显示,在存在TP53突变的情况下,与对照组相比,RNF8基因敲除小鼠测序数据中表达有显著差异的基因。下调基因在细胞增殖和凋亡调控、发育及转录调控的多个途径中显著富集,而上调基因主要富集在免疫反应相关信号通路中。因此,对主要信号通路的共有基因进行了进一步分析,结果表明,在TP53野生型乳腺癌患者中,成纤维细胞生长因子受体1、LIM同源盒2和EPH受体B2低表达患者的预后较其高表达患者有所改善,而在TP53突变型乳腺癌患者中,生存状况无显著差异。此外,在TP53突变型乳腺癌患者中,BR丝氨酸/苏氨酸激酶1高表达患者的预后较其低表达患者有显著改善。最后,细胞生物学实验表明,在TP53突变型乳腺癌细胞(HCC1937)中,抑制RNF8可显著抑制TP53突变型HCC1937细胞的增殖并促进其凋亡。本研究结果可能会丰富对RNF8作用的认识,并表明RNF8可能作为TP53突变型乳腺癌的潜在分子靶点,这可能会推动临床治疗策略的发展。