Identification of the potential roles of ring finger protein 8 in TP53-mutant breast cancer.

ABSTRACT: 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.

SUBMITTER: Zhao F 

PROVIDER: S-EPMC7693390 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature