The effect of aberrant expression and genetic polymorphisms of Rad21 on cervical cancer biology

• Published in: Cancer medicine (Malden, MA) Vol. 7; no. 7; pp. 3393 - 3405
• Main Authors: Xia, Li, Wang, Minjie, Li, Hongying, Tang, Xiangjing, Chen, Fei, Cui, Jinquan
• Format: Journal Article
• Language: English
• Published: United States John Wiley & Sons, Inc 01.07.2018; John Wiley and Sons Inc; Wiley
• Subjects: Cancer Biology; Cell cycle; Cell migration; Cell proliferation; Cervical cancer; cervical carcinoma; Cervix; Chromatids; Haplotypes; Human papillomavirus; Mitosis; Original Research; p53 Protein; Rad21; Ribonucleic acid; RNA; single‐nucleotide polymorphism; Sister chromatids; The Cancer Genome Atlas; Tumor suppressor genes; XPO1; XPO1; single-nucleotide polymorphism; Rad21; cervical carcinoma; The Cancer Genome Atlas
• ISSN: 2045-7634; 2045-7634
• DOI: 10.1002/cam4.1592

The therapeutic challenge of advanced, recurrent, and refractory cervical cancer (CC) needs to develop new molecularly targeted drugs. Rad21 is an important regulatory gene that maintains the correct dissociation of sister chromatids during cell mitosis. The aim of this study was to investigate the effect of Rad21 on CC. Rad21 expression in CC and cervical intraepithelial neoplasia III was significantly increased. Women with the rs2289937 C genotype (CC+CT) of rs4570 and rs4579555 genotypes and haplotype 1 (TTTCAGGCGC) were significantly associated with CC risk, while women with low frequencies of haplotype 6 (TTTTAGGCGC) also increased the risk of CC.Rad21‐specific shRNA decreased cancerous cell proliferation, migration, and invasion and increased the proportion of cells in G2/M phase as well as sensitivity to radiation. The Rad21 influenced the expression of XPO1, CyclinB1, CDK1, P21, P27, and P53 through up‐and downregulating the Rad21 expression. The TCGA database of CC also showed that Rad21 expression was associated with poor disease survival and XPO1 expression. Moreover, the KEGG pathway indicated that Rad21 is broadly involved in the cell cycle and RNA transportation via XPO1. This suggests that Rad21 involves the development of cervical cancer possibly by participating in the regulation of cell cycle and the nuclear output of the tumor suppressor gene via XPO1. Rad21 is an important regulatory gene that maintains the correct dissociation of sister chromatids during cell mitosis. Rad21 was found to be associated with the development and prognosis of malignant tumors. Our findings provide important insights into the functions of Rad21 as a potential therapeutic or prognostic target in cervical cancer.