RING finger protein 180 (RNF180), an E3 ubiquitin ligase, is thought to be a tumor suppressor gene. However, the detailed mechanism of its effect on ovarian cancer (OV) has not been elucidated. Importin 4 (IPO4) which belongs to transport protein is reported to have cancer-promoting effects on OV. Here, we explored the potential signaling pathways related to RNF180 and IPO4. It was first verified that RNF180 is downregulated and IPO4 is upregulated in OV. By overexpressing or knocking down RNF180 in OV cells, we confirmed that RNF180 inhibited the malignant behaviors of OV cells both in vitro and in vivo. Bioinformatics analysis and proteomics experiments found that RNF180 could interact with IPO4 and promote the degradation of IPO4 through ubiquitination. In addition, overexpression of IPO4 removed the inhibitory effect of RNF180 on OV. We subsequently found that IPO4 could bind to the oncogene Sex determining Region Y-box 2 (SOX2). Knockdown of IPO4 in OV cells decreased SOX2 protein level in nucleus and promoted cyclin-dependent kinase inhibitory protein-1 (p21) expression. Overexpression of RNF180 also inhibited the expression of SOX2 in nucleus. All these results indicated that RNF180 inhibited the nuclear translocation of SOX2 by promoting ubiquitination of IPO4, which ultimately promoted the expression of p21 and then suppressed the progression of OV. This study verified the tumor suppressor effect of RNF180 on OV, elucidated the mechanism of the molecule network related to RNF180 and IPO4 in OV and identified for OV.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.cellsig.2023.110961 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Plasma DNA methylation detection for early screening, diagnosis, and monitoring of esophageal adenocarcinoma and squamous cell carcinoma.
World J Gastroenterol
November 2024
Department of Radiotherapy and Oncology, Wuhan Sixth Hospital and Affiliated Hospital of Jianghan University, Wuhan 430015, Hubei Province, China.
Article Synopsis
- Esophageal cancer (EC) diagnosis is challenging due to low early detection rates, prompting this study to explore the role of plasma methylation markers in diagnosing and monitoring the disease.
- The research involved analyzing plasma samples from 210 patients using TaqMan polymerase chain reaction to measure methylation, with results showing promising sensitivity and specificity for differentiating various types of esophageal cancer.
- The findings suggest that plasma methylation markers could significantly enhance the accuracy of EC diagnosis and improve treatment monitoring.
Combining methylated RNF180 and SFRP2 plasma biomarkers for noninvasive diagnosis of gastric cancer.
Transl Oncol
January 2025
School of Public Health, Nanjing Medical University, Nanjing, 211166, China; Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, 310000, Zhejiang, China; Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310000, China. Electronic address:
Introduction: Gastric cancer (GC) is a common malignant tumor, and early diagnosis significantly improves patient survival rates. This study aimed to investigate the diagnostic value of ring finger protein 180 (RNF180) and secreted frizzled protein 2 (SFRP2) in GC.
Materials & Methods: A total of 165 healthy individuals, 34 patients with precancerous gastric lesions, and 104 patients with confirmed GC were divided into training and validation sets; methylated RNF180 and SFRP2 were detected in circulating DNA from blood samples.
Diagnostic efficacy of SEPT9 and PAX5 gene methylation in gastrointestinal cancer and precancerous lesions.
Cell Mol Biol (Noisy-le-grand)
July 2024
Department of Gastroenterology, Huai'an Huai'an Hospital, Huai'an, Jiangsu 223200, China.
To assess the diagnostic efficacy of SEPT9 along with PAX5 gene methylation detection in gastrointestinal cancer and precancerous lesions, the peripheral blood of 62 patients with gastric cancer (GC) and 60 patients with no evidence of disease (as the control group) were retrospectively collected. The methylation rates of PAX5 and SEPT9 gene promoters in blood samples of GC group were detected by PCR. At the same time, the differences in methylation rates of genes in the two groups were compared, and the predictive value of plasma methylation PAX5 and SEPT9 in GC was evaluated by receiver operating characteristic (ROC) curve.
View Article and Find Full Text PDFE3 ubiquitin ligase RNF180 mediates the ALKBH5/SMARCA5 axis to promote colon inflammation and Th17/Treg imbalance in ulcerative colitis mice.
Arch Pharm Res
July 2024
Department of Gastroenterology, Xiangya Hospital, Central South University, Changsha, 410008, Hunan, People's Republic of China.
SMARCA5, a protein in the SWI/SNF family, has been previously implicated in the development of ulcerative colitis (UC) through methylation. However, the specific molecular mechanisms by which SMARCA5 contributes to colonic inflammation and the imbalance between Th17 and Treg cells remain unclear. This study was designed to explore these molecular mechanisms.
View Article and Find Full Text PDFE3 ubiquitin ligase RNF180 impairs IPO4/SOX2 complex stability and inhibits SOX2-mediated malignancy in ovarian cancer.
Cell Signal
January 2024
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China. Electronic address:
RING finger protein 180 (RNF180), an E3 ubiquitin ligase, is thought to be a tumor suppressor gene. However, the detailed mechanism of its effect on ovarian cancer (OV) has not been elucidated. Importin 4 (IPO4) which belongs to transport protein is reported to have cancer-promoting effects on OV.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!