Related Experiment Video
Updated: Aug 15, 2025

Identification of Transcription Factor Regulators using Medium-Throughput Screening of Arrayed Libraries and a Dual-Luciferase-Based Reporter
Published on: March 27, 2020
RNF31 represses cell progression and immune evasion via YAP/PD-L1 suppression in triple negative breast Cancer
Huijie Yang1, Min Xue2, Peng Su3
1Xinxiang Key Laboratory of Tumor Migration and Invasion Precision Medicine, School of Laboratory Medicine, Xinxiang Medical University, Xinxiang, 453003, Henan Province, People's Republic of China.
Background:
Recently genome-based studies revealed that the abnormality of Hippo signaling is pervasive in TNBC and played important role in cancer progression. RING finger protein 31 (RNF31) comes to RING family E3 ubiquitin ligase. Our previously published studies have revealed RNF31 is elevated in ER positive breast cancer via activating estrogen signaling and suppressing P53 pathway.
Methods:
We used several TNBC cell lines and xenograft models and performed immuno-blots, QPCR, in vivo studies to investigate the function of RNF31 in TNBC progression.
Result:
Here, we demonstrate that RNF31 plays tumor suppressive function in triple negative breast cancer (TNBC). RNF31 depletion increased TNBC cell proliferation and migration in vitro and in vitro. RNF31 depletion in TNBC coupled with global genomic expression profiling indicated Hippo signaling could be the potential target for RNF31 to exert its function. Further data showed that RNF31 depletion could increase the level of YAP protein, and Hippo signaling target genes expression in several TNBC cell lines, while clinical data illustrated that RNF31 expression correlated with longer relapse-free survival in TNBC patients and reversely correlated with YAP protein level. The molecular biology assays implicated that RNF31 could associate with YAP protein, facilitate YAP poly-ubiquitination and degradation at YAP K76 sites. Interestingly, RNF31 could also repress PDL1 expression and sensitive TNBC immunotherapy via inhibiting Hippo/YAP/PDL1 axis.
Conclusions:
Our study revealed the multi-faced function of RNF31 in different subtypes of breast malignancies, while activation RNF31 could be a plausible strategy for TNBC therapeutics.
Insights
RING finger protein 31 (RNF31) suppresses tumors in triple-negative breast cancer (TNBC) by inhibiting the Hippo/YAP pathway. Activating RNF31 may offer a new therapeutic strategy for TNBC, potentially improving immunotherapy response.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Signaling Pathways
Background:
- Hippo signaling pathway abnormalities are common in triple-negative breast cancer (TNBC) and drive cancer progression.
- RING finger protein 31 (RNF31), an E3 ubiquitin ligase, is known to be elevated in ER-positive breast cancer.
- Previous research indicated RNF31's role in activating estrogen signaling and suppressing the P53 pathway in ER-positive breast cancer.
Purpose of the Study:
- To investigate the function of RNF31 in the progression of triple-negative breast cancer (TNBC).
- To explore the potential of RNF31 as a therapeutic target for TNBC.
Main Methods:
- Utilized TNBC cell lines and xenograft models for in vitro and in vivo studies.
- Performed immuno-blots, QPCR, and global genomic expression profiling.
- Conducted molecular biology assays to examine protein interactions and ubiquitination.
Main Results:
- RNF31 exhibits a tumor-suppressive function in TNBC, with RNF31 depletion increasing cell proliferation and migration.
- RNF31 depletion upregulates YAP protein and Hippo signaling target genes, indicating Hippo signaling as a target.
- RNF31 expression correlates with longer relapse-free survival in TNBC patients and represses PDL1 expression, sensitizing TNBC to immunotherapy via the Hippo/YAP/PDL1 axis.
Conclusions:
- RNF31 plays a multifaceted role in different breast cancer subtypes.
- Activation of RNF31 presents a potential therapeutic strategy for TNBC.
- Targeting the Hippo/YAP/PDL1 axis through RNF31 modulation could enhance TNBC immunotherapy outcomes.
More Related Videos
10:32Combined Use of Tail Vein Metastasis Assays and Real-Time In Vivo Imaging to Quantify Breast Cancer Metastatic Colonization and Burden in the Lungs
Published on: December 19, 2019
13:38Synthesis and Characterization of an Aspirin-fumarate Prodrug that Inhibits NFκB Activity and Breast Cancer Stem Cells
Published on: January 18, 2017
Related Concept Videos
Negative Regulator Molecules
Abnormal Proliferation
The Retinoblastoma Gene
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
The Intrinsic Apoptotic Pathway
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...