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Integrating Multi-Omics Mendelian Randomization and Functional Validation to Identify Novel Apoptosis Regulators in
Bin Zhu1, Suli Wang1, Wenli Zhao1
1Department of Hematology, The Sixth People's Hospital Affiliated to Shanghai Jiaotong University South Branch, Shanghai Fengxian District Central Hospital, Shanghai, China.
Technology in Cancer Research & Treatment
|July 23, 2026
Summary
This study identifies IER3IP1 as a novel oncogene in follicular lymphoma (FL), promoting cancer growth and resistance to Rituximab therapy. Targeting IER3IP1 may restore apoptosis and improve treatment outcomes for FL patients.
Area of Science:
- Oncology
- Genetics
- Molecular Biology
Background:
- Dysregulation of apoptosis is a key feature of follicular lymphoma (FL).
- The genetic drivers influencing apoptosis in FL are not fully understood.
- Identifying these drivers is crucial for developing targeted therapies.
Purpose of the Study:
- To identify and functionally validate apoptosis-related genes causally linked to FL.
- To investigate the role of identified genes in FL pathogenesis and treatment response.
- To explore potential therapeutic targets for follicular lymphoma.
Main Methods:
- Multi-omics Mendelian randomization (MR) study integrating FL GWAS with mQTL, eQTL, and pQTL data.
- Summary data-based MR (SMR) and colocalization analyses for candidate gene identification.
- Validation in external transcriptomic cohorts, FL patient tissues (RT-qPCR), and in vitro functional assays.
Main Results:
- MR analysis identified IER3IP1, PRKCZ, and CD40 as potentially causal genes in FL.
- IER3IP1 mRNA levels were elevated in FL tissues and it functions as an oncogene promoting FL cell proliferation and migration.
- IER3IP1 depletion enhanced FL cell sensitivity to Rituximab by upregulating CD20 via the XBP1/FOXO1 axis.
Conclusions:
- IER3IP1 is a novel causal oncogene in follicular lymphoma pathogenesis.
- The IER3IP1-mediated XBP1/FOXO1/CD20 axis contributes to targeted therapy resistance.
- IER3IP1 represents a promising therapeutic target to enhance Rituximab efficacy in FL.
