# TIMAP downregulation in Burkitt’s lymphoma reveals key molecules and signaling pathways in B-cell lymphomagenesis

## TL;DR

This study shows that reducing TIMAP in Burkitt’s lymphoma cells changes gene activity and affects cancer-related pathways, suggesting TIMAP is important in B-cell lymphoma development.

## Contribution

The study identifies TIMAP as a key regulator of gene expression and signaling pathways in B-cell lymphomagenesis through transcriptomic analysis.

## Key findings

- TIMAP downregulation significantly altered 2,368 genes, with key roles in DNA replication and apoptosis.
- TIMAP affects pathways like B-cell receptor signaling, p53, and mTOR, which are linked to lymphoma progression.
- Genes such as PAK3, LINC00487, AID, PURPL, and BCL2 were notably dysregulated, indicating TIMAP’s role in oncogenesis.

## Abstract

Burkitt’s lymphoma (BL) is an aggressive subtype of B-cell non-Hodgkin’s lymphoma, known for its rapid tumor growth and poor prognosis. Transforming growth factor beta-inhibited membrane-associated protein (TIMAP) is a regulatory subunit of protein phosphatase 1 catalytic subunit, enriched in lymphoid tissues, and upregulated in various cancers. Despite suggestions that TIMAP promotes lymphomagenesis in a c-myc-driven model, its precise role remains unclear. This study aimed to investigate the contribution of TIMAP to B-cell lymphomagenesis by examining transcriptomic changes upon TIMAP downregulation in BL cells. Raji BL cells were transfected with 2′Fluoro Arabinonucleic acid (FANA)-antisense oligonucleotides (ASO) targeting TIMAP (FANA-ASO-TIMAP) or a scramble control (FANA-ASO-Scramble). TIMAP expression was significantly reduced at the mRNA (0.70 ± 0.04, p = 0.001) and protein levels (median = 0.73, IQR = 0.13, p = 0.002). RNA sequencing identified 2,368 differentially expressed genes (DEGs), of which 1,326 were upregulated, and 1,042 were downregulated. Gene Ontology analysis revealed that the DEGs were primarily involved in cellular processes, DNA replication, intracellular signal transduction, and apoptosis. Pathways related to lymphoma progression, such as B-cell receptor signaling, p53 signaling, and mTOR signaling, were notably affected. Key genes such as PAK3, LINC00487, AID, PURPL, and BCL2 were among the most dysregulated, highlighting TIMAP’s role in critical oncogenic pathways in B-cell Lymphoma. These findings suggest that TIMAP is a key regulator of gene expression and signaling pathways in B-cell lymphomagenesis and could serve as a potential therapeutic target for novel treatments.