Reactivation of protective p53 anti-cancer target eIF4A3 debut

Article source: Medical Rubik's Cube Pro

Author: Bai Lu

As we all know, the process of cell growth and division is controlled by genes.

Recently, scientists at the Karolinska Institute in Sweden have locked on one of these proteins, eIF4A3

This study first demonstrated through the analysis of public cancer patient data that the high expression of eIF4A3 in cancer is associated with increased ribosome biogenesis (RiBi) and poor prognosis

The high expression of eIF4A3 in cancer is correlated with elevated RiBi and poor prognosis

Studies have also shown that deletion of eIF4A3 disrupts the process of RiBi, thereby altering the production of proteins in cancer cells

eIF4A3, also known as DDX48, is an ATP-dependent RNA helicase, belonging to the eIF4A family

Ribosomes are important organelles for protein synthesis in cells, and the process of synthesizing new ribosomes is defined as RiBi

Graphical model summary of the role of eIF4A3 in splicing, RiBi and MDM2-p53 control

This shows that blocking eIF4A3 will activate p53

Because about 50% of human cancers retain the wild-type p53 gene, but the tumor suppressor function of these p53 is weakened by signal molecules such as MDM2.

The elF4A3 blocker seems to be able to solve this problem

Further studies have shown that EIF4A3 deletion induces cell cycle arrest through IRBC-mediated p53 induction and reprogramming of cell cycle regulator transcription

The loss of EIF4A3 reduces the survival rate of osteosarcoma U2OS cells in a time-dependent manner

The results of these studies will help select patients most likely to respond to eIF4A3 inhibition

The researchers believe that there may be a synergy between the anti-cancer drugs and eIF4A3 receptor inhibitors already in use.

Note: The original text has been deleted

Reference materials:

1# Stopping cancer cells by blocking a growth-promoting protein and reactivating protective p53 (Source: FIERCE Biotech)

2# Dimitris C.