[ExI] Reprogramming cancer cells

[Stuart LaForge]

These researchers at the bioengineering departments at the Korea 
Advanced Institute of Science and Technology used computational biology 
techniques to develop a Boolean model of gene regulatory networks in 
cells they call BENEIN. They then used it on human large intestinal 
single-cell transcriptome data to identify three genes MYB, HDAC2, and 
FOXA2 as "master regulatory genes" for differentiation into normal 
intestinal cells. Then they claim that they took three different colon 
cancer cell lines and by knocking down, i.e. shutting off those three 
genes, made the cancer cells back phenotypically normal large intestine 
cells.

https://onlinelibrary.wiley.com/doi/10.1002/advs.202402132

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Control of Cellular Differentiation Trajectories for Cancer Reversion
Jeong-Ryeol Gong, Chun-Kyung Lee, Hoon-Min Kim, Juhee Kim, Jaeog Jeon, 
Sunmin Park,and Kwang-Hyun Cho*

Abstract:
Cellular differentiation is controlled by intricate layers of gene 
regulation, involving the modulation of gene expression by various 
transcriptional regulators. Due to the complexity of gene regulation, 
identifying master regulators across the differentiation trajectory has 
been a longstanding challenge. To tackle this problem, a computational 
framework, single-cell Boolean network inference and control (BENEIN), 
is presented. Applying BENEIN to human large intestinal single-cell 
transcriptome data, MYB,HDAC2, and FOXA2 are identified as the master 
regulators whose inhibition induces enterocyte differentiation. It is 
found that simultaneous knockdown of these master regulators can revert 
colorectal cancer cells into normal-like enterocytes by synergistically 
inducing differentiation and suppressing malignancy, which is validated 
by in vitro and in vivo experiments.

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Note that that they use "in vivo" in a biochemical sense which means 
inside a living cell and not medical "in vivo" which means inside an 
intact organism like a mouse or human.

Stuart LaForge