A Systems Biology Approach to Identifying a Master Regulator That Can Transform the Fast Growing Cellular State to a Slowly Growing One in Early Colorectal Cancer Development Model

Abstract

Colorectal cancer (CRC) has been most extensively studied for characterizing genetic mutations along its development. However, we still have a poor understanding of CRC initiation due to limited measures of its observation and analysis. If we can unveil CRC initiation events, we might identify novel prognostic markers and therapeutic targets for early cancer detection and prevention. To tackle this problem, we establish the early CRC development model and perform transcriptome analysis of its single cell RNA-sequencing data. Interestingly, we find two subtypes, fast growing vs. slowly growing populations of distinct growth rate and gene signatures, and identify CCDC85B as a master regulator that can transform the cellular state of fast growing subtype cells into that of slowly growing subtype cells. We further validate this by in vitro experiments and suggest CCDC85B as a novel potential therapeutic target that may prevent malignant CRC development by suppressing stemness and uncontrolled cell proliferation.