Identification and multi-omics analysis of essential coding and long non-coding genes in colorectal cancer
Year: 2025
Type: article
Abstract: Essential genes are indispensable for the survival of cancer cell. CRISPR/Cas9-based pooled genetic screens have distinguished the essential genes and their functions in distinct cellular processes. Nevertheless, the landscape of essential genes at the single cell levels and the effect on the tumor microenvironment (TME) remains limited. Here, we identified 396 essential protein-coding genes (ESPs) by integration of 8 genome-wide CRISPR loss-of-function screen datasets of colorectal cancer (CRC) cell lines and single-cell RNA sequencing (scRNA-seq) data of CRC tissues. Then, 29 essential long non-coding genes (ESLs) were predicted using Hypergeometric Test (HT) and Personalized PageRank (PPR) algorithms based on ESPs and co-expressed network constructed from scRNA-seq. CRISPR/Cas9 knockout experiment verified the effect of several ESPs and ESLs on the survival of CRC cell line. Furthermore, multi-omics features of ESPs and ESLs were illustrated by examining their expression patterns and transcription factor (TF) regulatory network at the single cell level, as well as DNA mutation and DNA methylation events at bulk level. Finally, through integrating multiple intracellular regulatory networks with cell-cell communication network (CCN), we elucidated that CD47 and MIF are regulated by multiple CRC essential genes, and the anti-cancer drugs sunitinib can interfere the expression of them potentially. Our findings provide a comprehensive asset of CRC ESPs and ESLs, sheding light on the mining of potential therapy targets for CRC. • Identification of 396 essential protein-coding genes in colorectal cancer. • Prediction of 29 essential long non-coding genes utilizing computational methods and scRNA-seq data. • Illustrating the multiple omics features of essential protein-coding and long non-coding genes. • Predicting anti-cancer drugs targeting cell communication and intracellular regulatory networks.
Authors: Yanguo Li, Zixing Meng, Chengjiang Fan, Hao Rong, Yang Xi, Qi Liao
Institution: Ningbo University
Language: English
Subfield: Cancer Research
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,700
OpenAlex ID: W4407479228