Identification and Multi-omic Analysis of Essential Coding and Long Non-conding Genes in Colorectal Cancer
Abstract Essential genes are indispensable for the survival of cancer cell. CRISPR/Cas9-based pooled genetic screens have distinguished the pan-cancer 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) via cell-to-cell communication network (CCN) 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 a full-length single cells transcriptome 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 single cell transcriptome data. CRISPR/Cas9 knockout experiment verified the effect of several ESPs and ESLs on the survival of CRC cell line. Furthermore, multiple 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 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..
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Preprint| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
ResearchSquare.com - (2024) vom: 13. März Zur Gesamtaufnahme - year:2024 |
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| Sprache: |
Englisch |
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| Beteiligte Personen: |
Li, Yanguo [VerfasserIn] |
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| Links: |
Volltext [kostenfrei] |
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| doi: |
10.21203/rs.3.rs-4034323/v1 |
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| 520 | |a Abstract Essential genes are indispensable for the survival of cancer cell. CRISPR/Cas9-based pooled genetic screens have distinguished the pan-cancer 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) via cell-to-cell communication network (CCN) 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 a full-length single cells transcriptome 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 single cell transcriptome data. CRISPR/Cas9 knockout experiment verified the effect of several ESPs and ESLs on the survival of CRC cell line. Furthermore, multiple 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 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. | ||
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| 700 | 1 | |a Wang, Huifang |4 aut | |
| 700 | 1 | |a Yu, Chen |4 aut | |
| 700 | 1 | |a Xi, Yang |4 aut | |
| 700 | 1 | |a Liao, Qi |4 aut | |
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