Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to Metastatic Triple-Negative Breast Cancer

Yining Liu; Min Zhao

doi:10.3390/ph14090918

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Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to Metastatic Triple-Negative Breast Cancer

Journal article

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Peer reviewed

Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to Metastatic Triple-Negative Breast Cancer

Yining Liu and Min Zhao

Pharmaceuticals, Vol.14(9), pp.1-14

2021

DOI: https://doi.org/10.3390/ph14090918

Appears in Cancer Research Cluster Research Collection

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Abstract

copy number variation

dosage effect

metastatic triple-negative breast cancer

signal recognition particle

single-cell RNA sequencing

Many recent efforts have been put into the association between expression heterogeneity and different cell types and states using single-cell RNA transcriptome analysis. There is only limited understanding of gene dosage effects for the genetic heterogeneity at the single-cell level. By focusing on concordant copy number variation (CNV) and expression, we presented a computational framework to explore dosage effect for aggressive metastatic triple-negative breast cancer (TNBC) at the single-cell level. In practice, we collected CNV and single-cell expression data from the same patients with independent technologies. By focusing on 47,198 consistent copy number gains (CNG) and gene up-regulation from 1145 single cells, ribosome proteins with important roles in protein targeting were enriched. Independent validation in another metastatic TNBC dataset further prioritized signal recognition particle-dependent protein targeting as the top functional module. More interesting, the increased ribosome gene copies in TNBC may associate with their enhanced stemness and metastatic potential. Indeed, the prioritization of a well-upregulated functional module confirmed by high copy numbers at the single-cell level and contributing to patient survival may indicate the possibility of targeted therapy based on ribosome proteins for TNBC.

Details

Title: Gene Dosage Analysis on the Single-Cell Transcriptomes Linking Cotranslational Protein Targeting to Metastatic Triple-Negative Breast Cancer
Authors: Yining Liu (Author) - Guangzhou Medical University
Min Zhao (Author) - University of the Sunshine Coast, Queensland
Publication details: Pharmaceuticals, Vol.14(9), pp.1-14
Publisher: MDPI AG
Date published: 2021
DOI: 10.3390/ph14090918
ISSN: 1424-8247
Copyright note: Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Organisation Unit: University of the Sunshine Coast, Queensland; GeneCology Research Centre - Legacy; Cancer Research Cluster; School of Science, Technology and Engineering; Centre for Bioinnovation
Language: English
Record Identifier: 99573508602621
Output Type: Journal article

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Collaboration types: Domestic collaboration; International collaboration
Web Of Science research areas: Chemistry, Medicinal; Pharmacology & Pharmacy

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