Comparative Proteomic Analysis of Irradiation-Induced Radioresistant Breast Cancer Cells Using Label-Free Quantitation

Yingxia Ying; Lei Bian; Yiling Meng; Meichao Zhang; Yuan Yao; Fang Bo; Dong Li

doi:10.31083/j.fbl2810244

Comparative Proteomic Analysis of Irradiation-Induced Radioresistant Breast Cancer Cells Using Label-Free Quantitation

Front Biosci (Landmark Ed). 2023 Oct 19;28(10):244. doi: 10.31083/j.fbl2810244.

Authors

Yingxia Ying¹, Lei Bian^{1

2}, Yiling Meng¹, Meichao Zhang¹, Yuan Yao¹, Fang Bo³, Dong Li¹

Affiliations

¹ Department of Radiation Oncology, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 200011 Shanghai, China.
² Department of Breast Oncology, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, 510060 Guangzhou, Guangdong, China.
³ Disinfection Supply Center, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, 200011 Shanghai, China.

PMID: 37919065
DOI: 10.31083/j.fbl2810244

Abstract

Background: Breast cancer poses severe threats to human health as radioresistance becomes increasingly prevalent. The mechanisms of radioresistance are hard to expound completely. This study aims to explore proteomic changes of radioresistance, which will help elucidate the potential mechanisms responsible for breast cancer radioresistance and explore potential therapeutic targets.

Methods: A radioresistant breast cancer cell line was established by repeated irradiation. Liquid Chromatograph Mass Spectrometer (LC-MS) was used to quantify protein expression. Proteomic changes associated with radioresistance were evaluated by proteomic analysis. Further, cell radioresistance and several identified proteins were verified in in vitro experiments.

Results: In the study, more than 3000 proteins were detected, 243 of which were identified as up-regulated proteins and another 633 as down-regulated proteins. Gene Ontology (GO) enrichment analysis indicated that these proteins were mainly expressed in the lysosome and ribosome, associated with coenzyme binding and the structural constituent of the ribosome, involved in mitotic cytokinesis and ribonucleoprotein complex biogenesis. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated that many biological processes were extensively altered, particularly spliceosome and thermogenesis. It is worth noting that the functions and pathways related to ribosomes were significantly enriched, therefore ribosomal proteins (RPL6 and RPS13) were identified through western blot and highly expressed in relatively radiosensitive cells. Additionally, several identified proteins, including S100A4, RanBP9, and ISG15, were also verified to be differentially expressed in different radiosensitive cells.

Conclusions: Our results provide a framework for further studies into the mechanisms of radioresistance and serve as a basis to construct a predictive model of radioresistance in breast cancer. Ribosome may participate in the radioresistance of breast cancer, which provides new insights into the proteomic characteristics of the mechanisms of radioresistance.

Keywords: bioinformatics analysis; breast cancer; proteomic analysis; radioresistance; ribosome.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Breast Neoplasms* / genetics
Breast Neoplasms* / radiotherapy
Cell Line, Tumor
Female
Humans
Proteins
Proteomics
Radiation Tolerance / genetics

Substances

Proteins