Properties and gene expression profiling of acquired radioresistance in mouse breast cancer cells

Feng Qin; Qiang Fan; Peter K N Yu; Waleed Abdelbagi Almahi; Peizhong Kong; Miaomiao Yang; Wei Cao; Lili Nie; Guodong Chen; Wei Han

doi:10.21037/atm-20-4667

Properties and gene expression profiling of acquired radioresistance in mouse breast cancer cells

Ann Transl Med. 2021 Apr;9(8):628. doi: 10.21037/atm-20-4667.

Authors

Feng Qin^{1

2

3

4}, Qiang Fan^{1

2}, Peter K N Yu^{5

6}, Waleed Abdelbagi Almahi^{1

2}, Peizhong Kong^{1

2}, Miaomiao Yang^{1

2

7}, Wei Cao^{1

2}, Lili Nie^{1

3}, Guodong Chen^{1

3}, Wei Han^{1

3

8}

Affiliations

¹ Anhui Province Key Laboratory of Medical Physics and Technology/Institute of Health and Medical Technology, Hefei Institutes of Physical Sciences, Chinese Academy of Sciences, Hefei, China.
² Scinece Island Branch, Graduate School of USTC, Hefei, China.
³ Hefei Cancer Hospital, Chinese Academy of Sciences, Hefei, China.
⁴ Institute of Sericultural, Anhui Academy of Agricultural Sciences, Hefei, China.
⁵ Department of Physics, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong, China.
⁶ State Key Laboratory in Marine Pollution, City University of Hong Kong, Tat Chee Avenue, Kowloon Tong, Hong Kong, China.
⁷ Clinical Pathology Center, The Fourth Affiliated Hospital of Anhui Medical University, Hefei, China.
⁸ Collaborative Innovation Center of Radiation Medicine of Jiangsu Higher Education Institutions and School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou, China.

Abstract

Background: Acquired radioresistant cells exhibit many characteristic changes which may influence cancer progression and further treatment options. The purpose of this study is to investigate the changes of radioresistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells on both phenotypic and molecular levels.

Methods: We established an acquired radioresistant cell line from its parental NF639 cell line (HER2-positive) by fractionated radiation and assessed changes in cellular morphology, proliferation, migration, anti-apoptosis activity, basal reactive oxygen species (ROS) level and energy metabolism. RNA-sequencing (RNA-seq) was also used to reveal the potential regulating genes and molecular mechanisms associated with the acquired changed phenotypes. Real-time PCR was used to validate the results of RNA-seq.

Results: The NF639R cells exhibited increased radioresistance and enhanced activity of proliferation, migration and anti-apoptosis, but decreased basal ROS. Two main energy metabolism pathways, mitochondrial respiration and glycolytic, were also upregulated. Furthermore, 490 differentially expressed genes were identified by RNA-seq. Enrichment analysis based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes showed many differently expressed genes were significantly enriched in cell morphology, proliferation, migration, anti-apoptosis, antioxidation, tumor stem cells and energy metabolism and the signaling cascades such as the transforming growth factor-β, Wnt, Hedgehog, vascular endothelial growth factor, retinoic acid-inducible gene I (RIG-I)-like receptor, Toll-like receptor and nucleotide oligomerization domain (NOD)-like receptor were significantly altered in NF639R cells.

Conclusions: In clinical radiotherapy, repeat radiotherapy for short-term recurrence of breast cancer may result in enhanced radioresistance and promote malignant progression. Our research provided hints to understand the tumor resistance to radiotherapy de novo and recurrence with a worse prognosis following radiotherapy.

Keywords: Breast cancer; acquired radioresistance; energy metabolism; gene expression profiling.