ZGRF1 Is Associated with Poor Prognosis in Triple-Negative Breast Cancer and Promotes Cancer Stemness Based on Bioinformatics

Weiyu Ge; Mengyi Jiang; Fengchun Zhang; Yue Ma; Hongxia Wang; Yingchun Xu

doi:10.2147/OTT.S234250

ZGRF1 Is Associated with Poor Prognosis in Triple-Negative Breast Cancer and Promotes Cancer Stemness Based on Bioinformatics

Onco Targets Ther. 2020 Apr 3:13:2843-2854. doi: 10.2147/OTT.S234250. eCollection 2020.

Authors

Weiyu Ge^#¹, Mengyi Jiang^#², Fengchun Zhang^#³, Yue Ma⁴, Hongxia Wang¹, Yingchun Xu^{1

4}

Affiliations

¹ Department of Oncology, Shanghai General Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200080, People's Republic of China.
² Department of Oncology, Shanghai General Hospital, Nanjing Medical University, Nanjing 211166, People's Republic of China.
³ Department of Oncology, Suzhou Kowloon Hospital, Shanghai Jiaotong University School of Medicine, Suzhou 215000, People's Republic of China.
⁴ Department of Oncology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200127, People's Republic of China.

^# Contributed equally.

Abstract

Background: Recently, long non-coding RNAs (lncRNAs) are important populations of non-coding RNAs with defined key roles in normal breast development as well as breast tumorigenesis. Triple-negative breast cancer (TNBC) is a particular breast cancer subtype with poor prognosis because of highly invasive and no specific drug treatment yet. Breast cancer stems cells (BCSCs) cause a high risk of invasion, metastasis and drug resistance for breast cancer patients.

Methods: Two microarrays of BCSCs and no-BCSCs were isolated from mammosphere-3D-cultured MCF-7 cells, differentially expressed lncRNAs (DELs) were screened out by Gene Expression Omnibus (GEO). Gene ontology enrichment analysis and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were also performed to analyze DELs features. Using the STRING database to analyze DELs interaction network module to further screen the hub lncRNAs related to tumor stemness and make functional annotations. The expressions of hub DELs were validated using data from The Cancer Genome Atlas database. In addition, the expression analysis and survival analysis were conducted using GEO was utilized to analyze DELs in TNBC using GEPIA database.

Results: A total of 143 aberrantly expressed lncRNAs in BCSCs were identified, and 25 lncRNAs were downregulated and 118 lncRNAs were upregulated compared to non-BCSCs. Up- and downregulated top 3 lncRNAs were selected and verified by RT-PCR. Notably, GO enrichment analysis and KEGG pathway analysis indicated that RNA transport, spliceosome, oxidative phosphorylation, NOD-like receptor signaling pathway, PI3K-Akt signaling pathway, and metabolic pathways may serve important roles in BCSCs. Additionally, the function loss assay indicated that ZGRF1 positively upregulated phenotype and biological functions of BCSCs in vitro. Collectively, our work establishes the lncRNAs signature in BCSCs and these findings assess us with evidence to explore further functionalities of lncRNAs in BCSCs and provide a novel therapeutic strategy for breast cancer.

Conclusion: Our work establishes the lncRNAs signature in BCSCs and these findings assess us with evidence to explore further functionalities of lncRNAs in BCSCs and provide a novel therapeutic strategy for breast cancer. ZGRF1 expression is upregulated in TNBC patients and has a poor prognosis, which can be promising biomarkers.

Keywords: ZGRF1; breast cancer stem cells; lncRNAs; triple-negative breast cancer.

Grants and funding

This work was funded by the National Natural Science Foundation of China (No. 81172522 and No. 81301858), the Suzhou science and technology project (No. SYS201508 and SYS201308) and the Jiangsu Natural Science Foundation Project (BK20181186).