Characterization of ceRNA network to reveal potential prognostic biomarkers in triple-negative breast cancer.

Xiang Song,Zhaoyun Liu,Qi Liu,Chao Zhang,Zhiyong Yu,Kewen He

doi:10.7717/peerj.7522

Abstract

Triple-negative breast cancer (TNBC) is a particular subtype of breast malignant tumor with poorer prognosis than other molecular subtypes. Previous studies have demonstrated that some abnormal expression of non-coding RNAs including microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were closely related to tumor cell proliferation, apoptosis, invasion, migration and drug sensitivity. However, the role of non-coding RNAs in the pathogenesis of TNBC is still unclear. In order to characterize the molecular mechanism of non-coding RNAs in TNBC, we downloaded RNA data and miRNA data from the cancer genome atlas database. We successfully identified 686 message RNAs (mRNAs), 26 miRNAs and 50 lncRNAs as key molecules for high risk of TNBC. Then, we hypothesized that the lncRNA–miRNA–mRNA regulatory axis positively correlates with TNBC and constructed a competitive endogenous RNA (ceRNA) network of TNBC. Our series of analyses has shown that five molecules (TERT, TRIML2, PHBP4, mir-1-3p, mir-133a-3p) were significantly associated with the prognosis of TNBC, and there is a prognostic ceRNA sub-network between those molecules. We mapped the Kaplan–Meier curve of RNA on the sub-network and also suggested that the expression level of the selected RNA is related to the survival rate of breast cancer. Reverse transcription-quantitative polymerase chain reaction showed that the expression level of TRIML2 in TNBC cells was higher than normal. In general, our findings have implications for predicting metastasis, predicting prognosis and discovering new therapeutic targets for TNBC.

Highlights

The incidence rate of breast cancer ranks first among those of female malignant tumors (Ferlay et al, 2015; Siegel, Miller & Jemal, 2017)
The criteria for screening data are as follows: (1) histopathological diagnosis is breast cancer; (2) screening for patients with loss of estrogen receptor (ER), progesterone receptor (PR) and HER2 expression in immunohistochemistry according to the diagnostic criteria of Triple-negative breast cancer (TNBC); (3) pathology in patient information the staging and follow-up data should be complete; (4) the selected patients did not suffer from other types of malignant tumors
There were 51 differentially expressed miRNAs between early and control groups, and 42 ones between advanced and control groups. Information about these DE-message RNAs (mRNAs), DE-long non-coding RNAs (lncRNAs), DE-miRNAs were placed in Supplemental Material 1

Summary

Introduction

The incidence rate of breast cancer ranks first among those of female malignant tumors (Ferlay et al, 2015; Siegel, Miller & Jemal, 2017). Triple-negative breast cancer (TNBC), as an important subtype of breast cancer, has stronger invasion, higher recurrence and metastasis rates, shorter survival time and more refractory treatment than those of non-TNBC due to negativities of estrogen receptor (ER), progesterone receptor (PR) and epidermal growth factor receptor 2 (HER2). It is of great significance to clarify the molecular biological mechanisms for the onset and progression of TNBC for predicting metastasis, determining prognosis and developing innovative therapies

Methods

Results

Discussion

Conclusion