Long non-coding RNA LRRC75A-AS1 facilitates triple negative breast cancer cell proliferation and invasion via functioning as a ceRNA to modulate BAALC

Sijie Li,Zhiru Zhang,Hongyao Jia,Di Wu

doi:10.1038/s41419-020-02821-2

Abstract

As a common female malignancy, triple-negative breast cancer (TNBC) is the most serious subtype in breast cancer (BC). BAALC binder of MAP3K1 and KLF4 (BAALC) is a common oncogene in acute myelocytic leukemia (AML). We sought to explore the role of BAALC in TNBC. In this study, BAALC was significantly upregulated in TNBC tissues and cells. Then, the results of functional assays disclosed that BAALC facilitated cell proliferation, invasion, and epithelial–mesenchymal transition (EMT) processes, but repressed cell apoptosis in TNBC. Next, miR-380–3p was identified as the upstream of BAALC in TNBC cells. Moreover, LRRC75A-AS1 (also named small nucleolar RNA host gene 29: SNHG29) was verified to act as the sponge of miR-380–3p to elevate BAALC expression in TNBC. Besides, LRRC75A-AS1 could negatively regulate miR-380–3p but positively regulate BAALC expression. Finally, rescue assays elucidated that LRRC75A-AS1 facilitated cell proliferation, invasion, and EMT processes in TNBC by targeting miR-380–3p/BAALC pathway. Taken together, our study revealed a novel ceRNA network of LRRC75A-AS1/miR-380–3p/BAALC in accelerating TNBC development, indicating new promising targets for TNBC treatment.

Highlights

As one of the most common female malignancy, breast cancer (BC) is the major cause of female fatality globally, accounting for around 6.6% of global cancer fatality rate[1]
To explore the role of BAALC in triple-negative breast cancer (TNBC), firstly, qRTPCR analysis confirmed that BAALC was an abnormally upregulated gene in TNBC tissues compared with paired controls (Fig. S1A)
Kaplan–Meier analysis illustrated that high BAALC expression was closely correlated with the poor prognosis of TNBC patients (Fig. S1B)

Summary

Introduction

As one of the most common female malignancy, breast cancer (BC) is the major cause of female fatality globally, accounting for around 6.6% of global cancer fatality rate[1]. BC is characterized by high heterogeneity and contains at least five subtypes: HER2 overexpressing, Luminal A, Luminal B, and triple-negative breast cancers (TNBC), which are generally divided into basal-like and claudinlow subtypes[2,3]. TNBC is featured by lacking the expression of estrogen receptors and progesterone receptors[4]. Chemotherapy is the most preferred treatment for TNBC patients[5]. Chinese herbal compound has been reported to function in BC6. Cornus officinalis could inhibit TNBC cell growth[7].

Methods

Results

Conclusion