Long non-coding RNA MIR100HG promotes the migration, invasion and proliferation of triple-negative breast cancer cells by targeting the miR-5590-3p/OTX1 axis

Fei-Yu Chen,Zhi-Yang Zhou,Ke-Jing Zhang,Shou-Man Wang,Jian Pang

doi:10.1186/s12935-020-01580-6

Abstract

BackgroundAs an aggressive subtype of breast cancer with a high risk of recurrence, triple-negative breast cancer (TNBC) lacks available treatment targets. LncRNA MIR100HG promotes cell proliferation in TNBC. However, few studies have investigated the molecular mechanism of MIR100HG in TNBC. Thus, additional in-depth investigations are needed to unravel its associated regulatory mechanism.MethodsMIR100HG and miR-5590-3p expression in TNBC tissue samples and cell lines was detected by RT-qPCR. Flow cytometry, transwell, wound-healing, CCK8 and colony formation assays were performed to analyse cell apoptosis, cell cycle, invasion, migration and proliferation. The protein expression of orthodenticle homeobox 1 (OTX1) and proteins in the ERK/MAPK signalling pathway were assessed by western blot analysis. Bioinformatics and luciferase assay were performed to predict and validate the interaction between MIR100HG and miR-5590-3p as well as OTX1 and miR-5590-3p. RNA immunoprecipitation (RIP) was used to detect the interaction between MIR100HG and miR-5590-3p. Subcutaneous tumour growth was observed in nude mice. Immunohistochemistry (IHC) analysis was used to assess OTX1 expression in tumour tissues.ResultsMIR100HG expression was upregulated, whereas that of miR-5590-3p was downregulated in TNBC. MIR100HG was shown to directly interact with miR-5590-3p. Furthermore, MIR100HG knockdown could promote TNBC cell apoptosis and cell cycle arrest in G0/G1 phase while inhibiting migration, invasion and proliferation. Furthermore, miR-5590-3p inhibition showed the opposite results and could reverse the effect of MIR100HG knockdown in TNBC cells. MiR-5590-3p downregulated the ERK/MAPK signalling pathway, suppressed the migration, invasion and proliferation of TNBC cells and promoted their apoptosis and cell cycle arrest in G0/G1 phase by targeting OTX1. In addition, MIR100HG knockdown inhibited OTX1 expression by upregulating miR-5590-3p in vivo, thereby inhibiting tumour growth.ConclusionsMIR100HG promotes the progression of TNBC by sponging miR-5590-3p, thereby upregulating OTX1, suggesting a new potential treatment target for TNBC.

Highlights

As an aggressive subtype of breast cancer with a high risk of recurrence, triple-negative breast cancer (TNBC) lacks available treatment targets
MIR100HG and miR‐5590‐3p are differentially expressed in TNBC tissues and cells MIR100HG and miR-5590-3p in 20 pairs of TNBC and adjacent normal tissues was assessed by RTqPCR (Fig. 1a)
MIR100HG knockdown inhibits the invasion and migration of TNBC cells by upregulating miR‐5590‐3p expression we investigated the molecular mechanism by which MIR100HG regulates the migration and invasion of TNBC cells

Summary

Introduction

As an aggressive subtype of breast cancer with a high risk of recurrence, triple-negative breast cancer (TNBC) lacks available treatment targets. As the most common malignancy in women, breast cancer has become the dominant cause of cancer-associated death and is divided into a variety of molecular subtypes, Chen et al Cancer Cell Int (2020) 20:508 among which TNBC is the most aggressive and has a high risk of recurrence [1, 2]. LncRNA MIR100HG takes part in cancer progression in both miRNA-independent and -dependent manners It can promote the migration and proliferation of laryngeal squamous cell carcinoma cells [11] and can function as oncogene in acute megakaryoblastic leukaemia [12]. The regulatory role of MIR100HG in promoting TNBC cell proliferation has been reported [13]. Additional efforts should be made to unravel its regulatory mechanism in greater depth

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Conclusion