# LncRNA LEF1-AS1 exerts a carcinogenic effect in breast cancer by accelerating proliferation, metastasis, and epithelial-mesenchymal transition

**Authors:** Linna Kong, Jiaqi Liu, Huihui Zhang, Jun Chu

PMC · DOI: 10.1186/s41065-025-00613-2 · Hereditas · 2025-11-29

## TL;DR

This study shows that the lncRNA LEF1-AS1 promotes breast cancer by increasing cell proliferation, metastasis, and EMT through interactions with miR-328-5p and KLF16.

## Contribution

The novel contribution is identifying LEF1-AS1 as a carcinogenic lncRNA in breast cancer that acts as a sponge for miR-328-5p to regulate KLF16 expression.

## Key findings

- LEF1-AS1 is highly expressed in breast cancer tissues and cells.
- Downregulating LEF1-AS1 reduces proliferation, migration, and EMT in BRCA cells.
- LEF1-AS1 promotes cancer progression by sponging miR-328-5p and upregulating KLF16.

## Abstract

Breast cancer (BRCA) directly poses a threat to human life safety. This study aims to explore the role of lncRNA LEF1-AS1 in BRCA.

Firstly, the levels of LEF1-AS1 in tumor tissues and BRCA cells were detected by qRT-PCR. Furthermore, LEF1-AS1 was inhibited through cell transfection. Subsequently, the proliferation, apoptosis and migration abilities of the cells were detected using the CCK-8 assay, flow cytometry and Transwell assay. Meanwhile, the mRNA levels of epithelial-mesenchymal transition (EMT) markers were also measured. The targeting binding relationships between LEF1-AS1 and miR-328-5p, as well as between miR-328-5p and KLF16, were verified by dual luciferase reporter assays and RNA pull-down assays. Furthermore, the effects of co-regulating LEF1-AS1 and miR-328-5p and down-regulating KLF16 on tumor cells were further investigated.

In tumor tissues and BRCA cell lines, LEF1-AS1 is highly expressed. Downregulation of LEF1-AS1 inhibits the malignant proliferation of BRCA cells and reduces their migration ability. Moreover, the process of EMT is significantly inhibited. miR-328-5p is the downstream target of LEF1-AS1. Simultaneously inhibiting miR-328-5p and LEF1-AS1 weakens the anti-cancer effect resulting from LEF1-AS1 silencing. LEF1-AS1 mainly participates in tumor progression by acting as a sponge molecule for miR-328-5p. Inhibiting LEF1-AS1 leads to the downregulation of KLF16, while the inhibition of miR-328-5p leads to the upregulation of KLF16. Moreover, the downregulation of KLF16 will result in weakened proliferation and migration abilities of BRCA cells.

LEF1-AS1 increases the level of KLF16 by sponging miR-328-5p, thereby promoting the proliferation, metastasis and EMT of BRCA cells.

The online version contains supplementary material available at 10.1186/s41065-025-00613-2.

## Linked entities

- **Genes:** LEF1-AS1 (LEF1 antisense RNA 1) [NCBI Gene 641518], KLF16 (KLF transcription factor 16) [NCBI Gene 83855]
- **Diseases:** breast cancer (MONDO:0004989)

## Full-text entities

- **Genes:** LEF1-AS1 (LEF1 antisense RNA 1) [NCBI Gene 641518] {aka LEF1NAT}
- **Diseases:** carcinogenic (MESH:D011230), metastasis (MESH:D009362), breast cancer (MESH:D001943)

## Full text

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## Figures

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Source: https://tomesphere.com/paper/PMC12771952