LSD1 inhibits the invasion and migration of breast cancer through exosomes

Sep 21, 2026

Uploaded by Levi

Metastasis accounts for nearly 90% of breast cancer deaths, yet the mechanisms that link LSD1 to tumor spread remain a key focus. LSD1, a histone demethylase, was tested by using breast cancer cells treated with MCF7 and T47D exosomes in which LSD1 was knocked down. Reduced LSD1 decreased miR-1290 expression and enhanced invasion and migration. Database analysis of miR-1290 targets identified NAT1, and expression regulation was validated, connecting epigenetic control to exosomal miRNA signaling and metastatic behavior.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages13

Reading Time33 min

AccessFree to download

Abstract

Background: LSD1, metastasis, and EMT

Exosomes in tumor microenvironment

miR-1290 and NAT1 in breast cancer

Present study and approach

Methods

Cells culture

[www. nature.com/scientificreports](www. nature.com/scientificreports) OPEN LSD1 inhibits the invasion and migration of breast cancer through exosomes Nan Zhang, Zhongyu Chen, Benkai Xin, Yueru Shi, Yutong Yao, Jingtong Yang, Xiaoyu Wang & Xin Hu * Metastasis accounts for almost 90% of breast cancer-related fatalities, making it frequent malignancy and the main reason of tumor mortality globally among women. LSD1 is a histone demethylase, which plays an important role in breast cancer. In order to explore the effect of LSD1 on invasion and migration of breast cancer, we treated breast cancer cells with MCF7 and T47D exosomes knocked down by LSD1, and the invasion and migration of breast cancer cells were significantly enhanced. This phenomenon indicates that LSD1 can inhibit the invasion and migration of breast cancer cells. miR- 1290 expression was downregulated in LSD1 knockdown MCF7 exosomes. By analyzing the database of miR-1290 target gene NAT1, we verified that miR-1290 could regulate the expression of NAT1 . These data provide fresh insights into the biology of breast cancer therapy by demonstrating how the epigenetic factor LSD1 stimulates the breast cancer cells’ invasion and migration via controlling exosomal miRNA. Keywords LSD1, Exosome, miR-1290 In women, the commonest cancer is breast cancer. It will represent 32% of all new cancer cases in the US in 2024 and increase at a pace of 0.6% annually1. One-quarter of all cancer cases and one-sixth of all cancer-related deaths among women globally are caused by breast cancer2. Although breast cancer’s 5-year relative survival rate is now 90%, metastasis reduces survival chances to about 25% . Some increase in survival is noticed (from 75% for patients diagnosed in the mid-1970s to 90% for patients diagnosed between 2011 and 2017)3,4. Understanding the processes underlying breast cancer metastasis is crucial since it may lead to novel approaches to the disease’s treatment. It was not until the discovery of the histone lysine specific demethylase 1 (LSD1) that there was a renewed awareness of the fact that LSD1-mediated histone demethylation is a gradual, highly coordinated process. Lysine specific demethylase 1 (LSD1) removes methyl groups from monomethylated lysines on histone H3 and from dimethyllysine (H3K4me1/me2)5–7. Breast cancer cells’ type and the stage of differentiation in which it is discovered determine the processes, including invasive metastasis and maintenance of breast cancer cell growth, in which LSD1 is involved8. It has been shown that LSD1 and SIN3A/HDAC complex synergistically inhibit the expression of a series of proto-oncogenes, such as CASP7, TGFB2, p21, etc. The LSD1 and SIN3A complexes are required for growth, epithelial characterisation, and the maintenance of drug sensitivity in breast cancer epithelial cells MCF7 . And knockdown of LSD1 and SIN3A leads to increased invasion and migration of MDAMB-231 cells.9. Moreover, earlier research has demonstrated that the binding of the LSD1/CoREST complex to the luminal-specific transcription factor GATA3 regulates luminal breast cancer cells, MCF7 invasion and migration and prevents tumor metastasis in mice with spontaneous breast cancer6, 10. According to certain theories, cancer cells may be able to undergo an epithelial-mesenchymal transition (EMT) to separate from their primary tumor and enter the vasculature11. Epithelial cells are regulated by gene expression, modifying the expression of cytoskeletal and adhesion proteins as well as cell morphology to exhibit more invasive and migrating characteristics. Ultimately, epithelial cells transform into more motile mesenchymal cells, which are important for development and wound healing as well as unique characteristics of primary tumor formation and metastasis12. Exosomes are a type of extracellular vesicle that can have a diameter of 40–200 nm (or 30–150 nm). They are created when the cell membrane fuses with a multivesicular body13

FAQs

How does LSD1 affect breast cancer invasion and migration in this study?

LSD1 knockdown in exosomes significantly enhances the invasion and migration of breast cancer cells, indicating that LSD1 normally inhibits these processes.

What role does miR-1290 play after LSD1 knockdown?

miR-1290 expression is downregulated in LSD1 knockdown MCF7 exosomes, and miR-1290 is shown to regulate NAT1 expression.

What is the proposed mechanism linking LSD1, exosomes, and metastasis?

The study proposes that LSD1 stimulates breast cancer invasion and migration by controlling exosomal miRNA signaling, specifically via miR-1290 regulation of NAT1.

Sep 21, 2026

Uploaded by Levi