# Loss of miR-122 promotes cell migration and poor prognosis in triple-negative breast cancer treated by neoadjuvant chemotherapy

## TL;DR

Low levels of miR-122 in triple-negative breast cancer are linked to faster cancer return after treatment and increased cell movement.

## Contribution

This study reveals miR-122 loss promotes migration and poor outcomes in TNBC after chemotherapy by modulating BORIS expression.

## Key findings

- Low miR-122 levels in TNBC patients correlate with tumor recurrence after neoadjuvant chemotherapy.
- miR-122 inhibits cell migration and BORIS expression in TNBC cells.
- BORIS promotes a metastatic-related gene expression profile in miR-122-deficient TNBC tumors.

## Abstract

MicroRNAs (miRNAs) are short non-coding RNAs that regulate gene expression post-transcriptionally. miR-122 is abnormally expressed in breast cancer, functioning as both a tumor suppressor and oncomiR, however, its role in triple-negative breast cancer (TNBC) remains unclear.

In this study we investigate the molecular mechanism of miR-122 in TNBC patients undergoing neoadjuvant chemotherapy (NAC).

We analyzed the expression of miR-122 and its clinical association in TNBC patients from TCGA and KM-plotter datasets. Functional analysis was performed by modulating miR-122 levels in TNBC cells through antagomiR transfections for knockdown assays, and mimic-miR-122 assays, followed by RT-qPCR, immunoblotting, cell viability and migration assays.

Downregulation of miR-122 in TNBC patients is associated with tumor recurrence but not with pathologic complete response after NAC. Low miR-122 levels in rapid-relapse TNBC patients activate a gene co-expression network enriched in genes linked to migration, invasion, and cell differentiation. Among these, DNA-binding protein BORIS was identified as a target of miR-122. Overexpression of miR-122 inhibited cell migration and BORIS expression. Additionally, BORIS promoted a gene expression profile related to cell differentiation and cytoskeletal components in TNBC tumors deficient of miR-122.

The loss of miR-122 in TNBC tumors is associated with rapid relapse after chemotherapy in patients and allows cell migration by promoting a metastatic-related transcriptomic landscape, including positive modulation of BORIS expression.

The online version contains supplementary material available at 10.1007/s12094-025-04082-x.