Exosomal lncRNA NEAT1 induces paclitaxel resistance in breast cancer cells and promotes cell migration by targeting miR-133b

The lncRNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) has been associated with the devel-opment, metastasis and drug resistance of breast cancer (BC). However, the mechanisms underlying NEAT1-induced paclitaxel resistance in the microenvironment of BC remain unclear. In this study, NEAT1 expression was found to be high in paclitaxel-resistant BC cells (SKBR3/PR cells) and exosomes derived from these cells. NEAT1 promoted the migration of BC cells and their resistance to paclitaxel, whereas its downregulation reduced the drug resistance. In addition, downregulation of NEAT1 decreased the migration and proliferation of BC cells by inhibiting the expression of CXCL12 by reducing the adsorption of miR-133b. Furthermore, inhibition of miR-133b reversed the interference of NEAT1 and CXCL12 in paclitaxel resistance, migration and proliferation of BC cells. Knockdown of NEAT1 in a xenograft-bearing mouse model remarkably inhibited cancer progression and improved the response to paclitaxel. Altogether, this study revealed that SKBR3/PR cell-derived exosomal lncRNA NEAT1 can induce paclitaxel resistance and cell migration and growth in the tumour microenvironment of BC and may serve as a new target for the clinical treatment of BC.

Automated summary

This study found that lncRNA NEAT1 is highly expressed in BC cells and exosomes. NEAT1 promotes migration and paclitaxel resistance in BC cells, while downregulation of NEAT1 reduces drug resistance. In addition, downregulation of NEAT1 decreases migration and proliferation of BC cells by inhibiting CXCL12 expression and reducing miR-133b adsorption. This study reveals that exosomal lncRNA NEAT1 derived from SKBR3/PR cells in the tumor microenvironment can induce paclitaxel resistance, cell migration, and growth, and may serve as a new target for clinical treatment of BC.