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

• Published in: Gene 2023-04, Vol.860, p.147230-147230, Article 147230
• Main Authors: Wei, Xinyu, Tao, Shuang, Mao, Huilan, Zhu, Haitao, Mao, Lingyu, Pei, Wenhao, Shi, Xiuru, Shi, Yingxiang, Zhang, Shiwen, Wu, Yulun, Wei, Ke, Wang, Jing, Pang, Siyan, Wang, Wenrui, Chen, Changjie, Yang, Qingling
• Format: Article
• Language: English
• Subjects: Animals; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - pathology; Cell Line, Tumor; Cell Movement - genetics; Cell Proliferation - genetics; CXC chemokine 12; Drug Resistance, Neoplasm; Exosomes; Female; Gene Expression Regulation, Neoplastic; Humans; lncRNA-rich transcription factor 1; Mice; MicroRNAs - genetics; MicroRNAs - metabolism; Paclitaxel - pharmacology; Paclitaxel resistance; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Tumor Microenvironment - genetics
• ISSN: 0378-1119; 1879-0038
• DOI: 10.1016/j.gene.2023.147230

•Exosomal lncRNA NEAT1 induces paclitaxel resistance in breast cancer cells.•lncRNA NEAT1 affects paclitaxel treatment resistance by binding miR-133b.•miR-133b promotes the sensitivity of cells to paclitaxel by targeting CXCL12.•NEAT1 silencing decreases paclitaxel resistance and tumour growth in vivo. The lncRNA nuclear paraspeckle assembly transcript 1 (lncRNA NEAT1) has been associated with the development, 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.