AUTHOR=Tang Li , Chen Yuli , Chen Huanhuan , Jiang Pan , Yan Linping , Mo Dongping , Tang Xun , Yan Feng 

TITLE=DCST1-AS1 Promotes TGF-β-Induced Epithelial–Mesenchymal Transition and Enhances Chemoresistance in Triple-Negative Breast Cancer Cells via ANXA1

JOURNAL=Frontiers in Oncology

VOLUME=10

YEAR=2020

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.00280

DOI=10.3389/fonc.2020.00280

ISSN=2234-943X

ABSTRACT=<p>Triple-negative breast cancer (TNBC) is a highly metastatic breast cancer subtype, and the primary systemic treatment strategy involves conventional chemotherapy. DC-STAMP domain containing 1-antisense 1 (<italic>DCST1-AS1</italic>) is a long non-coding RNA that promotes TNBC migration and invasion. Studying the role of <italic>DCST1-AS1</italic> in promoting epithelial–mesenchymal transition (EMT) and chemoresistance will provide a new strategy for TNBC therapy. In the present study, we found that <italic>DCST1-AS1</italic> regulates the expression or secretion of EMT-related proteins E-cadherin, snail family zinc finger 1 (SNAI1), vimentin, matrix metallopeptidase 2 (MMP2), and matrix metallopeptidase 9 (MMP9). Interference with <italic>DCST1-AS1</italic> impaired TGF-β-induced TNBC cell invasion and migration. <italic>DCST1-AS1</italic> directly binds to ANXA1 in BT-549 cells and affects the expression of ANXA1. <italic>DCST1-AS1</italic> enhances TGF-β/Smad signaling in BT-549 cells through ANXA1 to promote EMT. The combination of <italic>DCST1-AS1</italic> and ANXA1 also contributes to enhancement of the resistance of BT-549 cells to doxorubicin and paclitaxel. In conclusion, <italic>DCST1-AS1</italic> promotes TGF-β-induced EMT and enhances chemoresistance in TNBC cells through ANXA1, and therefore represents a potentially promising target for metastatic breast cancer therapy.</p>