LncRNA MCM3AP-AS1 promotes chemoresistance in triple-negative breast cancer through the miR-524-5p/RBM39 axis

Yueping Wang; Xuedong Wang; Haiyi Sun; Ziyun Zhang; Juan Gu

doi:10.1007/s11010-023-04908-8

LncRNA MCM3AP-AS1 promotes chemoresistance in triple-negative breast cancer through the miR-524-5p/RBM39 axis

Mol Cell Biochem. 2024 Mar 12. doi: 10.1007/s11010-023-04908-8. Online ahead of print.

Authors

Yueping Wang^{1

2}, Xuedong Wang³, Haiyi Sun⁴, Ziyun Zhang¹, Juan Gu¹

Affiliations

¹ Department of Medical Laboratory Science, Anhui No. 2 Provincial People's Hospital, 1868 #Dangshan Road, North 2nd Ring, Hefei, 230041, Anhui, China.
² Department of Molecular and Cellular Biology, University of Connecticut, Storrs, CT, 06269, USA.
³ Department of Medical Laboratory Science, Anhui No. 2 Provincial People's Hospital, 1868 #Dangshan Road, North 2nd Ring, Hefei, 230041, Anhui, China. wxd729@126.com.
⁴ School of Clinical Medicine, Anhui Medical University, Hefei, 230032, Anhui, China.

PMID: 38472681
DOI: 10.1007/s11010-023-04908-8

Abstract

Triple-negative breast cancer (TNBC) is the most lethal subtype of BC, with unfavorable treatment outcomes. Evidence suggests the engagement of lncRNA MCM3AP-AS1 in BC development. This study investigated the action of MCM3AP-AS1 in chemoresistance of TNBC cells. Drug-resistant TNBC cell lines SUM159PT^R and MDA-MB-231^R were constructed by exposure to increasing concentrations of doxorubicin/docetaxel (DOX/DXL). MCM3AP-AS1 and miR-524-5p expression levels were determined by RT-qPCR. RNA binding motif 39 (RBM39) level was measured using Western blot. Cell viability and apoptosis were assessed by CCK-8 assay and flow cytometry. The targeted binding of miR-524-5p with MCM3AP-AS1 or RBM39 was predicted by ECORI database and validated by dual-luciferase assays. The gain-and-loss of function assays were conducted in cells to investigate the interactions among MCM3AP-AS1, miR-524-5p, and RBM39. TNBC xenograft mouse models were established through subcutaneous injection of MCM3AP-AS1-silencing MDA-MB-231^R cells and intraperitoneally administrated with DOX/DXL to verify the role of MCM3AP-AS1 in vivo. MCM3AP-AS1 was upregulated in drug-resistant TNBC cells, and MCM3AP-AS1 silencing could sensitize drug-resistant TNBC cells to chemotherapeutic drugs by promoting apoptosis. MCM3AP-AS1 targeted miR-524-5p. After DOX/DXL treatment, miR-524-5p inhibition partially reversed the effect of MCM3AP-AS1 silencing on inhibiting chemoresistance and promoting apoptosis of drug-resistant TNBC cells. miR-524-5p targeted RBM39. Silencing MCM3AP-AS1 promoted apoptosis via the miR-524-5p/RBM39 axis, thereby enhancing chemosensitivity of drug-resistant TNBC cells. MCM3AP-AS1 knockdown upregulated miR-524-5p, downregulated RBM39, and restrained tumor development in vivo. MCM3AP-AS1 silencing potentiates apoptosis of drug-resistant TNBC cells by upregulating miR-524-5p and downregulating RBM39, thereby suppressing chemoresistance in TNBC.

Keywords: Apoptosis; Chemoresistance; Doxorubicin/docetaxel; MCM3AP-AS1; RNA binding motif 39; Triple-negative breast cancer; ceRNA; miR-524-5p.