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 SUM159PTR and MDA-MB-231R 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-231R 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.
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This study was partially supported by grants from the Major Project in Natural Science Research in Higher Education Institutions of Anhui Province, Grant/Award Number: 2023AH040393.
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YPW is the guarantor of integrity of the entire study and contributed to the statistical analysis; YPW, HYS contributed to the study concepts, manuscript editing; XDW contributed to the study design, literature research, manuscript review; ZYZ, HYS contributed to the definition of intellectual content; ZYZ, JG contributed to the experimental studies, manuscript preparation; JG, XDW contributed to the data acquisition; YPW, ZYZ contributed to the data analysis; All authors read and approved the final manuscript.
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11010_2023_4908_MOESM1_ESM.tiff
Figure S1 Knockdown of miR-524-5p increased the drug resistance of SUM159PT and MDA-MB-231. RT-qPCR to determine miR-524-5p expression in A SUM159PT and B MDA-MB-231 cells; Flow cytometry to assess apoptosis in C SUM159PT and D MDA-MB-231 cells with or without DOX/DXL treatment; CCK-8 to evaluate E SUM159PT and F MDA-MB-231 cell viability. The cellular experiments were repeated three times. Data were expressed as mean ± SD, and one-way ANOVA was utilized for comparisons among multiple groups, followed by Tukey’s test. *p < 0.05, **p < 0.01
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Wang, Y., Wang, X., Sun, H. et al. LncRNA MCM3AP-AS1 promotes chemoresistance in triple-negative breast cancer through the miR-524-5p/RBM39 axis. Mol Cell Biochem (2024). https://doi.org/10.1007/s11010-023-04908-8
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DOI: https://doi.org/10.1007/s11010-023-04908-8