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KMID : 1134120220250030193
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Journal of Breast Cancer
2022 Volume.25 No. 3 p.193 ~ p.206
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miR-638 Serves as a Biomarker of 5-Fluorouracil Sensitivity to Neoadjuvant Chemotherapy in Breast Cancer
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Wang Bin
Wang Kun
Yu Jian
Hao Xiao-Meng
Liu Yu-Lu
Xing Ai-Yan
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Abstract
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Purpose: Neoadjuvant chemotherapy (NAC) is widely used to treat breast cancer (BC). The prediction and evaluation of chemotherapy responses remains a significant challenge.
Methods: MicroRNAs (miRNAs) play a crucial role in cancer drug resistance. We used a miRNA microarray and identified that miR-638 is downregulated in chemoresistant cases. However, the exact role of miR-638 and the underlying mechanisms of chemoresistance remain unclear. Using real-time quantitative reverse transcription polymerase chain reaction, we found significant downregulation of miR-638 in chemoresistant patients compared with chemosensitive patients. To explore the function of miR-638, we overexpressed and inhibited miR-638 expression in MDA-MB-231 and MCF-7 cells by transfecting them with miR-638 mimics and miR-638 inhibitor, respectively. Cell proliferation and apoptosis were measured using MTS and flow cytometry, respectively. A minimal patient-derived xenograft (MiniPDX™) model was established to evaluate the chemosensitivity to different drugs.
Results: The results showed that cell proliferation decreased and cell apoptosis increased in cells transfected with the miR-638 mimic, and cell proliferation and apoptosis were reversed with transfection of miR-638 inhibitor compared with the control group. Among patients who received 5-fluorouracil (5-FU), miR-638 expression levels were lower in the chemoresistant group than in the chemosensitive group. The MiniPDX™ model showed that MDA-MB-231 cells overexpressing miR-638 were more susceptible to 5-FU treatment in vivo.
Conclusion: We provided evidence of acquired resistance to 5-FU caused by miR-638 deficiency. Alterations in miR-638 may be used with 5-FU chemotherapy during NAC for BC.
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KEYWORD
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Breast Neoplasms, Fluorouracil, MicroRNA-638, Neoadjuvant Therapy
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