miR-638 Serves as a Biomarker of 5-Fluorouracil Sensitivity to Neoadjuvant Chemotherapy in Breast Cancer

Bin Wang; Kun Wang; Jian Yu; Xiao-meng Hao; Yu-lu Liu; Ai-Yan Xing

doi:10.4048/jbc.2022.25.e24

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자료유형: 학술저널

저자정보: Bin Wang (Department of General Surgery The First Affiliated Hospital of Shandong First Medical University &a) Kun Wang (Department of General Surgery The First Affiliated Hospital of Shandong First Medical University &a) Jian Yu (Department of General Surgery The First Affiliated Hospital of Shandong First Medical University &a) Xiao-meng Hao (Department of Pathology Shandong University Qilu Hospital Jinan P.R. China.) Yu-lu Liu (Department of Pathology Shandong University Qilu Hospital Jinan P.R. China.) Ai-Yan Xing (Department of Pathology Shandong University Qilu Hospital Jinan P.R. China.)

저널정보: 한국유방암학회 Journal of Breast Cancer Journal of Breast Cancer Vol.25 No.3

발행연도: 2022.6

수록면: 193 - 206 (14page)

DOI: 10.4048/jbc.2022.25.e24

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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.

#Breast Neoplasms #Fluorouracil #MicroRNA-638 #Neoadjuvant Therapy

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Bin Wang

소속기관 Department of General Surgery The First Affiliated Hospital of Shandong First Medical University &a