Background/Objectives: Schlafen12 (SLFN12) is an intermediate human Schlafen protein shown to correlate with survivability in triple-negative breast cancer (TNBC). SLFN12 causes differential expressions of significant cancer genes, but how they change in response to chemotherapy remains unknown. Our aim is to identify the effect of chemotherapy on genes that improve TNBC outcomes and other SLFN family members following SLFN12 knockout or overexpression. Methods: We overexpressed SLFN12 using a lentiviral vector and knocked out SLFN12 (AdvShSLFN12) using a hairpin adenovirus in MDA-MB-231 TNBC cells. Cells were treated with camptothecin, paclitaxel, zoledronic acid, or carboplatin to evaluate the SLFN12 signature cancer genes associated with improved TNBC outcomes using qPCR. Additionally, cells were treated alone and in combination with AdvShSLFN12, IFN-α2 (known SLFN12 stimulator), carboplatin, and paclitaxel. After treatment, the viable cell numbers were analyzed utilizing a colorimetric crystal violet assay for cell viability. Results: The SLFN family and SLFN12 cancer signature gene mRNA expressions were analyzed by RT-qPCR. Treating SLFN12-overexpressing TNBC cells with chemotherapy agents resulted in the differential expressions of eight cancer-related genes. Notably, GJB3 was downregulated following treatment with each chemotherapeutic drug. Inducing SLFN12 with IFN-α2 resulted in decreased cell viability and increased SLFN12 mRNA levels following treatment with paclitaxel or carboplatin. Conclusions: These results suggest that SLFN12 overexpression significantly affects the expressions of genes driving phenotypic changes in response to chemotherapy and influences additional SLFN family members following IFN-α2 treatment. This may contribute to improving the survival of patients with SLFN12 overexpression. Additionally, patient SLFN12 levels can be used as a factor when pursuing personalized chemotherapy treatments.
背景/目的：Schlafen12（SLFN12）是一种人类中间型Schlafen蛋白，已被证实与三阴性乳腺癌（TNBC）患者的生存率相关。SLFN12可引起关键癌症基因的差异表达，但这些基因如何响应化疗仍不清楚。本研究旨在明确化疗对改善TNBC预后的基因及其他SLFN家族成员在SLFN12敲除或过表达后的影响。方法：我们在MDA-MB-231三阴性乳腺癌细胞中通过慢病毒载体过表达SLFN12，并利用发夹腺病毒敲除SLFN12（AdvShSLFN12）。采用喜树碱、紫杉醇、唑来膦酸或卡铂处理细胞，通过qPCR评估与TNBC预后改善相关的SLFN12特征性癌症基因。此外，细胞分别单独或联合使用AdvShSLFN12、IFN-α2（已知的SLFN12激活剂）、卡铂和紫杉醇进行处理。处理后通过比色结晶紫染色法分析活细胞数量以评估细胞活力。结果：通过RT-qPCR分析SLFN家族及SLFN12癌症特征基因的mRNA表达。化疗药物处理过表达SLFN12的TNBC细胞后，八个癌症相关基因呈现差异表达。值得注意的是，GJB3在所有化疗药物治疗后均出现下调。IFN-α2诱导SLFN12表达后，紫杉醇或卡铂处理组的细胞活力下降，同时SLFN12 mRNA水平升高。结论：这些结果表明，SLFN12过表达显著影响驱动化疗应答表型变化的基因表达，并在IFN-α2处理后影响其他SLFN家族成员。这可能有助于改善SLFN12过表达患者的生存状况。此外，患者SLFN12水平可作为实施个体化化疗方案的参考因素。
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