三阴性乳腺癌（TNBC）是一种高度侵袭性亚型，由于其增殖和转移率高而预后差。最近，已经认识到硫化氢（H2S）作为一种新型气体信使，在包括癌症在内的各种病理生理过程中发挥重要作用。我们在此展示，外源性H2S通过体外抑制TNBC癌细胞的增殖、迁移和侵袭，同时在TNBC小鼠模型中也减少了癌症恶性程度。为了调查H2S在TNBC抗癌作用的潜在机制，我们进行了转录组测序和生物信息学分析。2121个差异表达基因（DEGs）被揭示出来，并主要富集在细胞周期和DNA复制途径。进一步的分析揭示了外源性H2S处理后替代剪接的变化。蛋白质互作网络分析（PPI）被执行，鉴定出了276个差异表达基因中富集在细胞周期和DNA复制途径中的458个相互作用。我们通过PPI网络分析确定了七个中心基因（MCM3、MCM4、MCM5、MCM6、CDC6、CDC45和GINS2），在临床人类乳腺癌中上调，但在H2S处理后下调。基于选择的中心基因，我们开发了一个模型，预测外源性H2S主要通过延迟DNA复制发挥它的抗TNBC作用。我们的发现表明，外源性H2S在TNBC中具有潜在的治疗作用，并可能通过DNA复制和细胞周期途径发挥其治疗潜力。版权所有©2023作者。Elsevier Masson SAS出版。保留所有权利。

Triple negative breast cancer (TNBC) is a highly aggressive subtype with a poor prognosis due to its high rates of proliferation and metastasis. Recently, hydrogen sulfide (H2S) has been recognized as a novel gasotransmitter that plays a significant role in various pathological processes, including cancer. Here, we show that exogenous H2S inhibited TNBC cancer cell proliferation, migration and invasion in vitro, and also decreased cancer malignances in the mouse model of TNBC. To investigate the underlying mechanisms of H2S's anti-cancer effects in TNBC, we performed transcriptome sequencing and bioinformatic analyses. 2121 differentially expressed genes (DEGs) were revealed, and mainly enriched in cell cycle and DNA replication pathways. Further analysis revealed changes in alternative splicing after exogenous H2S treatment. Protein-protein interaction (PPI) network analysis was performed, which identified 458 interactions among 276 DEGs enriched in cell cycle and DNA replication pathways.We identified seven hub genes (MCM3, MCM4, MCM5, MCM6, CDC6, CDC45, and GINS2) through PPI network analysis, which were up-regulated in clinical human breast cancer but down-regulated after H2S treatment. Based on the hub genes selected, we developed a model predicting that exogenous H2S mainly exerts its anti-TNBC role by delaying DNA replication. Our findings suggest that exogenous H2S has potential as a therapeutic agent in TNBC and may exert its therapeutic potential through DNA replication and the cell cycle pathway.Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.