Triple-negative breast cancer (TNBC) is a one of the subtypes of breast cancer which accounts for approximately 10–20% of all breast cancers. LncRNA XIST (XIST) is reported to be dysfunctional in numerous tumor types and is involved in the key pathways of cancer initiation, progression and metastasis. Thus, in the present study, we explored the detailed molecular mechanism of XIST in TNBC. XIST was down-regulated in TNBC tissues and cell lines. Overexpressed XIST inhibited cell proliferation, epithelial mesenchymal transition (EMT) and induced apoptosis in vitro as well as suppressed TNBC tumor growth in vivo . MicroRNA (miR)-454 was up-regulated in TNBC tissues and cell lines. Knockdown of miR-454 inhibited TNBC progression by suppressing cell proliferation, EMT and inducing cell apoptosis. Moreover, miR-454 was predicted and confirmed to be a target of XIST, and rescue assay indicated that overexpressed miR-454 could reverse XIST restoration mediated-anti-tumor effects on TNBC cells. In conclusion, XIST interacts with miR-454 to inhibit cells proliferation, EMT and induce apoptosis in TNBC, indicating a promising treatment strategy for TNBC patients.

中文翻译：

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LncRNA XIST与miR-454相互作用抑制细胞增殖、上皮间质转化并诱导三阴性乳腺癌细胞凋亡

三阴性乳腺癌 (TNBC) 是乳腺癌的一种亚型，约占所有乳腺癌的 10-20%。据报道，LncRNA XIST (XIST) 在多种肿瘤类型中功能失调，并参与癌症发生、进展和转移的关键途径。因此，在本研究中，我们探索了 XIST 在 TNBC 中的详细分子机制。XIST 在 TNBC 组织和细胞系中下调。过表达的 XIST 在体外抑制细胞增殖、上皮间充质转化 (EMT) 和诱导细胞凋亡，并在体内抑制 TNBC 肿瘤生长。MicroRNA (miR)-454 在 TNBC 组织和细胞系中上调。敲除 miR-454 通过抑制细胞增殖、EMT 和诱导细胞凋亡来抑制 TNBC 进展。而且，miR-454 被预测并证实是 XIST 的靶标，并且救援试验表明过表达的 miR-454 可以逆转 XIST 恢复介导的对 TNBC 细胞的抗肿瘤作用。总之，XIST 与 miR-454 相互作用以抑制 TNBC 中的细胞增殖、EMT 并诱导细胞凋亡，表明 TNBC 患者的治疗策略很有前景。