BACKGROUND Breast cancer stem cells (BCSCs) are typically seed cells of breast tumor that initiate and maintain tumor growth. MiR-7, as a cancer inhibitor, decreases the BCSC subset and inhibits tumor progression through mechanisms that remain unknown. METHODS We examined miR-7 expression in breast cancer and developed a BCSC-driven xenograft mouse model, to evaluate the effects of miR-7 overexpression on the decrease of the BCSC subset in vitro and in vivo. In addition, we determined how miR-7 decreased the BCSC subset by using the ALDEFLUOR, lentivirus infection, dual-luciferase reporter, and chromatin immunoprecipitation-PCR assays. RESULTS MiR-7 was expressed at low levels in breast cancer tissues compared with normal tissues, and overexpression of miR-7 directly inhibited lncRNA XIST, which mediates the transcriptional silencing of genes on the X chromosome, and reduced epithelium-specific antigen (ESA) expression by increasing miR-92b and inhibiting slug. Moreover, miR-7 suppressed CD44 and ESA by directly inhibiting the NF-κB subunit RELA and slug in breast cancer cell lines and in BCSC-driven xenografts, which confirmed the antitumor activity in mice injected with miR-7 agomir or stably infected with lenti-miR-7. CONCLUSIONS The findings from this study uncover the molecular mechanisms by which miR-7 inhibits XIST, modulates the miR-92b/Slug/ESA axis, and decreases the RELA and CD44 expression, resulting in a reduced BCSC subset and breast cancer growth inhibition. These findings suggest a potentially targeted treatment approach to breast cancer.

中文翻译：

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MiR-7通过抑制XIST调节miR-92b / Slug / ESA轴并抑制肿瘤生长来减少BCSC亚群。

背景技术乳腺癌干细胞（BCSC）通常是启动和维持肿瘤生长的乳腺癌的种子细胞。MiR-7，作为一种癌症抑制剂，通过未知的机制降低了BCSC子集并抑制了肿瘤的进展。方法我们检查了miR-7在乳腺癌中的表达，并建立了BCSC驱动的异种移植小鼠模型，以评估miR-7过表达对体内外BCSC子集减少的影响。此外，我们使用ALDEFLUOR，慢病毒感染，双重荧光素酶报告基因和染色质免疫沉淀PCR方法确定了miR-7如何降低BCSC亚群。结果与正常组织相比，乳腺癌组织中的miR-7表达水平较低，miR-7的过表达直接抑制了lncRNA XIST，介导X染色体上基因的转录沉默，并通过增加miR-92b和抑制子弹来降低上皮特异性抗原（ESA）的表达。而且，miR-7通过直接抑制乳腺癌细胞系和BCSC驱动的异种移植物中的NF-κB亚基RELA和来抑制CD44和ESA，这证实了在注射miR-7agomir或稳定感染慢病毒的小鼠中的抗肿瘤活性。 -miR-7。结论本研究的发现揭示了miR-7抑制XIST，调节miR-92b / Slug / ESA轴并降低RELA和CD44表达的分子机制，从而导致BCSC子集减少和乳腺癌生长抑制。这些发现暗示了潜在的针对乳腺癌的治疗方法。并通过增加miR-92b和抑制inhibit来降低上皮特异性抗原（ESA）的表达。而且，miR-7通过直接抑制乳腺癌细胞系和BCSC驱动的异种移植物中的NF-κB亚基RELA和来抑制CD44和ESA，这证实了在注射miR-7agomir或稳定感染慢病毒的小鼠中的抗肿瘤活性。 -miR-7。结论本研究的发现揭示了miR-7抑制XIST，调节miR-92b / Slug / ESA轴并降低RELA和CD44表达的分子机制，从而导致BCSC子集减少和乳腺癌生长抑制。这些发现暗示了潜在的针对乳腺癌的治疗方法。并通过增加miR-92b和抑制inhibit来降低上皮特异性抗原（ESA）的表达。而且，miR-7通过直接抑制乳腺癌细胞系和BCSC驱动的异种移植物中的NF-κB亚基RELA和来抑制CD44和ESA，这证实了在注射miR-7agomir或稳定感染慢病毒的小鼠中的抗肿瘤活性。 -miR-7。结论本研究的发现揭示了miR-7抑制XIST，调节miR-92b / Slug / ESA轴并降低RELA和CD44表达的分子机制，从而导致BCSC子集减少和乳腺癌生长抑制。这些发现暗示了潜在的针对乳腺癌的治疗方法。miR-7通过直接抑制乳腺癌细胞系和BCSC驱动的异种移植物中的NF-κB亚基RELA和来抑制CD44和ESA，这证实了注射miR-7 agomir或稳定感染lenti-miR的小鼠的抗肿瘤活性。 -7。结论本研究的发现揭示了miR-7抑制XIST，调节miR-92b / Slug / ESA轴并降低RELA和CD44表达的分子机制，从而导致BCSC子集减少和乳腺癌生长抑制。这些发现暗示了潜在的针对乳腺癌的治疗方法。miR-7通过直接抑制乳腺癌细胞系和BCSC驱动的异种移植物中的NF-κB亚基RELA和来抑制CD44和ESA，这证实了注射miR-7 agomir或稳定感染lenti-miR的小鼠的抗肿瘤活性。 -7。结论本研究的发现揭示了miR-7抑制XIST，调节miR-92b / Slug / ESA轴并降低RELA和CD44表达的分子机制，从而导致BCSC子集减少和乳腺癌生长抑制。这些发现暗示了潜在的针对乳腺癌的治疗方法。调节miR-92b / Slug / ESA轴，并降低RELA和CD44表达，从而导致BCSC子集减少和乳腺癌生长受到抑制。这些发现暗示了潜在的针对乳腺癌的治疗方法。调节miR-92b / Slug / ESA轴，并降低RELA和CD44表达，从而导致BCSC子集减少和乳腺癌生长受到抑制。这些发现暗示了潜在的针对乳腺癌的治疗方法。