Long noncoding RNA (lncRNA) small nucleolar RNA host gene 1 (SNHG1) plays a positive role in the progression of human malignant tumors. However, the molecular mechanism of SNHG1 remains elusive in breast cancer. LncRNA SNHG1 was upregulated and had a positive relationship with poor prognosis according to bioinformatics analysis in pan-cancer including breast cancer. Silencing SNHG1 inhibited tumorigenesis in breast cancer both in vitro and in vivo. Mechanistically, SNHG1 functioned as a competing endogenous RNA (ceRNA) to promote TERT expression by sponging miR-18b-5p in breast cancer. miR-18b-5p acted as a tumor repressor in breast cancer. Moreover, the combination of SNHG1 knockdown and TERT inhibitor administration showed a synergistic inhibitory effect on breast cancer growth in vivo. Finally, E2F1 as a transcription factor, binding to SNHG1 promoter and enhanced SNHG1 transcription in breast cancer. Our results provide a comprehensive understanding of the oncogenic mechanism of lncRNA SNHG1 in breast cancer. Importantly, we identified a novel E2F1–SNHG1–miR-18b-5p–TERT axis, which may be a potential therapeutic target for breast cancer. Our results also provided a potential treatment for breast cancer when knockdown SNHG1 and TERT inhibitor administration simultaneously.

中文翻译：

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长链非编码 RNA SNHG1 通过海绵化 miR-18b-5p 在乳腺癌中促进 TERT 表达

长链非编码 RNA (lncRNA) 小核仁 RNA 宿主基因 1 (SNHG1) 在人类恶性肿瘤的进展中发挥积极作用。然而，SNHG1 在乳腺癌中的分子机制仍然难以捉摸。根据生物信息学分析，lncRNA SNHG1 在包括乳腺癌在内的泛癌中上调并与不良预后呈正相关。沉默 SNHG1 在体外和体内均抑制乳腺癌的肿瘤发生。从机制上讲，SNHG1 作为一种竞争性内源性 RNA (ceRNA)，通过在乳腺癌中海绵化 miR-18b-5p 来促进 TERT 表达。miR-18b-5p 在乳腺癌中充当肿瘤抑制因子。此外，SNHG1 敲低和 TERT 抑制剂给药的组合显示出对体内乳腺癌生长的协同抑制作用。最后，E2F1作为转录因子，与 SNHG1 启动子结合并增强乳腺癌中的 SNHG1 转录。我们的研究结果全面了解了 lncRNA SNHG1 在乳腺癌中的致癌机制。重要的是，我们发现了一个新的 E2F1–SNHG1–miR-18b-5p–TERT 轴，它可能是乳腺癌的潜在治疗靶点。我们的结果还提供了一种潜在的乳腺癌治疗方法，即同时使用敲低 SNHG1 和 TERT 抑制剂。