Zheng Xu, Zhang Luyao, Feng Ying, Zhu Fan, Shi Jiangming, Feng Yang, Chen Qian, Shen Ruizhi
Department of Intensive Care Unit, Suzhou Hospital, Affiliated Hospital of Medical School, Nanjing University, Suzhou, China.
Department of Oncology, The Affiliated Suzhou Hospital of Nanjing Medical University, Suzhou Municipal Hospital, Gusu School, Nanjing Medical University, Suzhou, Jiangsu, China.
J Cancer. 2025 Jul 28;16(12):3589-3598. doi: 10.7150/jca.116946. eCollection 2025.
Increasingly evidence shows that the interaction between long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and their downstream target genes plays a pivotal role in the onset and progression of tumors, emerging as a focal point in tumor research. This study sought to assess the biological function of lncRNA SNHG15 and investigate the underlying mechanisms involved in SNHG15/miR-153-3p/KLF5 signal axis in breast cancer (BC). The expressions of SNHG15, miR-153-3p and KLF5 in human BC tissues and cell lines were detected by quantitative real-time PCR and/or western blot. To investigate the biological functions of SNHG15, we knocked it down in BC cells and observed its effects both and . The underlying mechanisms of competitive endogenous RNA (ceRNA) between SNHG15 and miR-153-3p were elucidated through bioinformatics analysis, dual-luciferase reporter assays and rescue experiments. SNHG15 expression was notably elevated in BC tissues and cell lines. Knockdown of SNHG15 significantly reduced the ability of proliferation, migration and invasion in BC cells. miR-153-3p was a direct target of SNHG15, while miR-153-3p mediated the expression of KLF5 in BC cell lines. In addition, the effect of SNHG15 downregulation on the biological behavior of BC cells can be offset by the inhibition of miR-153-3p. Mechanically, SNHG15 may act as the ceRNA of miR-153-3p, thereby regulating the expression of its target gene KLF5. SNHG15 promotes proliferation and metastasis by sponging miR-153-3p and regulates KLF5 expression, suggesting that SNHG15 may be a potential biomarker and therapeutic target for BC.
越来越多的证据表明，长链非编码RNA（lncRNAs）、微小RNA（miRNAs）及其下游靶基因之间的相互作用在肿瘤的发生和发展中起着关键作用，已成为肿瘤研究的一个焦点。本研究旨在评估lncRNA SNHG15的生物学功能，并探讨SNHG15/miR-153-3p/KLF5信号轴在乳腺癌（BC）中的潜在机制。通过定量实时PCR和/或蛋白质免疫印迹法检测人BC组织和细胞系中SNHG15、miR-153-3p和KLF5的表达。为了研究SNHG15的生物学功能，我们在BC细胞中敲低它，并观察其在[此处原文缺失部分内容]的影响。通过生物信息学分析、双荧光素酶报告基因检测和挽救实验阐明了SNHG15与miR-153-3p之间竞争性内源RNA（ceRNA）的潜在机制。SNHG15在BC组织和细胞系中的表达显著升高。敲低SNHG15显著降低了BC细胞的增殖、迁移和侵袭能力。miR-153-3p是SNHG15的直接靶标，而miR-153-3p介导了BC细胞系中KLF5的表达。此外，抑制miR-153-3p可抵消SNHG15下调对BC细胞生物学行为的影响。从机制上讲，SNHG15可能作为miR-153-3p的ceRNA，从而调节其靶基因KLF5的表达。SNHG15通过海绵吸附miR-153-3p促进增殖和转移并调节KLF5表达，表明SNHG15可能是BC的潜在生物标志物和治疗靶点。
