Xu Ying, Xiao Hongmei, Li Zhongwen, Li Jing
Department of Oncology, The Second Affiliated Hospital of Zunyi Medical University, Zunyi, China.
School of Anesthesiology, Affiliated Hospital of Guizhou Medical University, Guiyang, China.
Sci Rep. 2025 Jul 1;15(1):21911. doi: 10.1038/s41598-025-06808-x.
Breast cancer (BC) has become a severe threat to women, which has imposed excessive pressure on society. LncRNAs play a crucial role in the occurrence and development of BC. This study aimed to evaluate the lncRNA SIAH2 antisense RNA 1 (SIAH2-AS1) role in the development and progression of BC and explore the mechanism of SIAH2-AS1 related Wnt signaling pathway in BC. Malignant and paracancer normal breast tissue samples were obtained from patients who underwent surgery at the Second Affiliated Hospital of Zunyi Medical University. Subsequently, quantitative RT-PCR (qRT-PCR) was performed with these acquired tissue samples to evaluate the concentrations of SIAH2-AS1. Furthermore, CCK-8 assays, colony formation, wound healing, and transwell were performed to investigate the cell proliferation, migration, and invasion respectively. Western blotting was eventually performed for the investigation of proteins and EMT-related markers in the Wnt/β-catenin signaling pathway. The expression of SIAH2-AS1 was up-regulated in cancer tissues and cells. Cell proliferation, colony formation, invasiveness, and migration are significantly reduced by silencing SIAH2-AS1. Moreover, E-cadherin expression in BC cells was increased, whereas N-cadherin and vimentin expression was decreased, when SIAH2-AS1 was eliminated from the cells. Additionally, the Wnt/β-catenin signaling pathways cyclin D1 and C-myc proteins were also significantly downregulated in BC cells when SIAH2-AS1 was knocked out. Our study confirms that SIAH2-AS1 activates the Wnt/β-catenin pathway and has an oncogenic activity that promotes the prognosis of BC, suggesting that SIAH2-AS1 may be a potential drug target for BC. The development of small - molecule inhibitors capable of specifically targeting SIAH2 - AS1 to target and modify the SIAH2 - AS1 gene in cancer cells may offer a novel strategy for clinical treatment. Keywords: breast cancer; cell proliferation; cell migration; Long noncoding RNA; Wnt signaling pathway.
乳腺癌(BC)已成为对女性的严重威胁,给社会带来了巨大压力。长链非编码RNA(lncRNAs)在BC的发生和发展中起着关键作用。本研究旨在评估长链非编码RNA SIAH2反义RNA 1(SIAH2-AS1)在BC发生发展中的作用,并探讨SIAH2-AS1相关Wnt信号通路在BC中的作用机制。从遵义医科大学第二附属医院接受手术的患者中获取恶性和癌旁正常乳腺组织样本。随后,对这些获取的组织样本进行定量逆转录-聚合酶链反应(qRT-PCR),以评估SIAH2-AS1的浓度。此外,分别进行CCK-8检测、集落形成实验、伤口愈合实验和Transwell实验,以研究细胞增殖、迁移和侵袭情况。最后进行蛋白质免疫印迹法,以研究Wnt/β-连环蛋白信号通路中的蛋白质和上皮-间质转化(EMT)相关标志物。SIAH2-AS1在癌组织和细胞中的表达上调。沉默SIAH2-AS1可显著降低细胞增殖、集落形成、侵袭和迁移能力。此外,当从细胞中消除SIAH2-AS1时,BC细胞中E-钙黏蛋白的表达增加,而N-钙黏蛋白和波形蛋白的表达降低。此外,当敲除SIAH2-AS1时,BC细胞中Wnt/β-连环蛋白信号通路的细胞周期蛋白D1和C-myc蛋白也显著下调。我们的研究证实,SIAH2-AS1激活Wnt/β-连环蛋白通路,并具有促进BC预后的致癌活性,这表明SIAH2-AS1可能是BC的潜在药物靶点。开发能够特异性靶向SIAH2-AS1以在癌细胞中靶向和修饰SIAH2-AS1基因的小分子抑制剂,可能为临床治疗提供一种新策略。关键词:乳腺癌;细胞增殖;细胞迁移;长链非编码RNA;Wnt信号通路