Liu Shurong, Zhang Lu, Yang Yue, Wang Lijuan, Jiang Nan, Li Jiaqiu, Zhang Maoze
Department of Oncology, Sunshine Union Hospital, Weifang, 261205, Shandong, China.
Department of Oncology, Affiliated Hospital of Shandong Second Medical University, School of Clinical Medicine, Shandong Second Medical University, Weifang, 261031, Shandong, China.
Med Oncol. 2025 Jun 30;42(8):299. doi: 10.1007/s12032-025-02841-y.
MIR17HG plays a significant role in malignancies. Here, we explore its oncogenic roles across cancers. We further revealed the upstream and downstream regulatory mechanisms of MIR17HG in colorectal cancer. Through bioinformatics analysis, we found that 23 tumor types presented higher MIR17HG expression levels than normal tissues did, and 11 tumor types presented lower MIR17HG expression levels. MIR17HG expression is closely related to tumor stage and prognosis. Single-cell sequencing data analysis revealed that MIR17HG is highly expressed in the tumor microenvironment. MIR17HG expression is correlated with a cold immune microenvironment, including immune scores, immune cell infiltration and immune checkpoint gene expression. More importantly, patients with high MIR17HG expression are inclined to have worse immunotherapy effects. Targeting MIR17HG could weaken SIRT1-mediated cell survival in colorectal cancer. Many sensitive drugs are screened out for the SIRT1 protein by sensitivity analysis and virtual screening. Notably, the transcription factor HSF1 stimulates acetyltransferase P300-mediated enhancer activity in the MIR17HG promoter region, thereby activating MIR17HG transcription. Furthermore, clinical and mouse samples revealed the co-expression of the HSF1/SIRT1 axis in colorectal cancer. Overall, MIR17HG has the potential to be a bona fide biomarker for tumor diagnosis and predicting immunotherapy efficacy. Targeting the HSF1/MIR17HG/SIRT1 axis may be helpful for the treatment of colorectal cancer. We identify HSF1-mediated enhancer activity as a novel driver of MIR17HG overexpression, promoting SIRT1-dependent colorectal cancer progression.
MIR17HG在恶性肿瘤中发挥着重要作用。在此，我们探讨其在各种癌症中的致癌作用。我们进一步揭示了MIR17HG在结直肠癌中的上下游调控机制。通过生物信息学分析，我们发现23种肿瘤类型的MIR17HG表达水平高于正常组织，11种肿瘤类型的MIR17HG表达水平较低。MIR17HG表达与肿瘤分期和预后密切相关。单细胞测序数据分析显示，MIR17HG在肿瘤微环境中高表达。MIR17HG表达与冷免疫微环境相关，包括免疫评分、免疫细胞浸润和免疫检查点基因表达。更重要的是，MIR17HG高表达的患者倾向于有较差的免疫治疗效果。靶向MIR17HG可削弱结直肠癌中SIRT1介导的细胞存活。通过敏感性分析和虚拟筛选，筛选出许多针对SIRT1蛋白的敏感药物。值得注意的是，转录因子HSF1刺激乙酰转移酶P300介导的MIR17HG启动子区域的增强子活性，从而激活MIR17HG转录。此外，临床和小鼠样本显示结直肠癌中存在HSF1/SIRT1轴的共表达。总体而言，MIR17HG有潜力成为肿瘤诊断和预测免疫治疗疗效的真正生物标志物。靶向HSF1/MIR17HG/SIRT1轴可能有助于结直肠癌的治疗。我们确定HSF介导的增强子活性是MIR17HG过表达的新驱动因素，促进SIRT1依赖性结直肠癌进展。
