Department of Urology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 83301, Taiwan, ROC.
Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan, ROC.
Sci Rep. 2022 Apr 28;12(1):6955. doi: 10.1038/s41598-022-08091-6.
The role of miRNAs in cancer and their possible function as therapeutic agents are interesting and needed further investigation. The miR-26a-5p had been demonstrated as a tumor suppressor in various cancers. However, the importance of miR-26a-5p regulation in upper tract urothelial carcinoma (UTUC) remains unclear. Here, we aimed to explore the miR-26a-5p expression in UTUC tissues and to identify its regulatory targets and signal network involved in UTUC tumorigenesis. The miR-26a-5p expression was validated by quantitative real-time polymerase chain reaction (qPCR) using renal pelvis tissue samples from 22 patients who were diagnosed with UTUC and 64 cases of renal pelvis tissue microarray using in situ hybridization staining. BFTC-909 UTUC cells were used to examine the effects of miR-26a-5p genetic delivery on proliferation, migration and expression of epithelial-to-mesenchymal transition (EMT) markers. MiR-26a-5p was significantly down-regulated in UTUC tumors compared to adjacent normal tissue and was decreased with histological grades. Moreover, restoration of miR-26a-5p showed inhibition effects on proliferation and migration of BFTC-909 cells. In addition, miR-26a-5p delivery regulated the EMT marker expression and inhibited WNT5A/β-catenin signaling and expression of downstream molecules including NF-κB and MMP-9 in BFTC-909 cells. This study demonstrated that miR-26a-5p restoration may reverse EMT process and regulate WNT5A/β-catenin signaling in UTUC cells. Further studies warranted to explore the potential roles in biomarkers for diagnostics and prognosis, as well as novel therapeutics targets for UTUC treatment.
miRNAs 在癌症中的作用及其作为治疗剂的可能功能很有趣，需要进一步研究。miR-26a-5p 已被证明在多种癌症中是一种肿瘤抑制因子。然而，miR-26a-5p 在尿路上皮癌（UTUC）中的调控作用尚不清楚。在这里，我们旨在探讨 miR-26a-5p 在 UTUC 组织中的表达，并确定其在 UTUC 肿瘤发生中涉及的调节靶点和信号网络。通过定量实时聚合酶链反应（qPCR）使用 22 例诊断为 UTUC 的肾盂组织样本和 64 例肾盂组织微阵列原位杂交染色验证 miR-26a-5p 的表达。使用 BFTC-909 UTUC 细胞来检测 miR-26a-5p 遗传传递对增殖、迁移和上皮-间充质转化（EMT）标志物表达的影响。与相邻正常组织相比，miR-26a-5p 在 UTUC 肿瘤中显著下调，且随着组织学分级降低而减少。此外，miR-26a-5p 的恢复显示对 BFTC-909 细胞的增殖和迁移具有抑制作用。此外，miR-26a-5p 的传递调节 EMT 标志物的表达，并抑制 WNT5A/β-catenin 信号通路以及包括 NF-κB 和 MMP-9 在内的下游分子在 BFTC-909 细胞中的表达。本研究表明，miR-26a-5p 的恢复可能逆转 EMT 过程并调节 UTUC 细胞中的 WNT5A/β-catenin 信号通路。需要进一步研究以探讨其在诊断和预后的生物标志物中的潜在作用，以及作为 UTUC 治疗的新治疗靶点。
