Department of Gastroenterological Surgery, Graduate School of Life Sciences, Kumamoto University, Kumamoto City, Kumamoto, Japan.
Department of Chemistry, Helwan University, Cairo, Egypt.
Ann Surg Oncol. 2021 Nov;28(12):7973-7982. doi: 10.1245/s10434-021-09778-2. Epub 2021 Apr 22.
MicroRNA (miRNA) expression abnormalities are implicated in tumor progression. Previous reports have indicated that microRNA-25 (miR-25) acts as a tumor suppressor or oncogene in diverse cancers. However, its molecular mechanisms in hepatocellular carcinoma (HCC) are still unclear. F-box and WD repeat domain 7 (Fbxw7) is a critical tumor suppressor and is one of the most important deregulated proteins of the ubiquitin-proteasome system in cancer. Our objective was to elucidate the role of miR-25 and Fbxw7 in HCC and to clarify the mechanism by which Fbxw7 is regulated.
Fbxw7 expression was estimated in 210 fixed paraffin-embedded HCC samples by immunohistochemistry, and miR-25 expression was evaluated in 142 frozen HCC tissue samples by quantitative real-time PCR. Oncogenic functions of miR-25 and its role in the regulation of Fbxw7 expression were assayed in vitro.
miR-25 was overexpressed in HCC tissue compared with adjacent normal tissue and significantly correlated with a poorer prognosis. Moreover, it was inversely correlated with Fbxw7 expression in HCC tissues. Furthermore, miR-25 inhibition significantly reduced the proliferation, migration, and invasion of HCC cells in vitro.
miR-25 may promote tumor progression in HCC patients by repression of Fbxw7 and could serve as a promising molecular target for HCC treatment.
微小 RNA(miRNA)表达异常与肿瘤进展有关。先前的报告表明,微小 RNA-25(miR-25)在多种癌症中作为肿瘤抑制因子或癌基因发挥作用。然而,其在肝细胞癌(HCC)中的分子机制尚不清楚。F-box 和 WD 重复结构域 7(Fbxw7)是一种重要的肿瘤抑制因子,是癌症中泛素-蛋白酶体系统最重要的失调蛋白之一。我们的目的是阐明 miR-25 和 Fbxw7 在 HCC 中的作用,并阐明 Fbxw7 调节的机制。
通过免疫组织化学法检测 210 例固定石蜡包埋 HCC 样本中的 Fbxw7 表达,通过实时定量 PCR 法检测 142 例冷冻 HCC 组织样本中的 miR-25 表达。在体外测定 miR-25 的致癌功能及其对 Fbxw7 表达的调控作用。
miR-25 在 HCC 组织中表达高于相邻正常组织,与预后不良显著相关。此外,它与 HCC 组织中 Fbxw7 的表达呈负相关。此外,miR-25 抑制显著降低了 HCC 细胞在体外的增殖、迁移和侵袭。
miR-25 可能通过抑制 Fbxw7 促进 HCC 患者的肿瘤进展,可作为 HCC 治疗的有前途的分子靶点。