Qin Le, Zhang Yu, Lin Jie, Shentu Yangping, Xie Xiaoxiao
Department of Pediatric Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Department of Hematology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang 325000, P.R. China.
Oncol Rep. 2016 Dec;36(6):3325-3332. doi: 10.3892/or.2016.5139. Epub 2016 Sep 30.
MicroRNA-455 (miR-455) has been considered as a novel cancer-related miRNA and dysregulated expression frequently occurs in various human types of cancer. However, its clinical significance, its biological function and the underlying molecular signaling involved in hepatocellular carcinoma (HCC) remain to be elucidated. In the present study, we found that the expression level of miR-455 was significantly downregulated in both HCC tissues and cell lines. Low expression of miR-455 was significantly associated with poor prognostic features including multiple tumor nodes, high Edmondson‑Steiner grading, advanced tumor-node‑metastasis (TNM) stage and venous infiltration. In addition, our data revealed that miR-455 was a novel prognostic indicator for predicting the 5-year overall and disease-free survival of HCC patients. The gain- and loss-of-function studies revealed that miR-455 significantly suppressed migration and invasion of HCC cells in vitro. miR-455 was inversely correlated with runt-related transcription factor 2 (Runx2) expression in HCC samples. Moreover, we identified that miR-455 inversely regulated Runx2 expression in HCC cells. In this investigation, Runx2 was found to be a direct downstream target of miR-455. Evidently, alteration in Runx2 expression suppressed the effect of miR-455 on HCC cell migration and invasion. In conclusion, our data demonstrated that miR-455 promotes HCC growth by targeting Runx2 and can potentially be regarded as a novel prognostic indicator and valuable therapeutic strategy for HCC.
微小RNA-455(miR-455)被认为是一种新型的癌症相关微小RNA,其表达失调在多种人类癌症类型中频繁出现。然而,其在肝细胞癌(HCC)中的临床意义、生物学功能及潜在分子信号通路仍有待阐明。在本研究中,我们发现miR-455在HCC组织和细胞系中的表达水平均显著下调。miR-455低表达与不良预后特征显著相关,包括多个肿瘤结节、高Edmondson-Steiner分级、晚期肿瘤-淋巴结-转移(TNM)分期及静脉浸润。此外,我们的数据显示miR-455是预测HCC患者5年总生存率和无病生存率的新型预后指标。功能获得和缺失研究表明,miR-455在体外显著抑制HCC细胞的迁移和侵袭。在HCC样本中,miR-455与 runt相关转录因子2(Runx2)表达呈负相关。此外,我们确定miR-455在HCC细胞中反向调节Runx2表达。在本研究中,发现Runx2是miR-455的直接下游靶点。显然,Runx2表达的改变抑制了miR-455对HCC细胞迁移和侵袭的影响。总之,我们的数据表明miR-455通过靶向Runx2促进HCC生长,并且有可能被视为HCC的新型预后指标和有价值的治疗策略。