Department of Ophthalmology, The First People's Hospital of Shangqiu, Shangqiu, Henan 476100, P.R. China.
Department of Pathology, Xinxiang Medical University, Xinxiang, Henan 453000, P.R. China.
Int J Oncol. 2019 Mar;54(3):807-820. doi: 10.3892/ijo.2019.4689. Epub 2019 Jan 17.
Accumulating evidence has indicated that the dysregulation of microRNAs (miRNAs) is involved in the pathogenesis o retinoblastoma (RB); however, the potential role of miR‑98 in RB remains elusive. In the present study, it was demonstrated that miR‑98 is downregulated in RB tissues and cell lines, and its expression significantly associated with clinicopathological features, including differentiation, N classification and largest tumor base; patients with low miR‑98 expression levels exhibited significantly poorer overall survival. Overexpression of miR‑98 was suggested to suppress RB cell growth, migration and invasion. In addition, insulin‑like growth factor‑1 receptor (IGF1R), a well‑reported oncogene, was identified as a potential target of miR‑98 via a luciferase assay, reverse transcription‑quantitative polymerase chain reaction and western blotting. Correlation analysis revealed a significantly negative correlation between miR‑98 and IGF1R expression in tumor tissues (n=60). In addition, the results of the present study demonstrated that IGF1R function as an oncogene by promoting RB cell viability, migration and invasion. Furthermore, restoration of IGF1R was observed to reverse the anticancer effects of miR‑98 on RB cell viability, migration and invasion. Importantly, the findings of the present study indicated that miR‑98 suppressed RB cell growth and metastasis by inhibiting the IGF1R/k‑Ras/Raf/mitogen activated protein kinase kinase/extracellular signal‑regulated kinase signaling pathway. Collectively, the present study proposed that miR‑98 may serve as a novel prognostic biomarker and therapeutic target in the treatment of RB.
越来越多的证据表明，微小 RNA（miRNA）的失调参与了视网膜母细胞瘤（RB）的发病机制；然而，miR-98 在 RB 中的潜在作用仍不清楚。在本研究中，表明 miR-98 在 RB 组织和细胞系中下调，其表达与临床病理特征显著相关，包括分化、N 分类和最大肿瘤基底；miR-98 低表达水平的患者总生存率显著较差。过表达 miR-98 被认为可抑制 RB 细胞生长、迁移和侵袭。此外，通过荧光素酶报告基因检测、逆转录-定量聚合酶链反应和 Western blot 分析，胰岛素样生长因子-1 受体（IGF1R）被确定为 miR-98 的潜在靶基因，IGF1R 是一种有报道的癌基因。相关性分析显示 miR-98 和 IGF1R 在肿瘤组织（n=60）中的表达呈显著负相关。此外，本研究结果表明，IGF1R 通过促进 RB 细胞活力、迁移和侵袭来发挥癌基因的作用。此外，恢复 IGF1R 观察到逆转 miR-98 对 RB 细胞活力、迁移和侵袭的抗癌作用。重要的是，本研究的结果表明，miR-98 通过抑制 IGF1R/k-Ras/Raf/丝裂原激活蛋白激酶激酶/细胞外信号调节激酶信号通路抑制 RB 细胞的生长和转移。综上所述，本研究表明 miR-98 可能作为治疗 RB 的一种新的预后标志物和治疗靶点。
