Department of Stomatology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
J Cell Physiol. 2018 Dec;233(12):9447-9457. doi: 10.1002/jcp.26833. Epub 2018 Aug 22.
Aberrant expressions of microRNAs have been reported to be strongly associated with the progression and prognosis of various tumors, including oral squamous cell carcinoma (OSCC). Recent studies on miRNA expression profiling have suggested that microRNA-16 (miR-16) may be dysregulated in OSCC. However, the tumorigenic roles and mechanisms of miR-16 in OSCC are still largely unknown. In this study, we demonstrated that miR-16 was specifically downregulated in both OSCC patients and cancer cell lines. In addition, functional roles of miR-16 in vitro suggested that the miR-16 mimic inhibited cell proliferation and induced apoptosis, whereas miR-16 inhibitor displayed the opposite effects. Luciferase reporter assay and correlation analysis showed that AKT3 and BCL2L2 were directly targeted by miR-16 and were inversely expressed with miR-16 in OSCC. Moreover, restoration of AKT3 and BCL2L2 expression could partially reverse the cell proliferation inhibition and apoptosis induction caused by miR-16. In xenograft nude mice, miR-16 mimics decreased the expression of AKT3 and BCL2L2 and reduced the tumors volumes and weights, whereas the miR-16 inhibitor exhibited adverse effects in the derived xenografts. In conclusion, the findings suggested that miR-16 functions as a tumor suppressor miRNA to inhibit cell proliferation and induce apoptosis in OSCC through decreasing the oncogenes AKT3 and BCL2L2 and that miR-16 could be a potential therapeutic target for OSCC.
异常表达的 microRNAs 与多种肿瘤的发生和预后密切相关，包括口腔鳞状细胞癌（OSCC）。最近 microRNA 表达谱的研究表明，miR-16 在 OSCC 中可能失调。然而，miR-16 在 OSCC 中的致癌作用和机制仍知之甚少。在本研究中，我们证明 miR-16 在 OSCC 患者和癌细胞系中均特异性下调。此外，miR-16 在体外的功能作用表明，miR-16 模拟物抑制细胞增殖并诱导细胞凋亡，而 miR-16 抑制剂则显示出相反的效果。荧光素酶报告基因检测和相关性分析表明，AKT3 和 BCL2L2 是 miR-16 的直接靶基因，并且在 OSCC 中与 miR-16 呈负相关表达。此外，AKT3 和 BCL2L2 表达的恢复可以部分逆转 miR-16 引起的细胞增殖抑制和凋亡诱导。在异种移植裸鼠中，miR-16 模拟物降低了 AKT3 和 BCL2L2 的表达，减少了肿瘤体积和重量，而 miR-16 抑制剂在衍生的异种移植中表现出不良影响。总之，这些发现表明，miR-16 通过降低癌基因 AKT3 和 BCL2L2 的表达，作为一种肿瘤抑制 miRNA，在 OSCC 中抑制细胞增殖并诱导细胞凋亡，并且 miR-16 可能是 OSCC 的潜在治疗靶点。
