miR-23a-3p 通过靶向 FGF2 抑制口腔鳞状细胞癌的细胞增殖,且与较好的预后相关:miR-23a-3p 通过靶向 FGF2 抑制口腔鳞状细胞癌的生长。
miR-23a-3p suppresses cell proliferation in oral squamous cell carcinomas by targeting FGF2 and correlates with a better prognosis: miR-23a-3p inhibits OSCC growth by targeting FGF2.
作者信息
Chen Fubo, Qi Shengcai, Zhang Xu, Wu Jinjin, Yang Xi, Wang Raorao
机构信息
Department of Stomatology, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200072, China.
Department of Oral & MaxillofacialeHead & Neck Oncology, Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, China; Shanghai Key Laboratory of Stomatology & Shanghai Research Institute of Stomatology, National Clinical Research Center of Stomatology, China.
出版信息
Pathol Res Pract. 2019 Apr;215(4):660-667. doi: 10.1016/j.prp.2018.12.021. Epub 2018 Dec 24.
Oral squamous cell carcinomas (OSCCs) are one of the most ubiquitous malignancies the world over, and are accompanied by a high mortality. microRNAs (miRNAs) have increasingly garnered attention with regards to the roles they play in initiation and progression of various kinds of cancers, including OSCC. It has been reported, that miR-23a-3p promotes the development of tumors for prostate cancer, gastric cancer and gliomas. The functions of miR-23a-3p in OSCC however, remain unclear. In this study, fibroblast growth factor 2 (FGF2) is revealed as a direct target of miR-23a-3p, based on luciferase assays and immunoblotting. The expression of miR-23a-3p and FGF2 were found to be significantly downregulated and upregulated in OSCC tissues respectively. This indicates a reverse correlation between miR-23a-3p and FGF2 levels. Using in vitro approaches we ascertained that miR-23a-3p might contribute to the inhibition of growth and inhibition through increasing apoptosis in OSCC cells; while an inhibitor of miR-23a-3p could reverse this effect. Examination of a clinical cohort of OSCC patients suggested that reduced expression of miR-23a-3p is correlated with more advanced cancerous stage and poorer differentiation of OSCC cell. Additionally, a survival analysis and the Cox-hazard regression model showed that higher levels of miR-23a-3p can be used reliably for prognosis of OSCC patients. This study indicates that miR-23a-3p might suppress tumor proliferation, invasion and promote apoptosis of OSCC by targeting FGF2. miR-23a-3p has the potential to be used as prognostic indicator, and could be exploited as a therapeutic reagent for OSCC in the future.
口腔鳞状细胞癌(OSCC)是全球最常见的恶性肿瘤之一,死亡率很高。微小RNA(miRNA)在包括OSCC在内的各种癌症的发生和发展中所起的作用越来越受到关注。据报道,miR-23a-3p促进前列腺癌、胃癌和神经胶质瘤的肿瘤发展。然而,miR-23a-3p在OSCC中的功能仍不清楚。在本研究中,基于荧光素酶测定和免疫印迹,成纤维细胞生长因子2(FGF2)被揭示为miR-23a-3p的直接靶点。发现miR-23a-3p和FGF2的表达在OSCC组织中分别显著下调和上调。这表明miR-23a-3p和FGF2水平呈负相关。我们通过体外实验确定,miR-23a-3p可能通过增加OSCC细胞凋亡来抑制其生长;而miR-23a-3p抑制剂可逆转这种作用。对一组OSCC患者的临床研究表明,miR-23a-3p表达降低与OSCC细胞更晚期的癌症阶段和更差的分化相关。此外,生存分析和Cox风险回归模型表明,较高水平的miR-23a-3p可可靠地用于OSCC患者的预后评估。本研究表明,miR-23a-3p可能通过靶向FGF2抑制OSCC的肿瘤增殖、侵袭并促进其凋亡。miR-23a-3p有潜力用作预后指标,并可能在未来被开发为OSCC的治疗试剂。