Zhang Li-Ming, Ju Hou-Yu, Wu Yun-Teng, Guo Wei, Mao Lu, Ma Hai-Long, Xia Wei-Ya, Hu Jing-Zhou, Ren Guo-Xin
Department of Oral and Maxillofacial-Head and Neck Oncology, Ninth People's Hospital, School of Medicine, Shanghai Jiao Tong University Shanghai, China.
Shanghai Key Laboratory of Stomatology and Shanghai Research Institute of Stomatology, National Clinical Research Center for Oral Diseases Shanghai, China.
Am J Cancer Res. 2018 Nov 1;8(11):2296-2310. eCollection 2018.
ANRIL (CDKN2B antisense RNA 1, CDKN2B-AS1) is involved in the progression of various cancers. However, its role in head and neck squamous cell carcinoma (HNSCC) remains unclear. In this study, we found that ANRIL expression was upregulated in HNSCC and correlated with tumor progression. Further functional analysis showed that knockdown of ANRIL significantly inhibited proliferation in vivo and in vitro. ANRIL functioned as a ceRNA (competing endogenous RNAs) for miR-125a-3p and upregulated FGFR1 (fibroblast growth factor receptor-1), which could promote tumor growth. Moreover, we confirmed that ANRIL promoted HNSCC activity via FGFR1 with a FGFR1 inhibitor in vivo and in vitro. Thus, it could be concluded that ANRIL promoted the progression of HNSCC via miR-125a-3p/FGFR1/MAPK signaling, which might provide a new target for the diagnosis and treatment of HNSCC.
ANRIL(细胞周期蛋白依赖性激酶2B反义RNA1,CDKN2B-AS1)参与多种癌症的进展。然而,其在头颈部鳞状细胞癌(HNSCC)中的作用仍不清楚。在本研究中,我们发现HNSCC中ANRIL表达上调,并与肿瘤进展相关。进一步的功能分析表明,敲低ANRIL可显著抑制体内外增殖。ANRIL作为miR-125a-3p的竞争性内源性RNA(ceRNA)发挥作用,并上调成纤维细胞生长因子受体1(FGFR1),后者可促进肿瘤生长。此外,我们在体内外使用FGFR1抑制剂证实,ANRIL通过FGFR1促进HNSCC活性。因此,可以得出结论,ANRIL通过miR-125a-3p/FGFR1/丝裂原活化蛋白激酶(MAPK)信号通路促进HNSCC进展,这可能为HNSCC的诊断和治疗提供新的靶点。