Niu Jun-Tao, Zhang Li-Jun, Huang Yong-Wang, Li Chao, Jiang Ning, Niu Yuan-Jie
a Department of Otorhinolaryngology, Head and Neck Surgery, the Second Hospital, Tianjin Medical University, Tianjin, 300211, China.
b Basic Medical Institute, Tianjin Medical University, Tianjin, 300000, China.
Biochem Cell Biol. 2018 Dec;96(6):752-760. doi: 10.1139/bcb-2018-0047. Epub 2018 Jun 6.
MicroRNAs are critical regulators of the development and progression of laryngeal squamous cell carcinoma (LSCC). However, the role of microRNA-154 (miR-154) in the development and progression of LSCC has not been clarified. We found that down-regulated miR-154 expression in LSCC tissues was associated with poorer prognosis in LSCC patients. MiR-154 over-expression inhibited the proliferation, clonogenicity, and migration of LSCC cells and induced cell cycle arrest, which were reversed by miR-154 inhibition. MiR-154 targeted GALNT7 expression by reducing GALNT7-regulated luciferase activity in LSCC cells while up-regulating GALNT7 mRNA transcription in LSCC tissues and cells. GALNT7 silencing significantly attenuated the proliferation, clonogenicity, and migration of LSCC cells and induced cell cycle arrest. Finally, intravenous treatment with lentivirus for miR-154, but not scrambled control miRNA, significantly restrained the growth of implanted LSCC Hep-2 tumors and decreased the tumor mass by reducing GALNT7 expression in mice. Therefore, miR-154 may serve as a novel prognostic marker and therapeutic target for LSCC.
微小RNA是喉鳞状细胞癌(LSCC)发生和发展的关键调节因子。然而,微小RNA - 154(miR - 154)在LSCC发生和发展中的作用尚未阐明。我们发现,LSCC组织中miR - 154表达下调与LSCC患者预后较差相关。miR - 154过表达抑制了LSCC细胞的增殖、克隆形成能力和迁移,并诱导细胞周期停滞,而miR - 154抑制可逆转这些作用。miR - 154通过降低LSCC细胞中GALNT7调节的荧光素酶活性靶向GALNT7表达,同时上调LSCC组织和细胞中GALNT7 mRNA转录。GALNT7沉默显著减弱了LSCC细胞的增殖、克隆形成能力和迁移,并诱导细胞周期停滞。最后,用慢病毒对miR - 154而非乱序对照微小RNA进行静脉注射治疗,通过降低小鼠体内GALNT7表达,显著抑制了植入的LSCC Hep - 2肿瘤的生长并减小了肿瘤体积。因此,miR - 154可能作为LSCC的一种新型预后标志物和治疗靶点。