Zhao Zhiguo, Gao Dan, Ma Tie, Zhang Liping
Department of Oral and Maxillofacial Surgery, Shengjing Hospital of China Medical University, Shenyang, P.R.China.
Department of Clinical Laboratory, Shengjing Hospital of China Medical University, Shenyang, P.R.China.
Aging (Albany NY). 2019 Feb 8;11(3):921-932. doi: 10.18632/aging.101791.
MicroRNAs (miRNAs) serve as regulatory factors in both healthy tissue and various cancers. Here, we used an miRNA microarray to screen for miRNAs differentially expressed between HNSCC and adjacent epithelial tissue. Among these, levels of miR-141 were significantly reduced in HNSCC tissues. Expression levels of epidermal growth factor receptor (EGFR) were enhanced in tissues with low miR-141 expression but were reduced by miR-141 overexpression, and there was a significant negative correlation between EGFR and miR-141 levels in HNSCC tissues ( < 0.01). Luciferase assays confirmed that miR-141 targeted EGFR mRNA. , miR-141 inhibited the proliferation and migration of Cal-27 and FaDu HNSCC cells with corresponding decreases in CDK4 and MMP2. miR-141 also enhanced the incidence of apoptosis among the cells with a corresponding decrease in bcl-2. In BALB/c mice injected with FaDu HNSCC cells, miR-141 mitigated hepatic metastasis and inhibited expression of EGFR, CDK4, bcl-2 and MMP2. These results suggest that miR-141 functions as a tumor suppressor in HNSCC and that it suppresses tumor growth and metastasis by suppressing EGFR signaling. MiR-141 thus appears to be a potentially useful therapeutic target in the treatment of HNSCC.
微小RNA(miRNA)在健康组织和各种癌症中均发挥着调控作用。在此,我们使用miRNA微阵列筛选在头颈部鳞状细胞癌(HNSCC)与相邻上皮组织之间差异表达的miRNA。其中,miR-141在HNSCC组织中的水平显著降低。在miR-141低表达的组织中表皮生长因子受体(EGFR)的表达水平升高,但miR-141过表达则使其降低,且在HNSCC组织中EGFR与miR-141水平之间存在显著负相关(<0.01)。荧光素酶测定证实miR-141靶向EGFR mRNA。此外,miR-141抑制了Cal-27和FaDu HNSCC细胞的增殖和迁移,同时CDK4和MMP2相应减少。miR-141还增加了细胞凋亡发生率,同时bcl-2相应减少。在注射了FaDu HNSCC细胞的BALB/c小鼠中,miR-141减轻了肝转移并抑制了EGFR、CDK4、bcl-2和MMP2的表达。这些结果表明,miR-141在HNSCC中作为肿瘤抑制因子发挥作用,并且通过抑制EGFR信号传导来抑制肿瘤生长和转移。因此,miR-141似乎是治疗HNSCC的一个潜在有用的治疗靶点。