Department of Otolaryngology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China.
Mol Med Rep. 2018 Apr;17(4):5283-5291. doi: 10.3892/mmr.2018.8523. Epub 2018 Jan 31.
MicroRNAs (miRNAs) have been reported to be associated with the modulation of tumor development, including alterations associated with the development of human laryngeal squamous cell carcinoma (LSCC). The present study was designed to investigate whether miRNA‑195 was associated with the pathophysiologic process of human LSCC and to identify its potential roles and underlying molecular mechanisms. To determine whether miRNA‑195 serves a role in LSCC, reverse transcription‑quantitative polymerase chain reaction was used to detect miRNA‑195 expression in LSCC tissues. The tumor‑suppressive effect of miRNA‑195 was determined by in vitro assays. Gain‑of‑function studies using miRNA‑195 mimics were performed to investigate cell viability, migration and invasion, and apoptosis in the AMC‑HN‑8 cell line. Western blotting was performed to reveal the molecular mechanisms of miRNA‑195 and its downstream signaling pathways in the LSCC AMC‑HN‑8 cell line. The present study demonstrated that miRNA‑195 is downregulated in primary LSCC tumors. Upregulating miRNA‑195 in vitro suppressed cell viability, migration and invasion in AMC‑HN‑8 cells. Overexpression of miRNA‑195 alone in AMC‑HN‑8 cells was sufficient to induce cell apoptosis, as identified by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. Compared with the high expression of miRNA‑195 in AMC‑HN‑8 cells, the expression levels of vascular endothelial growth factor receptor‑II protein and downstream signaling pathway proteins, which were associated with cell viability, migration, invasion and apoptosis, were markedly decreased compared with control or miRNA‑195 negative control treatment group. Together, these data suggest the therapeutic potential of miRNA‑195 in modulating cell growth, migration and apoptosis during the pathophysiological progression of LSCC and that miRNA‑195 may serve as a potential therapeutic target in human LSCC.
微小 RNA(miRNA)已被报道与肿瘤发展的调节有关,包括与人喉鳞状细胞癌(LSCC)发展相关的改变。本研究旨在探讨 miRNA-195 是否与人类 LSCC 的病理生理过程有关,并确定其潜在作用和潜在的分子机制。为了确定 miRNA-195 是否在 LSCC 中起作用,使用逆转录-定量聚合酶链反应检测 LSCC 组织中的 miRNA-195 表达。通过体外测定来确定 miRNA-195 的肿瘤抑制作用。使用 miRNA-195 模拟物进行功能获得研究,以研究 AMC-HN-8 细胞系中的细胞活力、迁移和侵袭以及细胞凋亡。通过 Western blot 分析来揭示 miRNA-195 及其在 LSCC AMC-HN-8 细胞系中的下游信号通路的分子机制。本研究表明,miRNA-195 在原发性 LSCC 肿瘤中下调。体外上调 miRNA-195 可抑制 AMC-HN-8 细胞的活力、迁移和侵袭。单独过表达 miRNA-195 足以诱导 AMC-HN-8 细胞的细胞凋亡,如末端脱氧核苷酸转移酶 dUTP 缺口末端标记法(TUNEL)检测所示。与 AMC-HN-8 细胞中 miRNA-195 的高表达相比,与细胞活力、迁移、侵袭和凋亡相关的血管内皮生长因子受体-2 蛋白和下游信号通路蛋白的表达水平明显低于对照组或 miRNA-195 阴性对照组。综上所述,这些数据表明 miRNA-195 具有在 LSCC 病理生理进展过程中调节细胞生长、迁移和凋亡的治疗潜力,并且 miRNA-195 可能是人类 LSCC 的潜在治疗靶点。