Department of Otorhinolaryngology (Head and Neck Surgery), Lihuili Hospital of Ningbo University, Ningbo University School of Medicine, Ningbo, 315040, China.
Med Oncol. 2012 Dec;29(4):2473-80. doi: 10.1007/s12032-011-0156-x. Epub 2012 Jan 14.
Survivin has been shown to be an ideal target for cancer gene therapy because of its strong antiapoptotic effect. MicroRNA-34a (miR-34a) can function as a tumor suppressor in some cancers through negative regulation of gene expression. However, the relationship between miR-34a and survivin in larynx squamous cell carcinoma (LSCC) has not been explored. The abundance of survivin mRNA and miR-34a in LSCC tissues were measured using quantitative real-time polymerase chain reaction. Their expression levels were analyzed and correlated with tumor differentiation, lymphatic metastasis, clinical stages, and survival rates. MiR-34a mimic was transfected using liposomes to increase its level in LSCC cancer cell line, Hep-2. The effects of miR-34a on survivin protein expression were tested using western blot analysis. Cell cycle analyses were performed using flow cytometry. The results showed that transfection of miR-34a mimic significantly suppressed cell proliferation with decreased survivin protein expression, but did not affect mRNA expression level. The results from LSCC tissue samples showed that miR-34a was downregulated, while survivin expression was upregulated. The miR-34a levels were negatively correlated with histologic differentiation and were positively correlated with survival rate. MiR-34a significantly suppressed cell proliferation by arresting cells at G0/G1 phase in Hep-2 cells. These results indicated that miR-34a may affect the occurrence of LSCC by targeting survivin.
Survivin 因其强大的抗凋亡作用而被证明是癌症基因治疗的理想靶点。MicroRNA-34a (miR-34a) 可以通过负向调节基因表达在某些癌症中发挥肿瘤抑制作用。然而,miR-34a 与喉鳞状细胞癌 (LSCC) 中的 survivin 之间的关系尚未得到探索。采用实时定量聚合酶链反应测量 LSCC 组织中 survivin mRNA 和 miR-34a 的丰度。分析它们的表达水平,并与肿瘤分化、淋巴转移、临床分期和生存率相关联。使用脂质体转染 miR-34a 模拟物以增加 LSCC 癌细胞系 Hep-2 中的 miR-34a 水平。使用 Western blot 分析测试 miR-34a 对 survivin 蛋白表达的影响。通过流式细胞术进行细胞周期分析。结果表明,转染 miR-34a 模拟物可显著抑制细胞增殖,降低 survivin 蛋白表达,但不影响 mRNA 表达水平。LSCC 组织样本的结果表明,miR-34a 下调,而 survivin 表达上调。miR-34a 水平与组织学分化呈负相关,与生存率呈正相关。miR-34a 可通过将 Hep-2 细胞阻滞在 G0/G1 期来显著抑制细胞增殖。这些结果表明,miR-34a 可能通过靶向 survivin 影响 LSCC 的发生。