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微小 RNA-34a 通过靶向抗凋亡基因生存素影响喉鳞状细胞癌的发生。

MicroRNA-34a affects the occurrence of laryngeal squamous cell carcinoma by targeting the antiapoptotic gene survivin.

机构信息

Department of Otorhinolaryngology (Head and Neck Surgery), Lihuili Hospital of Ningbo University, Ningbo University School of Medicine, Ningbo, 315040, China.

出版信息

Med Oncol. 2012 Dec;29(4):2473-80. doi: 10.1007/s12032-011-0156-x. Epub 2012 Jan 14.

Abstract

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.

摘要

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。

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