State Key Laboratory of Proteomics, Genetic Laboratory of Development and Diseases, Institute of Biotechnology, Beijing, PR China.
Int J Biol Sci. 2011 May 5;7(5):567-74. doi: 10.7150/ijbs.7.567.
Accumulating evidence has shown that miRNAs are aberrantly expressed in human gastric cancer and crucial to tumorigenesis. Herein, we identified the role of miR-148a in gastric cell proliferation. miR-148a knockdown inhibited cell proliferation in gastric cancer cell lines. Conversely, miR-148a overexpression promoted cell proliferation and cell cycle progression. p27, a key inhibitor of cell cycle, was verified as the target of miR-148a, indicating miR-148a might downregulate p27 expression to promote gastric cell proliferation. Moreover, we confirmed that miR-148a expression was frequently and dramatically downregulated in human advanced gastric cancer tissues, and observed a good inverse correlation between miR-148a and p27 expression in tumor samples. Thus, our results demonstrated that miR-148a downregulation might exert some sort of antagonistic function in cell proliferation, rather than promote cell proliferation in gastric cancer.
越来越多的证据表明,miRNAs 在人类胃癌中表达异常,对肿瘤发生至关重要。在此,我们确定了 miR-148a 在胃细胞增殖中的作用。miR-148a 敲低抑制胃癌细胞系中的细胞增殖。相反,miR-148a 过表达促进细胞增殖和细胞周期进程。p27 是细胞周期的关键抑制剂,被验证为 miR-148a 的靶标,表明 miR-148a 可能下调 p27 的表达以促进胃细胞增殖。此外,我们证实 miR-148a 在人类晚期胃癌组织中频繁且显著下调,并在肿瘤样本中观察到 miR-148a 与 p27 表达之间存在良好的负相关关系。因此,我们的结果表明,miR-148a 的下调可能在细胞增殖中发挥某种拮抗作用,而不是促进胃癌中的细胞增殖。