Tsai Ming-Ming, Wang Chia-Siu, Tsai Chung-Ying, Chen Cheng-Yi, Chi Hsiang-Cheng, Tseng Yi-Hsin, Chung Pei-Jung, Lin Yang-Hsiang, Chung I-Hsiao, Chen Ching-Ying, Lin Kwang-Huei
Department of Nursing, Chang-Gung University of Science and Technology, Taoyuan 333, Taiwan.
Department of General Surgery, Chang Gung Memorial Hospital at Chiayi, Chiayi 613, Taiwan.
Cancer Lett. 2014 Sep 1;351(2):222-31. doi: 10.1016/j.canlet.2014.06.004. Epub 2014 Jun 13.
MicroRNAs (miRNAs) play an important role to contribute carcinogenesis. The aim of the current study was to identify useful biomarkers from miRNAs. Differential miRNA profiles were analyzed using the miRNA qRT-PCR-based assay. Two of the most upregulated miRNAs were selected and validated. The miR-196a/-196b levels were significantly increased in gastric cancer (GC) tissues (n=109). Overexpression of miR-196a/-196b was significantly associated with tumor progression and poorer 5-year survival outcomes. Overexpression of miR-196a/-196b enhances GC cell migration and invasion. Further, radixin was identified as a target gene of miR-196a/-196b. Elevated miR-196a/-196b expression in GC cells led to reduced radixin protein levels and vice versa. Notably, an inverse correlation between miR-196a/-196b and radixin mRNA and protein expression was observed in GC tissues with in situ hybridization and immunohistochemistry analyses. Together, miR-196a/-196b inhibitory oligonucleotides or overexpression of the radixin may thus have therapeutic potential in suppressing GC metastasis.
微小RNA（miRNA）在肿瘤发生过程中发挥着重要作用。本研究的目的是从miRNA中鉴定出有用的生物标志物。使用基于miRNA qRT-PCR的检测方法分析差异miRNA谱。选择并验证了两个上调最为明显的miRNA。在胃癌（GC）组织（n = 109）中，miR-196a/-196b的水平显著升高。miR-196a/-196b的过表达与肿瘤进展及较差的5年生存结果显著相关。miR-196a/-196b的过表达增强了GC细胞的迁移和侵袭能力。此外，根蛋白被鉴定为miR-196a/-196b的靶基因。GC细胞中miR-196a/-196b表达升高导致根蛋白水平降低，反之亦然。值得注意的是，通过原位杂交和免疫组织化学分析在GC组织中观察到miR-196a/-196b与根蛋白mRNA及蛋白表达呈负相关。因此，miR-196a/-196b抑制性寡核苷酸或根蛋白的过表达在抑制GC转移方面可能具有治疗潜力。
