Zhang Chuanlei, Chen Xiaoqi, Chen Xinju, Wang Xinting, Ji Aiying, Jiang Lifeng, Sang Feng, Li Fucheng
Department of Digestive Diseases, The First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou, People's Republic of China.
Department of Chinese Traditional and Western Medicine, Henan Cancer Hospital, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou, People's Republic of China.
Onco Targets Ther. 2016 Jun 15;9:3555-63. doi: 10.2147/OTT.S105736. eCollection 2016.
miR-135a was downregulated in the majority of human primary gastric cancer (GC) tissues and GC cell lines. Kinesin family member C1 (KIFC1) was significantly upregulated in GC tissues and cell lines and promoted GC development and progression. We searched for miR-135a targets by using MiRanda, TargetScan, and PicTar tools, and found that KIFC1 was a potential target of miR-135a. Based on these findings, we speculated that miR-135a might target KIFC1 to inhibit GC growth. We determined the expression of miR-135a and KIFC1 by quantitative real-time polymerase chain reaction and Western blot assays, respectively, and found downregulation of miR-135a and upregulation of KIFC1 in GC tissues and cell lines. Cell proliferation and apoptosis assays showed that knockdown of KIFC1 inhibited proliferation and promoted apoptosis of GC cells, and miR-135a mimics had similar effects on GC cell proliferation and apoptosis. Furthermore, we verified that KIFC1 was a direct target of miR-135a, which confirmed our speculation that the functional effect of miR-135a on GC cells, at least, in part, depends on KIFC1. These findings suggest that miR-135a has an important role in the suppression of GC and presents a novel mechanism of miRNA-mediated KIFC1 expression in cancer cells.
在大多数人类原发性胃癌(GC)组织和GC细胞系中,miR-135a表达下调。驱动蛋白家族成员C1(KIFC1)在GC组织和细胞系中显著上调,并促进GC的发生和进展。我们使用MiRanda、TargetScan和PicTar工具搜索miR-135a的靶标,发现KIFC1是miR-135a的潜在靶标。基于这些发现,我们推测miR-135a可能靶向KIFC1以抑制GC生长。我们分别通过定量实时聚合酶链反应和蛋白质免疫印迹分析确定了miR-135a和KIFC1的表达,发现在GC组织和细胞系中miR-135a下调而KIFC1上调。细胞增殖和凋亡分析表明,敲低KIFC1可抑制GC细胞的增殖并促进其凋亡,miR-135a模拟物对GC细胞增殖和凋亡具有类似作用。此外,我们证实KIFC1是miR-135a的直接靶标,这证实了我们的推测,即miR-135a对GC细胞的功能作用至少部分取决于KIFC1。这些发现表明,miR-135a在抑制GC中具有重要作用,并揭示了miRNA介导癌细胞中KIFC1表达的新机制。