KITLG is a novel target of miR-34c that is associated with the inhibition of growth and invasion in colorectal cancer cells
KITLG is a novel target of miR-34c that is associated with the inhibition of growth and invasion in colorectal cancer cells
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KITLG 是 miR-34c 的新靶标，与抑制结直肠癌细胞的生长和侵袭有关
DOI：
10.1111/jcmm.12368
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发表时间：
2014-10-01
影响因子：
5.3
通讯作者：
Zhou, De-shan
中科院分区：
文献类型：
--
作者：
Yang, Shu;Li, Wen-shuai;Zhou, De-shan
MiR-34c被认为是一种有效的肿瘤抑制因子，因为它对与肿瘤发生和转移密切相关的多个靶标mrna进行负调控。在本研究中，我们证明了miR-34c的一个新靶点KITLG，它与结直肠癌（CRC）有关。首先，我们发现miR-34c与KITLG mRNA在CRC细胞系（包括HT-29、HCT-116、SW480和SW620）中的表达水平呈显著负相关。计算机分析预测了KITLG mRNA的3非翻译区（3UTR）中miR-34c的推定结合位点。双荧光素酶报告基因实验进一步证实KITLG是miR-34c的直接靶点。然后，用表达miR-34c或miR-34c特异性抑制剂的慢病毒感染细胞系。miR-34c的恢复显著降低了KITLG mRNA和蛋白的表达，而内源性miR-34c的沉默增加了KITLG蛋白的表达。mir -34c介导的KITLG下调与抑制CRC细胞的增殖、细胞转化、迁移和侵袭以及促进凋亡有关。通过其特异性siRNA敲低KITLG，证实了KITLG下调对CRC细胞中miR-34c的肿瘤抑制作用的关键作用。总之，我们的研究结果表明，miR-34c可能干扰kitlg相关的CRC，可能是CRC患者的一个新的分子靶点。
MiR-34c is considered a potent tumour suppressor because of its negative regulation of multiple target mRNAs that are critically associated with tumorigenesis and metastasis. In the present study, we demonstrated a novel target of miR-34c, KITLG, which has been implicated in colorectal cancer (CRC). First, we found a significant negative relationship between miR-34c and KITLG mRNA expression levels in CRC cell lines, including HT-29, HCT-116, SW480 and SW620 CRC cell lines. In silico analysis predicted putative binding sites for miR-34c in the 3 untranslated region (3UTR) of KITLG mRNA. A dual-luciferase reporter assay further confirmed that KITLG is a direct target of miR-34c. Then, the cell lines were infected with lentiviruses expressing miR-34c or a miR-34c specific inhibitor. Restoration of miR-34c dramatically reduced the expression of KITLG mRNA and protein, while silencing of endogenous miR-34c increased the expression of KITLG protein. The miR-34c-mediated down-regulation of KITLG was associated with the suppression on proliferation, cellular transformation, migration and invasion of CRC cells, as well as the promotion on apoptosis. Knockdown of KITLG by its specific siRNA confirmed a critical role of KITLG down-regulation for the tumour-suppressive effects of miR-34c in CRC cells. In conclusion, our results demonstrated that miR-34c might interfere with KITLG-related CRC and could be a novel molecular target for CRC patients.