Suppression of SIK1 by miR-141 in human ovarian cancer cell lines and tissues
Suppression of SIK1 by miR-141 in human ovarian cancer cell lines and tissues
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DOI：
10.3892/ijmm.2016.2553
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发表时间：
2016-06-01
影响因子：
5.4
通讯作者：
Liu, Nai-Fu
中科院分区：
文献类型：
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作者：
Chen, Jin-Long;Chen, Fang;Liu, Nai-Fu
上皮性卵巢癌（EOC）是全球第六大女性常见癌症，也是发达国家最常见的致命妇科恶性肿瘤。造成这种情况的一个主要原因是，人们对导致这种高度侵袭性疾病的分子事件知之甚少。在本研究中，我们证明了盐诱导激酶1 （SIK1，也被称为MSK/SIK/ snfl1lk）在卵巢癌组织样本中下调。使用HEY卵巢癌细胞，我们注意到SIK1过表达抑制增殖以及癌症干细胞相关性状。沉默SIK1可促进EG卵巢癌细胞系的增殖。我们使用三种常用的预测算法：miRanda、TargetScan和PicTar对潜在的microrna （miRNAs或miRs）靶位点进行了分析。三种算法均预测miR-141靶向SIK1的3UTR。随后的实验不仅证实了这一预测，还表明miR-141与该疾病的进展有关。最后，我们发现miR-141促进EG细胞的增殖，而沉默miR-141恢复SIK1表达并抑制HEY细胞的增殖。阐明卵巢癌的分子机制不仅使我们进一步了解疾病的发病机制和进展，而且为有效的治疗提供了新的靶点。
Epithelial ovarian cancer (EOC), the sixth most common cancer in women worldwide, is the most commonly fatal gynecologic malignancy in developed countries. One of the main reasons for this is that relatively little was known about the molecular events responsible for the development of this highly aggressive disease. In the present study, we demonstrated that salt-inducible kinase 1 (SIK1; which is also known as MSK/SIK/SNF1LK) was downregulated in ovarian cancer tissue samples. Using HEY ovarian cancer cells, we noted that SIK1 overexpression inhibited proliferation as well as cancer stem cell-associated traits. Silencing SIK1 promoted the proliferation of the EG ovarian cancer cell line. We performed an analysis of potential microRNAs (miRNAs or miRs) target sites using three commonly used prediction algorithms: miRanda, TargetScan and PicTar. All three algorithms predicted that miR-141 targets the 3UTR of SIK1. Subsequent experiments not only confirmed this prediction, but also showed that miR-141 was associated with the progression of this disease. Finally, we found that miR-141 promoted proliferation of EG cells, whereas silencing miR-141 restored SIK1 expression and inhibited the proliferation of the HEY cells. Elucidating the molecular mechanism of ovarian cancer not only enables us to further understand the pathogenesis and progression of the disease, but also provides new targets for effective therapies.