LncRNA-HOST2 regulates cell biological behaviors in epithelial ovarian cancer through a mechanism involving microRNA let-7b
LncRNA-HOST2 regulates cell biological behaviors in epithelial ovarian cancer through a mechanism involving microRNA let-7b
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LncRNA-HOST2通过涉及microRNA let-7b的机制调节上皮性卵巢癌的细胞生物学行为
DOI：
10.1093/hmg/ddu502
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发表时间：
2015-02-01
影响因子：
3.5
通讯作者：
Hui, Ning
中科院分区：
文献类型：
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作者：
Gao, Yuan;Meng, Hao;Hui, Ning
最近，在哺乳动物基因组中发现了大量的长非编码RNA(IncRNAs)，它们在进化上是保守的，可能在许多生物学事件中发挥作用，特别是在人类多种癌症的发病机制中。一个IncRNA，命名为HOST2(人卵巢癌特异性转录本2)，曾被报道在人卵巢癌中高水平表达。然而，HOST2如何在卵巢癌发生中调节基因功能仍然是个谜。在这里，我们首次报道，HOST2通过在生物学行为的关键方面发挥作用，促进上皮性卵巢癌中肿瘤细胞的迁移、侵袭和增殖。在本研究中，生物信息学分析表明，HOST2与有效的肿瘤抑制因子microRNA let-7b结合，并被证实是针对HOST2的。我们的结果表明，HOST2含有一个let-7b结合位点，并通过作为分子海绵来调节let-7b的可用性。HOST2抑制let-7b的功能，后者在转录后抑制靶基因的表达，包括一些调节细胞生长和运动的癌基因。此外，了解HOST2/let-7b依赖的调控可能会导致诊断和治疗这种致命疾病的替代方法。
Recently, a large number of long non-coding RNAs (IncRNAs) have been reported in mammalian genomes and are evolutionarily conserved and presumably function in many biological events, especially in the pathogenesis of diverse human cancers. A IncRNA, named HOST2 (human ovarian cancer-specific transcript 2), was once reported to specifically be expressed at high level in human ovarian cancer. However, how HOST2 acts to regulate gene functions in ovarian carcinogenesis has remained enigmatic. Here we report, for the first time, that HOST2 promotes tumor cell migration, invasion and proliferation in epithelial ovarian cancer by working in key aspects of biological behaviors. In the present study, bioinformatics analysis indicated that HOST2 binds with microRNA let-7b, a potent tumor suppressor, which was then verified to target HOST2. Our results showed that HOST2 harbors a let-7b binding site and modulates let-7b availability by acting as a molecular sponge. HOST2 inhibits let-7b functions, which post-transcriptionally suppress the expression of targets, including some oncogenes that regulate cell growth and motility. Additionally, understanding HOST2/let-7b-dependent regulation may lead to alternative approaches for the diagnosis and cure of this deadly disease.