β -catenin/LIN28B promotes the proliferation of human choriocarcinoma cells via Let-7a repression
β -catenin/LIN28B promotes the proliferation of human choriocarcinoma cells via Let-7a repression
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β-catenin/LIN28B 通过 Let-7a 抑制促进人绒毛膜癌细胞增殖
DOI：
10.1093/abbs/gmz027
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发表时间：
2019-05-01
影响因子：
3.7
通讯作者：
Zhao, Hongbo
中科院分区：
文献类型：
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作者：
Wu, Jing;Feng, Xuan;Zhao, Hongbo
绒毛膜癌是一种罕见的恶性滋养细胞肿瘤。然而，绒毛膜癌调控的分子机制尚不清楚。在本研究中，我们首次阐明了LIN28B在人绒毛膜癌组织和绒毛膜癌细胞系中高表达。我们的数据进一步证明，通过小干扰RNA敲低LIN28B导致JAR细胞中Let-7a表达增加。此外，沉默LIN28B可抑制IGF2BP1的表达，抑制细胞增殖能力，而Let-7a抑制剂可显著恢复这两种功能。相比之下，Let-7a模拟物抑制了LIN28B过表达促进的细胞增殖。敲低-catenin导致LIN28B表达减少，Let-7a表达增加。-catenin的敲低也会导致细胞增殖的减少，这可以通过重新表达LIN28B或Let-7a抑制剂来恢复。总之，我们的数据表明-catenin/LIN28B/Let-7a通路可能对人绒毛膜癌细胞的细胞增殖调控至关重要。
Choriocarcinoma is a rare and malignant trophoblastic tumor. However, the molecular mechanisms by which choriocarcinoma is regulated remain unknown. In the present study, we first elucidated that LIN28B was highly expressed in human choriocarcinoma tissues and choriocarcinoma cell lines. Our data further demonstrated that knockdown of LIN28B by small interfering RNA caused an increase in Let-7a expression in JAR cells. In addition, silencing of LIN28B inhibited IGF2BP1 expression and suppressed cell proliferation capacity, both of which can be markedly restored by Let-7a inhibitor. In contrast, LIN28B over-expression-improved cell proliferation was inhibited by Let-7a mimic. Knockdown of -catenin resulted in reduced expression of LIN28B and increased expression of Let-7a. Knockdown of -catenin also caused a decrease in cell proliferation, which can be recovered by re-expression of LIN28B or by Let-7a inhibitor. Collectively, our data indicate that -catenin/LIN28B/Let-7a pathway may be crucial for the regulation of cell proliferation in human choriocarcinoma cells.