Obstetrics and Gynecology Hospital, Fudan University, Shanghai, China.
Department of Obstetrics and Gynecology of Shanghai Medical School, Fudan University, Shanghai, China.
Acta Biochim Biophys Sin (Shanghai). 2019 May 23;51(5):455-462. doi: 10.1093/abbs/gmz027.
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 β-catenin resulted in reduced expression of LIN28B and increased expression of Let-7a. Knockdown of β-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 β-catenin/LIN28B/Let-7a pathway may be crucial for the regulation of cell proliferation in human choriocarcinoma cells.
绒癌是一种罕见的恶性滋养细胞肿瘤。然而，绒癌的调控机制尚不清楚。本研究首先阐明 LIN28B 在人绒癌组织和绒癌细胞系中高表达。我们的数据进一步表明，小干扰 RNA 敲低 LIN28B 导致 JAR 细胞中 Let-7a 的表达增加。此外，沉默 LIN28B 抑制 IGF2BP1 表达并抑制细胞增殖能力，这两者均可被 Let-7a 抑制剂显著恢复。相反，LIN28B 的过表达改善了细胞增殖，可被 Let-7a 模拟物抑制。β-catenin 的敲低导致 LIN28B 的表达减少和 Let-7a 的表达增加。β-catenin 的敲低也导致细胞增殖减少，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，β-catenin/LIN28B/Let-7a 通路可能是调节人绒癌细胞增殖的关键。
