DRAM1 regulates the migration and invasion of hepatoblastoma cells via autophagy-EMT pathway.
DRAM1 regulates the migration and invasion of hepatoblastoma cells via autophagy-EMT pathway.
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DOI：
10.3892/ol.2018.8937
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发表时间：
2018-08
期刊：
影响因子：
2.9
通讯作者：
Zhou GQ
中科院分区：
文献类型：
--
作者：
Chen C;Liang QY;Chen HK;Wu PF;Feng ZY;Ma XM;Wu HR;Zhou GQ
DNA损伤调节的自噬调节因子1（DRAM 1）是TP 53介导的自噬的靶点，并已被报道可促进胶质母细胞瘤干细胞的迁移和侵袭能力。然而，DRAM 1对癌细胞侵袭和迁移的确切贡献以及潜在机制仍不清楚。本研究采用小干扰RNA（siRNA）或短发夹RNA（短发夹RNA）介导的DRAM 1基因敲低技术，在体外和体内检测肝母细胞瘤细胞的迁移和侵袭能力。为探讨其机制，采用免疫印迹和免疫荧光法检测自噬相关蛋白和上皮间质转化（EMT）相关标志物的表达。结果表明，特异性siRNA敲低DRAM 1可消除细胞自噬，并抑制HepG 2细胞在Transwell试验中的迁移和侵袭，这可能被雷帕霉素处理逆转。此外，DRAM 1基因敲低可增加HepG 2细胞中E-Cadherin的表达，降低vimentin的表达，雷帕霉素处理可逆转该作用。这些结果表明，DRAM 1可能通过自噬-EMT途径参与调控HepG 2细胞的迁移和侵袭。
DNA-damage regulated autophagy modulator 1 (DRAM1) is known as a target of TP53-mediated autophagy, and has been reported to promote the migration and invasion abilities of glioblastoma stem cells. However, the precise contribution of DRAM1 to cancer cell invasion and migration, and the underlying mechanisms remain unclear. In the present study, small interfering (si)RNA or short hairpin RNA mediated knockdown of DRAM1 was performed in hepatoblastoma cells and the migration and invasion abilities were detected in vitro and in vivo. To investigate the underlying mechanisms, western blotting and immunofluorescence were used to detect the expression of autophagy-associated proteins and epithelial-mesenchymal-transition (EMT)-associated markers. The results showed that DRAM1 knockdown by specific siRNA abrogated cell autophagy, as well as inhibited the migration and invasion of HepG2 cells in Transwell assays, which may be reversed by rapamycin treatment. In addition, DRAM1 knockdown increased the expression of E-Cadherin while decreased the expression of vimentin in HepG2 cells, which was also be reversed by rapamycin treatment. Taken together, these results suggest that DRAM1 is involved in the regulation of the migration and invasion of HepG2 cells via autophagy-EMT pathway.
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