CircECE1 activates energy metabolism in osteosarcoma by stabilizing c-Myc.
CircECE1 activates energy metabolism in osteosarcoma by stabilizing c-Myc.
复制标题
DOI：
10.1186/s12943-020-01269-4
复制
发表时间：
2020-10-26
期刊：
影响因子：
37.3
通讯作者：
Ma J
中科院分区：
文献类型：
--
作者：
Shen S;Yao T;Xu Y;Zhang D;Fan S;Ma J
骨肉瘤（OS）是最常见的恶性骨肿瘤，预后较差。环状 RNA (circRNA) 在 OS 进展中的潜在参与尚未被探索。在这里，我们报道了 CircECE1，一种源自人类 ECE1 的环状 RNA，在 OS 的能量代谢中发挥着关键作用。进行RIP芯片序列分析来确认CircECE1，通过CircECE1的过表达或敲低来验证其在143B和U2OS中的功能。 RNA免疫沉淀和免疫沉淀用于验证CircECE1对蛋白c-Myc的调节作用，免疫共沉淀用于验证CircECE1与SPOP之间的竞争结合关系。通过海马实验、蛋白质印迹和免疫组化评估CircECE1对能量代谢的影响。我们发现 CircECE1 在 OS 组织和细胞中高表达，并且 CircECE1 敲低可抑制体外和体内的肿瘤增殖和转移。此外，CircECE1 在体外和体内显着促进 OS 细胞的葡萄糖代谢。从机制上讲，CircECE1 与 c-Myc 相互作用，防止斑点型 POZ 介导的 c-Myc 泛素化和降解。 C-Myc 抑制硫氧还蛋白结合蛋白 (TXNIP) 转录，随后激活 Warburg 效应。 CircECE1 通过 c-Myc/TXNIP 轴调节 Warburg 效应。 CircECE1介导的信号转导在操作系统过程和能量代谢中发挥着重要作用。这些发现可能会确定 OS 分子治疗的新靶点。在线版本包含可在 10.1186/s12943-020-01269-4 获取的补充材料。
Osteosarcoma (OS) is the most common malignant bone tumor and has a poor prognosis. The potential involvement of circular RNAs (circRNAs) in OS progression remains unexplored. Here, we report that CircECE1, a circular RNA derived from human ECE1, plays a critical role in energy metabolism in OS. The RIP chip sequence assay was performed to confirm CircECE1, through overexpression or knockdown of CircECE1 to verify its function in 143B and U2OS. RNA immunoprecipitation and immunoprecipitation were used to verify CircECE1’s regulation of protein c-Myc and co- immunoprecipitation was used to verified the competitive binding relationship between CircECE1 and SPOP. The influence of CircECE1 on energy metabolism was evaluated by seahorse experiment, western blot, and immunohistochemistry. We found that CircECE1 is highly expressed in OS tissues and cells and that CircECE1 knockdown suppresses tumor proliferation and metastasis both in vitro and in vivo. Further, CircECE1 significantly promotes glucose metabolism in OS cells in vitro and in vivo. Mechanistically, CircECE1 interacts with c-Myc to prevent speckle-type POZ-mediated c-Myc ubiquitination and degradation. C-Myc inhibits thioredoxin binding protein (TXNIP) transcription and subsequently activates the Warburg effect. CircECE1 regulates the Warburg effect through the c-Myc/TXNIP axis. CircECE1 mediated signal transduction plays a important role in OS process and energy metabolism. These findings may identify novel targets for OS molecular therapy. The online version contains supplementary material available at 10.1186/s12943-020-01269-4.
登录
查看更多内容
影响因子：
44.1
作者：
通讯作者：
--
影响因子：
37.3
作者：
Morrison JA;Pike LA;Sams SB;Sharma V;Zhou Q;Severson JJ;Tan AC;Wood WM;Haugen BR
通讯作者：
Haugen BR
影响因子：
29
作者：
Sanderson SM;Locasale JW
通讯作者：
Locasale JW
影响因子：
64.5
作者：
Hsu, Peggy P.;Sabatini, David M.
通讯作者：
Sabatini, David M.
DOI：
10.1073/pnas.1501555112
发表时间：
2015-04-28
影响因子：
11.1
作者：
Shen, Liangliang;O'Shea, John M.;Ayer, Donald E.
通讯作者：
Ayer, Donald E.