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固醇调节元件结合蛋白1与c-Myc协同促进结直肠癌中的上皮-间质转化。

Sterol regulatory element-binding protein 1 cooperates with c-Myc to promote epithelial-mesenchymal transition in colorectal cancer.

作者信息

Zhai Duanyang, Cui Chunhui, Xie Lang, Cai Lianxu, Yu Jinlong

机构信息

Department of General Surgery, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510530, P.R. China.

出版信息

Oncol Lett. 2018 Apr;15(4):5959-5965. doi: 10.3892/ol.2018.8058. Epub 2018 Feb 15.

Abstract

Metastasis is the primary cause of mortality in colorectal cancer (CRC), the mechanism of which remains unclear. In the present study, by detecting mRNA expression using a reverse transcription-quantitative polymerase chain reaction (qPCR), it was revealed that sterol regulatory element-binding protein 1 (SREBP1) is highly expressed in CRC. Using a cell wound healing assay and a cell invasion assay, a novel metastasis-promoting role for SREBP1 in CRC was identified. Furthermore, snail family transcriptional repressor 1 (SNAIL) was identified as a key downstream effector of SREBP1 in CRC by the use of small interfering RNA against SNAIL. Additionally, using co-immunoprecipitation and chromatin immunoprecipitation-qPCR assays, it was demonstrated that SREBP1 interacts with c-MYC to enhance the binding of c-MYC to the promoter of the mesenchymal gene, SNAIL, thereby increasing SNAIL expression and accelerating epithelial-mesenchymal transition. These results indicated a novel role for SREBP1 and provide insight into the regulatory mechanisms of the c-Myc oncogene in CRC, which may function as a potential therapeutic target for CRC treatment.

摘要

转移是结直肠癌(CRC)患者死亡的主要原因,其机制尚不清楚。在本研究中,通过逆转录定量聚合酶链反应(qPCR)检测mRNA表达,发现固醇调节元件结合蛋白1(SREBP1)在CRC中高表达。使用细胞划痕愈合试验和细胞侵袭试验,确定了SREBP1在CRC中具有促进转移的新作用。此外,通过使用针对蜗牛家族转录抑制因子1(SNAIL)的小干扰RNA,确定SNAIL是SREBP1在CRC中的关键下游效应因子。此外,通过免疫共沉淀和染色质免疫沉淀-qPCR试验,证明SREBP1与c-MYC相互作用,增强c-MYC与间充质基因SNAIL启动子的结合,从而增加SNAIL表达并加速上皮-间质转化。这些结果表明了SREBP1的新作用,并为c-Myc癌基因在CRC中的调控机制提供了见解,其可能作为CRC治疗的潜在靶点发挥作用。

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