Zhai Duanyang, Cui Chunhui, Xie Lang, Cai Lianxu, Yu Jinlong
Department of General Surgery, Zhujiang Hospital of Southern Medical University, Guangzhou, Guangdong 510530, P.R. China.
Oncol Lett. 2018 Apr;15(4):5959-5965. doi: 10.3892/ol.2018.8058. Epub 2018 Feb 15.
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.
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。