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

机译:甾醇调节元件结合蛋白1与c-Myc协同作用促进结直肠癌的上皮-间质转化

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摘要

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.
机译:转移是大肠癌(CRC)死亡的主要原因,其机制仍不清楚。在本研究中,通过使用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。使用细胞伤口愈合测定法和细胞侵袭测定法,鉴定了SREBP1在CRC中的新型转移促进作用。此外,通过使用针对SNAIL的小干扰RNA,将蜗牛家族转录阻遏物1(SNAIL)鉴定为CRC中SREBP1的关键下游效应子。此外,使用免疫共沉淀和染色质免疫沉淀-qPCR测定法,证明SREBP1与c-MYC相互作用以增强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-间质过渡。这些结果表明SREBP1的新作用,并提供了c-Myc癌基因在CRC中的调控机制的见解,其可能作为CRC治疗的潜在治疗靶标。

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