Journal
MOLECULAR MEDICINE REPORTS
Volume 20, Issue 4, Pages 3003-3010Publisher
SPANDIDOS PUBL LTD
DOI: 10.3892/mmr.2019.10577
Keywords
sterol regulatory element-binding protein 2; esophageal squamous cell carcinoma; c-Myc; statin
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Funding
- National Science Foundation of China [81401933]
- Shanghai Science and Technology Committee [13ZR1461300]
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Dysregulations of the mevalonate pathway (MVA) have been previously identified. Our previous study demonstrated that 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), the rate-limiting enzyme of the MVA pathway, was upregulated in esophageal squamous cell carcinoma (ESCC) and statin-inhibited ESCC tumorigenesis. However, the underlying mechanism of HMGCR regulation in ESCC remains unknown. In the present study, western blotting and immunohistochemistry analysis demonstrated that sterol regulatory element-binding protein 2 (SREBP2), the master regulator for HMGCR, was upregulated in ESCC clinical samples. Overexpression of SREBP2 expression in ESCC cell lines promoted the growth, migration and colony formation of cancer cells in the MTT, Boyden chamber and soft agar assays, respectively, which was inhibited by lovastatin. Downregulation of SREBP2 expression in ESCC cell lines inhibited the viability, and migration and colony formation abilities of cancer cells. Assessment of the molecular mechanism demonstrated that SREBP2 interacted with c-Myc and cooperated with c-Myc to activate HMGCR expression. Collectively, the present study identified SREBP2 as an oncogene associated with the tumorigenesis of ESCC and further demonstrated the therapeutic effects of statins in ESCC.
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