Affiliation:
1. School of Pharmacy Binzhou Medical University Yantai China
2. Shandong Technology Innovation Center of Molecular Targeting and Intelligent Diagnosis, and Treatment Binzhou Medical University Yantai China
3. The First School of Clinical Medicine Binzhou Medical University Yantai China
4. Department of Urology The Affiliated Yantai Yuhuangding Hospital of Qingdao University Yantai China
Abstract
AbstractAmplification of amino acids synthesis is reported to promote tumorigenesis. The serine/glycine biosynthesis pathway is a reversible conversion of serine and glycine catalyzed by cytoplasmic serine hydroxymethyltransferase (SHMT)1 and mitochondrial SHMT2; however, the role of SHTM1 in renal cell carcinoma (RCC) is still unclear. We found that low SHMT1 expression is correlated with poor survival of RCC patients. The in vitro study showed that overexpression of SHMT1 suppressed RCC proliferation and migration. In the mouse tumor model, SHMT1 significantly retarded RCC tumor growth. Furthermore, by gene network analysis, we found several SHMT1‐related genes, among which homeobox D8 (HOXD8) was identified as the SHMT1 regulator. Knockdown of HOXD8 decreased SHMT1 expression, resulting in faster RCC growth, and rescued the SHMT1 overexpression‐induced cell migration defects. Additionally, ChIP assay found the binding site of HOXD8 to SHMT1 promoter was at the −456~−254 bp region. Taken together, SHMT1 functions as a tumor suppressor in RCC. The transcription factor HOXD8 can promote SHMT1 expression and suppress RCC cell proliferation and migration, which provides new mechanisms of SHMT1 in RCC tumor growth and might be used as a potential therapeutic target candidate for clinical treatment.
Funder
National Natural Science Foundation of China
Subject
Cancer Research,Oncology,General Medicine
Cited by
1 articles.
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