The stromal cell derived factor-1 (SDF-1) rs1801157 gene polymorphism has been implicated in susceptibility to cancer, but the results were inconclusive. The current study was to precisely investigate the association between SDF-1 rs1801157 polymorphism and cancer risk using meta-analysis and the false positive report probability (FPRP) test. All 17,876 participants were included in the study. The meta-analysis results indicated a significant association between the SDF-1 rs1801157 polymorphism and cancer risk. By subgroup analyses, the results detected that the SDF-1 rs1801157 polymorphism was associated with cancer susceptibility among Asians and Caucasians. Additionally, we also found significant associations between the SDF-1 rs1801157 polymorphism and susceptibility to different types of cancer. However, to avoid a “false positive report”, we further investigated the significant associations observed in the present meta-analysis using the FPRP test. Interestingly, the results of the FPRP test indicated that only 4 gene models were truly associated with cancer risk, especially in Asians. Moreover, we confirmed that the SDF-1 rs1801157 gene polymorphism was only associated with lung and urologic cancer risk. In summary, this study suggested that the SDF-1 rs1801157 polymorphism may serve as a risk factor for cancer development among Asians, especially an increased risk of urologic and lung cancers.

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Background Galangin (GLN), a pure natural flavonoid compound found in plants, has been shown to exert anti-cancer effects against multiple cancer types, including glioma. However, its underlying molecular mechanism remains unclear. Epithelial-to-mesenchymal transition (EMT) performs an important function in the genesis and development of cancer. Skp2, a pivotal component of SCF Skp2 E3 ubiquitin ligase, has been shown to function as an oncogene in GBM invasion that contributes to the EMT process. Thus, we explored whether GLN inhibited Skp2-mediated EMT and the mechanism underlying the Skp2 degradation pathway. Methods CCK-8 assay, wound healing assay and transwell assay were used to examine cell proliferation, migration, and invasion after treatment with or without GLN. RT-PCR and Western blotting analysis were performed to evaluate mRNA and protein expression, respectively. Co-immunoprecipitation was conducted to detect ubiquitinated Skp2 levels in vitro and in vivo after GLN treatment. Bioluminescence imaging was performed to examine the intracranial tumor size of U87 xenograft mice. Microscale thermophoresis (MST) experiment was used to detect interactions between Skp2 and GLN. Results GLN suppressed GBM cell growth, migration, and invasion, and also downregulated the expression of Skp2 and mesenchymal markers (Zeb1, N-cadherin, snail, vimentin) in vitro. Moreover, the overexpression of Skp2 in GBM cells decreased the effect of GLN on EMT. Furthermore, we demonstrated that GLN degraded skp2 protein through the ubiquitination proteasome pathway and directly interacted with skp2 protein, as shown through the MST assay. Conclusion This study is the first to identify Skp2 as a novel target of GLN for the treatment of GBM and report of Skp2 protein degradation in a ubiquitination proteasome pathway. Results from our study indicated the potential of GLN for the treatment of GBM through ubiquitin-mediated degradation of Skp2.

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