ABSTRACT
Sorting nexin 16(SNX16),a member of the SNX family,contains a phoxhomology domain that is prone to bind with phosphatidylinositol-3-phosphate domain and a C-terminal coiled-coil domain. SNX16 participates in diverse cellular processes such as endocytosis,protein sorting,and signal transduction. The dysfunctions of SNX16 are demonstrated to be involved in the occurrence of several diseases.Here,we review the structural characteristics and biological functions of SNX16 and discuss the regulatory role of SNX16 in diseases,surveying how SNX16 can be applied to the prevention and treatment of related disorders.
Subject(s)
Endosomes , Sorting Nexins , Sorting Nexins/chemistry , Sorting Nexins/metabolism , Endosomes/metabolism , Protein Transport , Signal TransductionABSTRACT
Osteosarcoma is the most common type of bone cancer. In the present study, by way of PCR-based microarrays, we found that TUT1, a nucleotidyl transferase, was significantly downregulated in osteosarcoma, compared with adjacent normal tissues. In the current study, we performed PCR-based microarrays using the cDNA prepared from osteosarcoma and adjacent normal tissues. The enforced expression of TUT1 was able to inhibit cell proliferation in U2OS and MG63 cells, while its knockdown using small interfering RNA (siRNA) oligos promoted cell proliferation. At the molecular level, we found that TUT1 could inhibit the expression levels of PPARgamma and SREBP-1c, two key regulators in lipogenesis, through upregulation of microRNA-24 and microRNA-29a. Therefore, our results suggest that TUT1 may act as a tumor suppressor for osteosarcoma, which might provide a novel mechanism for the tumor development.
Subject(s)
Gene Expression Regulation, Neoplastic , Lipogenesis/genetics , MicroRNAs/genetics , Nucleotidyltransferases/genetics , Osteosarcoma/genetics , Osteosarcoma/metabolism , Base Sequence , Cell Cycle/genetics , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation , Gene Knockdown Techniques , Humans , MicroRNAs/chemistry , Nucleotidyltransferases/metabolism , Osteosarcoma/pathology , RNA Interference , RNA, Messenger/chemistry , RNA, Messenger/geneticsABSTRACT
Many studies have reported the association between the FASLG -844T/C polymorphism and cancer risk, but the data are remaining controversial. A pooled analysis was performed to assess this relationship comprehensively. Medline, PubMed, Embase and Web of Science were searched, and data were extracted and cross-checked independently by three authors. A total of 18 published studies including 22389 subjects were involved in this analysis. Overall, the -844C allele was associated with a significantly increased cancer risk (for CC versus TT: OR=1.23, 95% confidence interval (CI)=1.04-1.45; for CC+TC versus TT: OR=1.15, 95% CI=1.01-1.30; for CC versus TT+TC: OR=1.20, 95% CI=1.05-1.38). In the subgroup analysis by ethnicity, significantly elevated risks were found among Asians (for CC versus TT: OR=1.61, 95% CI=1.37-1.89; for CC+TC versus TT: OR=1.36, 95% CI=1.16-1.60; for CC versus TT+TC: OR=1.44, 95% CI=1.22-1.70). In the subgroup analysis by study design, significantly increased risks were found among population-based case-control studies (for CC versus TT: OR=1.40, 95% CI=1.06-1.84; for CC+TC versus TT: OR=1.25, 95% CI=1.01-1.55; for CC versus TT+TC: OR=1.31, 95% CI=1.06-1.61). These findings indicate that the FASLG -844C allele is emerging as a low-penetrant cancer susceptibility allele for cancer development. However, more comprehensive understanding of the association would certainly have an immense prospect in the promising field of individualised preventive care.
