Human HLA-F adjacent transcript 10 (FAT10) is the only ubiquitin-like protein that can directly target substrates for degradation by proteasomes, but it can also stabilize the expression of certain substrates by antagonizing ubiquitination, through mechanisms as yet uncharacterized. In this study, we show how FAT10 stabilizes the translation elongation factor eEF1A1, which contributes to cancer cell proliferation. FAT10 overexpression increased expression of eEF1A1, which was sufficient to promote proliferation of cancer cells.Mechanistic investigations revealed that FAT10 competed with ubiquitin (Ub) for binding to the same lysines on eEF1A1 to form either FAT10-eEF1A1 or Ub-eEF1A1 complexes, respectively, such that FAT10 overexpression decreased Ub-eEF1A1 levels and increased FAT10-eEF1A1 levels. Overall, our work establishes a novel mechanism through which FAT10 stabilizes its substrates, advancing understanding of the biological function of FAT10 and its role in cancer. Cancer Res; 76(16); 4897-907.Ó2016 AACR.
Many studies have evaluated the relationships between alkaline phosphatase (ALP) levels and the prognosis for osteosarcoma. However, a consensus has yet to be reached. We completed a meta-analysis to assess the significance of ALP and prognosis for osteosarcoma. We retrieved eligible documents from the PubMed and Embase databases and extracted related data from those documents. The overall survival (OS), hazard ratio (HR) and event-free survival (EFS) HR were obtained after combination to evaluate the impacts of ALP levels on prognosis for osteosarcoma. After screening, a total of 12 documents published between 1999 and 2013 were included. The ALP levels on OS were evaluated in nine documents. The pooled HRs was 1.78 (95% CI: 1.52-2.07, p < .05). The ALP levels on EFS were determined in eight documents. The pooled HRs was 1.58 (95% CI: 1.37-1.82, p < .05). Begg's test (OS, p > .754; EFS, p > .386) and Egger's test (OS, p > .649; EFS, p > .274) showed that there was no significant publication bias during analytic process. In summary, our meta-analysis shows that a higher level of ALP can decrease the OS and EFS in patients with osteosarcoma and ALP is an important biological indicator for patients with osteosarcoma.
Autophagy-related gene 7 (ATG7) and miR-106a play an important role in cancer cell autophagy and apoptosis, but the outcome of ATG7 and miR-106a in colorectal cancer (CRC) still remains not clear. In this study, we found that ATG7 and miR-106a expression were mutually related with cell death and prognosis in CRC patients. In addition, we also showed that ATG7 and miR-106a expression were changeable in colorectal cancer cell lines when compared with normal cell lines, but ATG7 and miR-106a mRNA level was negatively correlated. Furthermore, ATG7 protein and mRNA levels decreased after over-expression of miR-106a, whereas the suppression of ATG7 had the opposite effect. We confirmed that miR-106a down-regulated ATG7 mRNA level by binding the specific sequence of ATG7 mRNA 3'UTR region. Moreover, the over-expression of ATG7 induced CRC cells death both in vitro and in vivo. Taken together, our study data demonstrated that ATG7 aggravated the cell death of CRC, which was inhibited by miR-106a.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.