Sirtuins are NAD(+) -dependent deacetylases that regulate a range of cellular processes. Although diverse functions of sirtuins have been proposed, those functions of SIRT6 and SIRT7 that are mediated by their interacting proteins remain elusive. In the present study, we identified SIRT6- and SIRT7-interacting proteins, and compared their interactomes to investigate functional links. Our interactomes revealed 136 interacting proteins for SIRT6 and 233 for SIRT7 while confirming seven and 111 proteins identified previously for SIRT6 and SIRT7, respectively. Comparison of SIRT6 and SIRT7 interactomes under the same experimental conditions disclosed 111 shared proteins, implying related functional links. The interaction networks of interactomes indicated biological processes associated with DNA repair, chromatin assembly, and aging. Interactions of two highly acetylated proteins, nucleophosmin (NPM1) and nucleolin, with SIRT6 and SIRT7 were confirmed by co-immunoprecipitation. NPM1 was found to be deacetylated by both SIRT6 and SIRT7. In senescent cells, the acetylation level of NPM1 was increased in conjunction with decreased levels of SIRT6 and SIRT7, suggesting that the acetylation of NPM1 could be regulated by SIRT6 and SIRT7 in the aging process. Our comparative interactomic study of SIRT6 and SIRT7 implies important functional links to aging by their associations with interacting proteins. All MS data have been deposited in the ProteomeXchange with identifiers PXD000159 and PXD000850 (http://proteomecentral.proteomexchange.org/dataset/PXD000159, http://proteomecentral.proteomexchange.org/dataset/PXD000850).

These results suggest that SOX4 contributes to hepatocarcinogenesis by inhibiting p53-mediated apoptosis and that its overexpression might be a useful prognostic marker for survival after surgical resection.

TIS21 negatively regulated hepatocarcinogenesis in part by disruption of the FoxM1-cyclin B1 regulatory loop, thereby inhibiting proliferation of transformed cells developed in mouse and human livers.

Hepatocellular carcinoma is one of the most lethal cancers worldwide. More accurate stratification of patients at risk is necessary to improve its clinical management. As epithelial-mesenchymal transition is critical for the invasiveness and metastasis of human cancers, we investigated expression profiles of 12 genes related to epithelial-mesenchymal transition through a real-time polymerase chain reaction. From a univariate Cox analysis for a training cohort of 128 hepatocellular carcinoma patients, four candidate genes (E-cadherin [CDH1], inhibitor of DNA binding 2 [ID2], matrix metalloproteinase 9 [MMP9], and transcription factor 3 [TCF3]) with significant prognostic values were selected to develop a risk score of patient survival. Patients with high risk scores calculated from the four-gene signature showed significantly shorter overall survival times. Moreover, the multivariate Cox analysis revealed that fourgene signature (P = 0.0026) and tumor stage (P = 0.0023) were independent prognostic factors for overall survival. Subsequently, the four-gene signature was validated in an independent cohort of 231 patients from three institutions, in which high risk score was significantly correlated with shorter overall survival (P = 0.00011) and disease-free survival (P = 0.00038). When the risk score was entered in a multivariate Cox analysis with tumor stage only, both the risk score (P = 0.0046) and tumor stage (P = 2.6 · 10 -9) emerged as independent prognostic factors. In conclusion, we suggest that the proposed gene signature may improve the prediction accuracy for survival of hepatocellular carcinoma patients, and complement prognostic assessment based on important clinicopathologic parameters such as tumor stage. (Cancer Sci 2010; 101: 1521-1528 H epatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the most common primary hepatic malignancy, being responsible for 80% of malignant tumors in adult livers. Moreover, its mortality is third among all cancers, behind only lung and colon cancer.(1) HCC is known for its endemic prevalence in Asia and Africa, and the incidence of HCC has doubled in the USA and Europe in the past four decades.(1-3) HCC is resistant to conventional chemotherapy and is rarely amenable to radiotherapy, (4) leaving this disease with no effective therapeutic options and a very poor prognosis. Although the major etiological agents have been identified, the molecular pathogenesis of HCC remains unclear.(5) It is therefore important to identify molecular targets to develop novel diagnostic, therapeutic, and preventive strategies.Epithelial-mesenchymal transition (EMT) is a key step during embryogenesis but also plays a critical role in cancer progression, through which epithelial cancers invade and metastasize. (6) Therefore, EMT-related pathways have been studied in relation to cancer management and drug resistance, for instance in breast cancer (7) and ovarian cancer. (8) The existence of EMT in vivo has been controversial due to its spatial and temporal heterogeneit...

Background The aim of the present study was to compare the prognostic impact of anatomic resection (AR) versus non-anatomic resection (NAR) on patient survival after resection of a single hepatocellular carcinoma (HCC). Methods To control for confounding variable distributions, a 1-to-1 propensity score match was applied to compare the outcomes of AR and NAR. Among 710 patients with a primary, solitary HCC of <5.0 cm in diameter that was resectable by either AR or NAR from 2003 to 2007 in Japan and Korea, 355 patients underwent NAR and 355 underwent AR of at least one section with complete removal of the portal territory containing the tumor. Results Overall survival (OS) was better in the AR than NAR group (hazard ratio 1.67, 95% confidence interval 1.28-2.19, P < 0.001) while disease-free survival showed no significant difference. Significantly fewer patients in the AR than NAR group developed intrahepatic HCC recurrence and multiple intrahepatic recurrences. Patients with poorly differentiated HCC who underwent AR had improved disease-free survival and OS. Conclusions Anatomic resection decreases the risk of tumor recurrence and improves OS in patients with a primary, solitary HCC of <5.0 cm in diameter.