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Sirtuin 6 (SIRT6), a DNA repair-related gene, has undergone an extremely thorough study for its involvement in the development of many different cancers. The objective of our study was to explore the function and mechanism of SIRT6-induced regulation of prostate cancer (PCa). RT-PCR was performed to validate the levels of SIRT6 in PCa cell lines. Cell proliferation, migration, and invasion of cells with SIRT6 knockdown were assessed using CCK-8 assay, colony formation assay, wound-healing assay, and transwell assay. Western blot was applied to assess the related proteins. We found that SIRT6 expression was distinctly upregulated in PCa specimens and cells. Loss-of-functional assays revealed that SIRT6 silence suppressed the proliferation and metastasis of PCa cells. Mechanistic studies revealed that SIRT6 silence inhibited Wnt/β‐catenin signaling and EMT progress. Overall, the study confirmed the upregulation of SIRT6 in patients with PCa and its association with the progression. SIRT6 promoted PCa progression by regulating Wnt/β‐catenin signaling, providing a promising biomarker and treatment approach for preventing PCa.

Background Human hepatocellular carcinoma (HCC) lacks effective curative therapy and there is an urgent need to develop a novel molecular-targeted therapy for HCC. Selective tyrosine kinase inhibitors have shown promise in treating cancers including HCC. Tyrosine kinases c-Met and Trks are potential therapeutic targets of HCC and strategies to interrupt c-Met and Trks cross-signaling may result in increased effects on HCC inhibition. Methods The effects of Indo5 on c-Met and Trks activity were determined with in vitro kinase activity assay, cell-based signaling pathway activation, and kinases-driven cell transformation. The in vivo anti-tumor activity was determined with xenograft mice and liver orthotopic mice models. The co-expression of c-Met and TrkB in 180 pairs of HCC and adjacent normal tissues were detected using immunohistochemical staining. Results Indo5, a novel lead compound displayed biochemical potency against both c-Met and Trks with selectivity over 13 human kinases. Indo5 abrogated HGF-induced c-Met signaling activation and BDNF/NGF-induced Trks signal activation, c-Met or TrkB-mediated cell transformation and migration. Furthermore, Indo5 significantly decreased the growth of HCC cells in xenograft mice and improved the survival of mice with liver orthotopic tumors. In addition, co-expression of c-Met and TrkB in HCC patients was a predictor of poor prognosis, and combined inhibition of c-Met and TrkB exerted a synergistic suppressive effect on HCC. Conclusions These findings indicate that Indo5 is associated with marked suppression of c-Met and Trks co-expressing HCC, supporting its clinical development as an antitumor treatment for HCC patients with co-active c-Met and Trks signaling. Electronic supplementary material The online version of this article (10.1186/s13046-019-1104-4) contains supplementary material, which is available to authorized users.

Objective To investigate the association of circulating HER-2 level with metabolic syndrome in middle-aged and elderly population.Methods We conducted a population-based cross-sectional study with 687 participants aged 40 years or older from a community in Chongming District,Shanghai,China.Serum HER-2 levels were measured using ELISA.Metabolic syndrome was defined according to the updated National Cholesterol Education Program Adult Treatment Panel Ⅲ(NCEP ATP Ⅲ) criteria for AsianAmericans.Results After adjusting for other influencing factors,we found that the participants with metabolic syndrome(n = 370)had significantly higher HER-2 level compared with the control group(n = 317)([12.4 ± 2.3] ng / m L vs [8.2 ± 1.6] ng / m L,P 0.001).The serum HER-2 level increased(P 0.001) with the accumulation of the metabolic syndrome components.After adjusting for potential risk factors,multiple logistic regression analysis showed that the highest quartile of serum HER-2 was associated with increased risk of metabolic syndrome,with a fully adjusted odds ratio(OR) of 1.35(95% confidence interval [CI]: 1.14-2.31),P 0.001).Conclusion Serum HER-2 is independently associated with metabolic syndrome in middle-aged and elderly Chinese in this study.