Purpose The tripartite motif-containing family member TRIM37 is involved in a number of important biological and pathological processes, and it has recently been shown to be an essential regulator of protein ubiquitination and a contributor to tumorigenesis. We previously showed that TRIM37 is overexpressed in and promotes the proliferation and invasion of pancreatic cancer (PC). Methods Sphere formation, flow cytometric, qRT-PCR, western blot, colony formation, EdU incorporation, mouse xenograft model, TUNEL and IHC assays were performed to detect the role of TRIM37 in stemness and chemoresistance of PC in vitro and in vivo. Bioinformatics analysis and dual-luciferase reporter assays were used to determine which intracellular pathways might mediate the effects of TRIM37 in PC cells. Immunofluorescent(IF) staining, co-immunoprecipitation(CO-IP), protein stability and ubiquitination assays were performed to investigate the relationship between TRIM37 and PTEN. Results TRIM37 modulates the ubiquitination and degradation of the tumor suppressor phosphatase and tensin homolog (PTEN), which negatively regulates the AKT–GSK-3β–β-catenin signaling pathway, thereby sustaining aberrant activation of PC cells. High expression of TRIM37 combined with low expression of PTEN correlates with poor survival of PC patients. Conclusions Collectively, our results suggest that inhibition of the TRIM37–AKT–GSK-3β–β-catenin axis may be a promising strategy for treatment of PC.

Sirt1 is closely related to cells aging, and Sirt1 also plays an important role in diffuse large B-cell lymphoma (DLBCL). However, its mechanism remains unclear. Therefore, we investigated the mechanism of Sirt1 mediated drug-resistance in DLBCL, while the recombinant lentivirus was used to regulate Sirt1 gene expression in DLBCL cell lines. Subsequently, the effect of Sirt1 on DLBCL resistance to Adriamycin was analyzed in vitro. The results show that Sirt1 overexpression confers Adriamycin resistance in DLBCL cell lines. However, inhibition of Sirt1 sensitized DLBCL cell lines to Adriamycin cytotoxicity. Additionally, tumor-bearing mice were used to verify that Sirt1 overexpression confers Adriamycin resistance in vivo after chemotherapy. In addition, we used second-generation sequencing technology and bioinformatics analysis to find that Sirt1 mediated drug-resistance is related to the Peroxisome proliferator-activated receptor (PPAR) signaling pathway, especially to PGC-1α. Interestingly, the mitochondrial energy inhibitor, tigecycline, combined with Adriamycin reversed the cellular resistance caused by Sirt1 overexpression in vivo. Moreover, western blotting and CO-IP assay reconfirmed that Sirt1-mediated drug-resistance is associated with the increased expression of PGC1-α, which induce mitochondrial biogenesis. In summary, this study confirms that Sirt1 is a potential target for DLBCL treatment.

There is evidence that atypical antipsychotics (APs) increase risk of osteoporosis in schizophrenia patients, however the mechanism is unclear. The aim of the study was to explore the molecular mechanisms about Wnt/β-catenin signal pathway underlying the osteal side effects of APs.

TP53 mutation is an indicator of poor prognostic in chronic lymphocytic leukemia (CLL). Worse still, CLL patients with TP53 mutation are associated with poor efficacy to current chemotherapeutic, such as Fludarabine. Here, we confirmed that high expression of HDAC1 in CLL patients with TP53 mutation, which is closely related to poor prognosis and drug-resistance. Subsequently, we demonstrated Entinostat (HDAC1 inhibitor) combination with Fludarabine significantly induced apoptosis in TP53 mutations CLL cells. Its mechanism was associated with up-regulation of the pro-apoptotic protein Bax and the down-regulation of HDAC1, HO-1 and BCL-2 proteins. More importantly, we also confirmed that upregulation of HDAC1 could resistant Entinostat-induced apoptosis in TP53 mutations CLL cells by activating the HDAC1/P38/HO-1 pathway. In vivo, we found that Entinostat combination with Fludarabine significantly induced tumor cells apoptosis and prolong survival time in xenograft mouse model. Finally, combining vitro and vivo experiments, we presented the first demonstration that Entinostat combination with Fludarabine had a synergistic effect on the induction of apoptosis in TP53 mutations CLL cells. In conclusion, we provide valuable pre-clinical experimental evidence for the treatment of CLL patients with poor prognosis, especially for TP53 mutations.

Background and purpose: To investigate the SPARC expression and relationship with survival in Colorectal cancer (CRC) patients in Han, Buyi and Miao race. Methods: In our study, SPARC protein expression was detected in 90 available formalin-fixed paraffin-embedded (FFPE) tissues specimens from CRC patients in Han, Buyi and Miao race from the Third Affiliated Hospital of Guizhou Medical University by means of immunohistochemistry. According to the different expression of SPARC, the patients were divided into low expression group (SPARC score of 0+and 1+) and high expression group (SPARC score of 2+ and 3+). The correlations between the two groups in DFS and OS were analyzed, respectively. Results: SPARC was mainly expressed in tumor cell cytoplasm and the positive rates of SPARC was 52.2% (47/90). There was no difference in the positive expression rate in the Han, Buyi and Miao race (P =0.87). SPARC expression was related to the pathological type (Adenocarcinoma). There was a marked associations in DFS between the low expression of SPARC group and high expression group (P=0.048, 0.047) in the Han and Miao ethnic. While the same result was no found in the Buyi race (P=0.176). There was no statistical significance in OS between the low expression of SPARC group and high expression group in the Buyi, Miao and Han race, respectively(P= 0.338, 0.424, 0.282). Conclusion: SPARC was related with DFS in the Miao and Han race, while no correlation in the Buyi race.

Objective: To investigate the effect of lmna gene down-regulation on early hematopoietic development of zebrafish. Methods: Phosphorodiamidate morpholino oligomer ( PMO) technology was used to downregulate lmna gene expression in Zebrafish. Zebrafish embryos injected phosphorodiamidate morpholino antisense oligonucleotide of lmna gene mRNA by microinjection at unicellular stage were taken as the experimental group, and those injected meaningless phosphorodiamidate morpholino antisense oligonucleotide were taken as the control. The embryos were collected at 18, 24, 30 and 36 hpf after the fertilization. The real-time fluorescent quantitative PCR ( RT-PCR) and whole embryo in situ hybridization methods were used to detect the expression of myeloid hematopoietic transcription factor pu. 1 and erythroid hematopoietic transcription factor gata1 in zebrafish. Results:RT-PCR showed that the expressions of pu. 1 and gata1 decreased in the experimental group compared with the control group ( all P<0. 05 ) . Whole embryo in situ hybridization showed that the blue-black positive hybridization signals of pu. 1 and gata1 in experimental group were shallow than those in the control group. Conclusion: Myeloid hematopoietic and erythroid hematopoietic of zebrafish are blocked with the downregulation of lmna gene.