PIM2 (proviral integration site for Moloney murine leukemia virus 2) kinase plays an important role as an oncogene in multiple cancers, such as leukemia, liver, lung, myeloma, prostate and breast cancers. PIM2 is largely expressed in both leukemia and solid tumors, and it promotes the transcriptional activation of genes involved in cell survival, cell proliferation, and cell-cycle progression. Many tumorigenic signaling molecules have been identified as substrates for PIM2 kinase, and a variety of inhibitors have been developed for its kinase activity, including SMI-4a, SMI-16a, SGI-1776, JP11646 and DHPCC-9. Here, we summarize the signaling pathways involved in PIM2 kinase regulation and PIM2 mechanisms in various neoplastic diseases. We also discuss the current status and future perspectives for the development of PIM2 kinase inhibitors to combat human cancer, and PIM2 will become a therapeutic target in cancers in the future.

Background Endometriosis is a chronic hormonal inflammatory disease characterized by the presence of endometrial tissue outside the uterus. Endometriosis often causes infertility, which brings physical and mental pain to patients and their families. Methods We examined the functions of heat shock factor 1 (HSF1) in endometriosis development through cell count assay, cell-scratch assay and clone formation experiments. We used quantitative real-time PCR (qRT-PCR) and Western blot (WB) to detect HSF1 expression. Glucose and lactate levels were determined using a glucose (GO) assay kit and a lactate assay kit. Furthermore, we used a HSF1 inhibitor-KRIBB11 to establish a mouse model of endometriosis. Results Our data demonstrated that HSF1 promoted endometriosis development. Interestingly, HSF1 enhanced glycolysis via up-regulating PFKFB3 expression in endometriosis cells, which was a key glycolysis enzyme. Consistently, the HSF1 inhibitor KRIBB11 could abrogate endometriosis progression in vivo and in vitro. Conclusions Findings indicate that HSF1 plays an important role in endometriosis development, which might become a new target for the treatment of endometriosis. Electronic supplementary material Supplementary data are available.

BackgroundEndometriosis is a chronic hormonal inflammatory disease characterized by the presence of endometrial tissue (glands and stroma) outside the uterus. Endometriosis seriously affects the physical health of women of childbearing age, often causes infertility, and affects the body and mind of patients and their families.MethodsWe examined the effect of HSF1 on endometriosis through cell count, scratch and clone formation experiments. We used real-time quantitative PCR and western blotting to detect the effect of HSF1 on mRNA and protein of endometriosis cells. Collect the cell culture medium and Glucose levels and lactate levels were determined using a glucose (GO) assay kit and a lactate assay kit. Furthermore, we established a mouse model of endometriosis, and the effect of HSF1 on endometriosis was observed by inhibiting HSF1 with KRIBB11 in the mice.ResultsHSF1 is highly expressed in endometriosis and plays an indispensable role in endometriosis development in both cell and animal studies. We found that HSF1 promotes endometriosis development and glucose consumption and lactic acid production. Further research showed that HSF1 functions in endometriosis by up-regulating PFKFB3, a key enzyme in glycolysis. And the HSF1 inhibitor KRIBB11 can abrogate all of the above experimental effects both in vivo and in vitro. ConclusionsOur study shows that HSF1 plays a significant role in the occurrence and development of endometriosis, which may become a new target for the treatment of endometriosis and provide a new idea for the clinical treatment of endometriosis.

Background Endometriosis is a chronic hormonal inflammatory disease characterized by the presence of endometrial tissue outside the uterus. Endometriosis often causes infertility, which affects the body and mind of patients and their families.Methods We examined the functions of heat shock factor 1 (HSF1) in endometriosis development through cell count, scratch and clone formation experiments. We used quantitative real-time PCR (qRT-PCR) and Western blot (WB) to detect the functions of HSF1 in endometriosis cells. Glucose and lactate levels were determined using a glucose (GO) assay kit and a lactate assay kit. Furthermore, we established a mouse model of endometriosis by using a HSF1 inhibitor-KRIBB11.Results Our study demonstrated that HSF1 was highly expressed in endometriosis, and promoted endometriosis development. Interestingly, we found that HSF1 promoted glycolysis in endometriosis cells. Further, HSF1 enhanced glycolysis by up-regulating PFKFB3 in endometriosis cells, which was a key enzyme in glucose metabolism. Moreover, the HSF1 inhibitor KRIBB11 could abrogate endometriosis progression in vivo and in vitro.Conclusions Findings indicate that HSF1 plays an important role in the development of endometriosis, which might become a new target for the treatment of endometriosis and provide a new idea for the clinical treatment of endometriosis.Electronic supplementary material Supplementary data are available.