Search

Plant sense phosphate (Pi) deficiency and initiate signaling that controls adaptive responses necessary for Pi acquisition. Herein, evidence establishes that AtSIZI is a plant small ubiquitin-like modifier (SUMO) E3 ligase and is a focal controller of Pi starvation- dependent responses. T-DNA insertional mutated alleles of AtSIZ1 (At5g6041 0) cause Arabidopsis to exhibit exaggerated prototypical Pi starvation responses, including cessation of primary root growth, extensive lateral root and root hair development, increase in root/shoot mass ratio, and greater anthocyanin accumulation, even though intracellular Pi levels in sizi plants were similar to wild type. AtSIZI has SUMO S ligase activity in vitro, and immunoblot analysis revealed that the protein sumoylation profile is impaired in sizi plants. AtSIZI-GFP was localized to nuclear foci Steady- state transcript abundances of Pi starvation-responsive genes AtPT2, AtPS2, and AtPS3 were moderate but clearly greater in sizi seedlings than in wild type, where Pi is sufficient. Pi starvation induced the expression of these genes to the same extent in sizi and wild-type seedlings. However, two other Pi starvation-responsive genes, AtIPS1 and AtRNSI, are induced more slowly in sizi seedlings by Pi limitation. PHRI, a MYB transcriptional activator of AtIPSI and AtRNSI, is an AtSIZI sumoylation target. These results indicate that AtSIZI is a SUMO E3 ligase and that sumoylation is a control mechanism that acts both negatively and positively on different Pi deficiency responses. [ABSTRACT FROM AUTHOR]

PIWIL2-like (PL2L) protein 60 (PL2L60), a product of aberrantly activated PIWIL2 gene, is widely expressed in various types of tumors and may promote tumorigenesis. However, the mechanisms underlying the activation of expression of PL2L60 remain unknown. In this study, an intragenic promoter responsible for the activation of PL2L60 within the human PIWIL2 gene has been identified, cloned and characterized. The promoter of PL2L60 is located in the intron 10 of the host gene PIWIL2. Bioinformatic and mutagenic analysis reveals that this intragenic promoter within the sequence of 50 nucleotides contains two closely arranged cis-acting elements specific for the hepatic leukemia factor (HLF) in the positive strand and signal transducer and activator of transcription 3 (STAT3) in the negative strand. Chromatin immunoprecipitation analysis demonstrates that both the HLF and polymerase II (Pol II), a hallmark of active promoters, directly bind to the sequence, although STAT3 does not. Knockdown of HLF and STAT3 alone or both by RNA interference significantly reduced both promoter activity and the PL2L60 protein expression, although there is no additive effect. The expression of PL2L60 proteins was enhanced when host gene Piwil2 was genetically disrupted in a murine cell model. Taken together, we have identified a PL2L60-specific intragenic promoter in the host gene of PIWIL2, which is interdependently activated by HLF and STAT3 through steric interaction. This activation is dependent on cellular milieu rather than the integrity of host gene PIWIL2, highlighting a novel, important mechanism for a cancer-causing gene to be activated during tumorigenesis.

Background: Metformin is the first line of oral antidiabetic drug in the biguanide class for treatment of type 2 diabetes. Increasing evidence has suggested that it is a potential anti-tumor drug. However, the mechanisms underlying inhibiting tumor development remain elusive, especially in bladder tumors., Methods: T24 and J82 cell lines were used as an in vitro model, and 24 female SD rats were used to build an N-methyl-N-nitrosourea (MNU)-induced orthotopic rat bladder cancer model. Transfection of lentivirus-based shRNA was used to construct the STAT3-KNOCKDOWN T24 cell line. After metformin treatment, the viability of bladde cancer cells was determined by CCK8. Cell cycle distribution and apoptosis were assessed by flow cytometry. The migration and invasion abilities of cells were evaluated by wound healing and transwell asssays. The inactivation of stat3 pahtway was examined by qRTPCR, western blot and Immunofluorescence., Results: Metformin can effectively inhibit precancerous progression to invasive cancer in an MNU-induced rat orthotopic bladder tumor model, although it could not completely suppress normal cells transforming into tumor cells. While the MNU could induce 50 % rats (4/8) to develop invasive bladder cancers, the rats co-administrated with metformin failed to develop invasive tumors but retained at precancerous or non-invasive stages, exhibiting as dysplasia, papillary tumor and/or carcinoma in situ (CIS). Accordingly, phosphorylation of signal transducer and activator of transcription 3 (STAT3), which is a well known oncogene, was significantly inhibited in the tumors of rats treated with metformin. In vitro experiments revealed that the metformin could efficiently inhibit STAT3 activation, which was associated with the cell cycle arrest, reduction of cell proliferation, migration and invasiveness, and increase in apoptotic cell death of bladder cancer cell lines., Conclusions: These findings provide for the first time the evidence that metformin can block precancerous lesions progressing to invasive tumors through inhibiting the activation of STAT3 pathway, and may be used for treatment of the non-invasive bladder cancers to prevent them from progression to invasive tumors.

Background: Mucinous tubular and spindle cell carcinoma of kidney (MTSCC-K) is a rare variant of renal tumor. The current data show most of MTSCCs are of low malignant potential and rare cases metastatic to lymph nodes have been reported; however, the recorded computed tomography (CT) and follow up data are limited., Material and Method: In the present study, we retrospectively analyzed CT and clinicopathological data of eight patients with renal MTSCC-K., Results: A total of eight cases, including six females and two males, were included in this analysis with a mean age of 48.4 (range 25 to 81) years. Mean tumor size was 4.2 (range 2.5 to 10.0) cm. Preoperative CT demonstrated that all tumors were slightly enhanced on both corticomedullary and nephrographic phase, which was different from many other renal cell carcinomas. Three of them were treated with open radical nephrectomy, three with laparoscopic radical nephrectomy and the other two with laparoscopic partial nephrectomy. No postoperative therapy was applied. Patients were followed up for 15 to 64 months and there was no evidence of recurrence and metastasis., Conclusions: The MTSCC-K has special clinicopathological characteristics, low degree of malignancy and relative good prognosis. The diagnosis mainly depends on the histopathological examination and CT may help to differentiate with papillary renal cell carcinoma. Surgical treatment is recommended and additional therapies are not necessary., Virtual Slides: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8435581771088249.

Testicular seminoma has become the most common solid malignancy in young men, especially in the 20s group. We obtained the gene expression profile of human testicular seminoma cells from NCBI, identified the differentially expressed genes of testicular seminoma cells of different stages, and constructed the regulation networks of different stages of testicular seminoma using bioinformatics methodology. Forty differentially expressed genes of testicular seminoma cells of different stages were identified. These genes and pathways are apparently involved in the progression of testicular seminoma.

Prostate cancer is one of the most common malignancies in men. Previous research has determined that androgen deprivation therapy (ADT) may be accompanied by an unfavourable metabolic profile. In this prospective study, 133 men were recruited, including 46 prostate cancer patients who had undergone bilateral orchiectomy and been on flutamide (the ADT group), 37 men with prostate cancer who had undergone radical prostatectomy (the non-ADT group) and 50 normal control subjects (the control group). All subjects were followed for at least 12 months. From baseline to 3 months, men in the ADT group had increased levels of fasting serum insulin and low-density lipoprotein compared to the other two groups (P<0.05). No obvious changes were found in the other parameters (P>0.05). After 12 months, men in the ADT group had increased levels of waist circumference, fasting serum insulin and glucose, total cholesterol, high-density lipoprotein and low-density lipoprotein compared to the other two groups (P<0.05). Additionally, the morbidity rate of metabolic syndrome in the ADT group was higher (P<0.05) compared to the other two groups. ADT through surgical castration for men with prostate cancer may be associated with unfavourable metabolic changes. The benefits of the therapy should be balanced prudently against these risks.