MiRNA-203a-5p alleviates the malignant progression of Wilms' tumor via targeting JAG1.

OBJECTIVE: To uncover the potential influence of microRNA-203a-5p (miRNA-203a-5p) on the malignant progression of Wilms' tumor (WT). PATIENTS AND METHODS: MiRNA-203a-5p levels in 49 paired WT and paracancerous tissues were determined by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Prognostic value of miRNA-203a-5p in WT was assessed by the Kaplan-Meier method. Correlation between miRNA-203a-5p level and clinical data of WT patients was analyzed. In G401 and SK-NEP-1 cells, in vitro functions of miRNA-203a-5p in regulating metastatic abilities were explored. The interaction between miRNA-203a-5p and JAG1, and their regulatory role in the malignant progression of WT were evaluated by Dual-Luciferase reporter gene assay and rescue experiments. RESULTS: MiRNA-203a-5p was downregulated in WT tissues than that of paracancerous ones. WT patients expressing low level of miRNA-203a-5p had higher risk of lymphatic metastasis and worse prognosis. Overexpression of miRNA-203a-5p attenuated migratory and invasive abilities in G401 cells. On the contrary, knockdown of miRNA-203a-5p yielded the opposite trends in SK-NEP-1 cells. JAG1 was verified to be the direct gene binding miRNA-203a-5p, which was negatively regulated by miRNA-203a-5p in WT cells. Rescue experiments finally uncovered that miRNA-203a-5p alleviated the malignant progression of WT via negatively regulating JAG1. CONCLUSIONS: MiRNA-203a-5p is downregulated in WT and closely linked to lymphatic metastasis of WT patients. By negatively regulating JAG1, miRNA-203a-5p alleviates the malignant progression of WT.

Nuclear receptor subfamily 1 group H member 2 (LXRB) is the predominant liver X receptor subtype regulating transcription of 2 major lipogenic genes in goat primary mammary epithelial cells.

In ruminants, recent research has identified a crucial role for liver X receptors (LXR) in regulating lipid metabolism in mammary cells. However, the differences between LXR subtypes in regulating ruminant lipid metabolism are unknown. We used overexpression and knockdown of LXRA and LXRB in goat primary mammary epithelial cells to distinguish subtype-specific regulation of sterol regulatory element binding protein 1c (SREBP1c) and fatty acid synthase (FASN) mRNA expression and their promoter activity. Incubation with siRNA targeting LXR decreased expression of LXRA and LXRB. Knockdown of LXRA and LXRB in cells incubated with dimethyl sulfoxide (DMSO, control) had no effect on the expression of SREBP1c or FASN. Knockdown of LXRB in cells incubated with LXR ligand T0901317 (T09) led to decreased expression of FASN, but not SREBP1c. Overexpression of LXRB plus T09 dramatically upregulated SREBP1c and FASN to levels higher than overexpression of LXRA with T09. Luciferase reporter assays in cells with site-directed mutagenesis of LXR response elements (LXRE; LXRE1 from -286 to -251 bp or LXRE2 from -235 to -219 bp) revealed that the SREBP1c promoter with the wild type or either LXRE mutation in cells supplemented with T09 decreased markedly only when LXRB was knocked down. Knockdown of LXRA and LXRB had no effect on the SREBP1c promoter when cells had a double LXRE mutation. Overexpression of LXRA only in cells incubated with T09 increased the activity of the SREBP1c promoter with the wild type and the LXRE2 mutation. In contrast, compared with each control group, overexpression of LXRB dramatically increased SREBP1c promoter activity, regardless of LXRE mutation. Furthermore, in cells stimulated with T09, knockdown of either LXRA or LXRB did not alter wild-type FASN promoter activity. Knockdown of LXRA increased wild-type and LXRE-site-mutated (LXRE from -677 to -662 bp) FASN promoter activity. Overexpression of LXRB increased wild-type and LXRE-site-mutated FASN promoter activity regardless of treatment with DMSO or T09, but overexpression of LXRA altered LXRE-site-mutated FASN promoter activity only in cells treated with DMSO. Increased activation of SREBP1c or FASN promoters containing LXRE mutations after overexpression of LXRB suggested that LXRB activates endogenous SREBP1c, which can then bind to the promoter of SREBP1c via an auto-loop circuit regulatory mechanism. Collectively, these results highlight an important role for LXRB in the transcriptional regulation of SREBP1c and FASN in goat mammary epithelial cells. Activation of this nuclear receptor controls lipogenesis via different mechanisms.

Comparison of laparoscopic hernia repair and open herniotomy in children: a retrospective cohort study.

BACKGROUND: Laparoscopic hernia repair in infancy and childhood is still debatable. The objective of this study is to compare laparoscopic-assisted hernia repair (LH) versus open herniotomy (OH) as regards operative time, postoperative complications, recurrence rate, and contralateral metachronous hernia rate. METHODS: We analyzed all the patients with inguinal hernia who underwent surgery in our hospital from January 1, 2015 to December 31, 2015. There were 1125 patients, of which 202 patients received laparoscopic inguinal hernia repair (group A) and 923 patients received open herniotomy (group B). We recalled all the patients' records to identify operative time, postoperative hydrocele formation, and contralateral patent processus vaginalis (CPP) detection; we recalled all the patients' parents to identify the ipsilateral and contralateral recurrence and the testis position. RESULTS: During the study period, the lost to follow-up rate is 9.9% in group A and 14.1% in group B. The mean follow-up period was about 10.1 months. The mean operative time for females with bilateral hernia in group A was much shorter than that for those in group B (P = 0.001). The postoperative hydrocele formation rate in group A was 1.5%, compared with 8.2% in group B (P = 0.001). The recurrence rate was 0.64% in group A, whereas in group B the recurrence rate was 0.46%. Of patients with unilateral hernia, none in group A experienced a contralateral metachronous hernia (MH) compared with 10.1% in group B (P < 0.001) and 65% MH appeared in 3 months after the first hernia repair. Females and patients with initial left-sided hernia tended to have a contralateral MH after the first open hernia repair. CONCLUSION: Laparoscopic hernia repair in children is safe and effective, especially for female patients and patients with initial left-sided hernia. We recommend repairing the CPP simultaneously when performing laparoscopic procedures.

Down-regulation of BTG3 promotes cell proliferation, migration and invasion and predicts survival in gastric cancer.

BACKGROUND: Gastric cancer (GC) is one of the most common malignancies in China. B-cell translocation gene 3 (BTG3) has been identified as a tumor suppressor in several tumors, but its role in GC remains unknown. This study aimed to detect the expression of BTG3 and its prognostic value in GC tissues and determine its function in the progression of GC. METHODOLOGY: The expression of BTG3 was detected in GC cell lines and tissues by real-time RT-PCR, Western blot or immunohistochemistry. A series of in vitro and in vivo assays were performed to evaluate the effect of BTG3 on proliferation, migration and invasion of GC cells. RESULTS: B-cell translocation gene 3 was obviously down-regulated in GC tissues. Its expression was positively correlated with distant metastasis (P < 0.05). Patients with lower BTG3 expression had shorter overall survival time (P = 0.015). BTG3 suppressed the proliferation of GC cells in vitro and in vivo. It also inhibited migration and invasion of GC cells in vitro. CONCLUSION: Down-regulation of BTG3 is closely associated with proliferation, migration and invasion in GC. It may be a novel prognostic biomarker for GC patients.