[Role of microRNA-17-5p in the pathogenesis of pediatric nephrotic syndrome and related mechanisms].

OBJECTIVE: To study the role of microRNA-17-5p (miR-17-5p) in the pathogenesis of pediatric nephrotic syndrome (NS) and its effect on renal podocyte apoptosis via the activin A (ActA)/Smads pathway. METHODS: An analysis was performed on 55 children with NS (NS group) who were admitted from March 2018 to March 2019. Fifty healthy children who underwent physical examination during the same period of time were enrolled as the control group. The mRNA expression of miR-17-5p in peripheral blood was measured and compared between the two groups. Human renal podocytes were transfected with antisense oligonucleotide recombinant plasmid containing miR-17-5p (inhibition group) or control vector containing nonsense random sequence (negative control group), and untreated human renal podocytes were used as the blank group. These groups were compared in terms of cell apoptosis and the mRNA and protein expression of miR-17-5p, ActA, and Smads after transfection. RESULTS: The NS group had a significantly higher level of miR-17-5p in peripheral blood than the control group (P<0.001). Compared with the blank and negative control groups, the inhibition group had significantly lower apoptosis rate and relative mRNA expression of miR-17-5p and significantly higher relative mRNA and protein expression of ActA, Smad2, and Smad3 (P<0.001). CONCLUSIONS: There is an increase in the content of miR-17-5p in peripheral blood in children with NS. Low expression of miR-17-5p can inhibit the apoptosis of human renal podocytes, which may be associated with the upregulation of the mRNA and protein expression of ActA, Smad2 and Smad3.

10-HDA Induces ROS-Mediated Apoptosis in A549 Human Lung Cancer Cells by Regulating the MAPK, STAT3, NF-κB, and TGF-ß1 Signaling Pathways.

10-Hydroxy-2-decenoic acid (10-HDA), also known as royal jelly acid, has a variety of physiological functions, and recent studies have shown that it also has anticancer effects. However, its anticancer mechanisms have not been clearly defined. In this study, we investigated the underlying mechanisms of 10-HDA in A549 human lung cancer cells. We used Cell Counting Kit-8 assay, scratch wound healing assay, flow cytometry, and western blot analysis to investigate its apoptotic effects and underlying mechanism. Our results showed that 10-HDA inhibited the proliferation of three types of human lung cancer cells and had no significant toxic effects on normal cells. Accompanying reactive oxygen species (ROS), 10-HDA induced A549 cell apoptosis by regulating mitochondrial-associated apoptosis, and caused cell cycle arrest at the G0/G1 phase in a time-dependent manner. Meanwhile, 10-HDA also regulated mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3 (STAT3), and nuclear factor kappa B (NF-κB) signaling pathways by increasing the expression levels of phosphorylated c-Jun N-terminal kinase, p-p38, and I-κB, and additionally, by decreasing the expression levels of phosphorylated extracellular signal-regulated kinase, p-STAT3, and NF-κB. These effects were blocked by MAPK inhibitors and N-acetyl-L-cysteine. Furthermore, 10-HDA inhibited cell migration by regulating transforming growth factor beta 1 (TGF-ß1), SNAI1, GSK-3ß, E-cadherin, N-cadherin, and vimentin. Taken together, the results of this study showed that 10-HDA induced cell cycle arrest and apoptosis in A549 human lung cancer cells through ROS-mediated MAPK, STAT3, NF-κB, and TGF-ß1 signaling pathways. Therefore, 10-HDA may be a potential therapy for human lung cancer.

Expression of human leucocyte antigen G (HLA-G) is associated with prognosis in non-small cell lung cancer.

In a previous study, we demonstrated that human leucocyte antigen G (HLA-G) was aberrantly expressed in a majority of primary colorectal carcinomas, and that the detection of HLA-G expression had a strong and independent prognostic value in human colorectal cancer. In the current study, we look into whether the aberrant expression of HLA-G is also related to non-small cell lung cancer (NSCLC). The expression of HLA-G was investigated immunohistochemically in 106 patients with NSCLC. The correlation between HLA-G status and various clinicopathological parameters was analysed. As well, the level of HLA-G expression was also compared to the survival rate of patients with NSCLC. In total, we found that in 75% (79/106) of the primary site of NSCLC, an aberrant HLA-G expression was detected. However, this expression was not observed in the normal lung tissues. HLA-G expression in NSCLC was significantly correlated with lymph nodal metastasis, clinical stages of the disease, and host immune response (P = 0.0001, 0.0001, and 0.027, respectively). Patients with HLA-G positive tumours had a significantly shorter survival time than those with tumours that were HLA-G negative (P = 0.001). In addition, through multivariate analysis, HLA-G exhibited an independent prognostic factor (P = 0.01, relative risk 4.09; 95% confidence interval 1.40-11.9). All in all, our results indicate that the expression of HLA-G is a characteristic feature of NSCLC, and they suggest that immunostaining by anti-HLA-G antibodies may be a potentially useful prognostic indicator.

Expression of HLA-G is associated with prognosis in esophageal squamous cell carcinoma.

The detection of HLA-G expression might serve as a clinical marker in the diagnosis or prediction of clinical outcomes for certain types of carcinoma. The aim of this study was to determine whether the detection of HLA-G has any important clinical applications for patients with esophageal squamous cell carcinoma (ESCC) by using immunohistochemical methods. We observed that the HLA-G protein was expressed in 90.9% (110/121) of the primary sites of ESCC but not in the normal esophageal tissues. The expression of HLA-G in the tumors was significantly correlated with histologic grade, depth of invasion, nodal status, host immune response, and clinical stage of disease. Patients with positive HLA-G expression had a significantly worse prognosis. In multivariate analysis, HLA-G was an independent prognostic factor. Our results indicate that expression of HLA-G is a characteristic feature of ESCC and suggest that immunostaining by anti-HLA-G antibodies may be a potentially useful prognostic indicator.

Human leukocyte antigen G expression: as a significant prognostic indicator for patients with colorectal cancer.

Aberrant expression of human leukocyte antigen G (HLA-G) has been proposed to be involved in tumor escape mechanisms. It has been also proposed that detection of HLA-G might service as a potential biomarker for diagnosis or prediction of the clinical outcomes in ovarian and breast cancers, carcinoma of the lung and endometrial cancer. The aim of this current study is to determine if HLA-G is expressed in colorectal carcinomas and if the expression is associated with clinicopathological and prognostic data. The expression of HLA-G was investigated immunohistochemically in 201 patients with colorectal carcinomas. The correlation between HLA-G status, clinicopathological factors and the overall survival rate was analyzed. In this prospectively study, HLA-G protein expression was observed in 64.6% (130/201) of the primary site colorectal carcinomas, but not in the normal colorectal tissues or benign adenomas. HLA-G expression in the tumors was significantly correlated with the depth of invasion, histological grade, host immune response, lymph nodal metastasis and clinical stages of the disease (P=0.001, 0.0001, 0.002, 0.001 and 0.031, respectively). Patients with HLA-G positive tumors had a significantly shorter survival time than those patients with tumors that were HLA-G negative (P=0.0001). As well, in multivariate analysis, HLA-G demonstrated an independent prognostic factor (P=0.021, relative risk 3.14; 95% confidence interval, 1.34-8.10). Therefore, it can be gathered that HLA-G might serve as an independent prognostic factor for colorectal cancer patients.

Expression of human leukocyte antigen G (HLA-G) correlates with poor prognosis in gastric carcinoma.

OBJECTIVE: We had previously demonstrated that human leukocyte antigen G (HLA-G) was expressed in a majority of primary colorectal carcinomas and that the detection of HLA-G expression had a strong and independent prognostic value for that cancer. Currently, we investigate whether or not HLA-G is also expressed in patients with gastric carcinoma and whether the expression has any clinical application value. METHODS: The expression of HLA-G was investigated immunohistochemically in 160 patients with gastric carcinoma. The correlation between HLA-G status and various clinicopathological parameters was analyzed with the levels of HLA-G expression used to compare the survival length amongst patients. RESULTS: HLA-G protein expression was observed in 71% (113 of 160) of the primary site of gastric carcinomas, but not in the normal stomach tissues. HLA-G expression in the tumors was significantly correlated with the tumor location, histological grade, depth of invasion, lymph nodal metastasis, clinical stages of the disease, and host immune response (P = .012, .008, .001, .038, .030, and .016, respectively). Patients with HLA-G positive tumors had a significantly shorter survival time than those patients with tumors that were HLA-G negative (P = .001). As well, in multivariate analysis, HLA-G demonstrated an independent prognostic factor (P = .0001, relative risk 9.08; 95% confidence interval, 3.44-24.0). CONCLUSIONS: Overall, our results indicated that the expression of HLA-G is a characteristic feature of gastric carcinoma and that immunostaining by anti-HLA-G antibody may be a potentially useful prognostic indicator.