MiR-18a affects hypoxia induced glucose metabolism transition in HT22 hippocampal neuronal cell line through the Hif1a gene.

Hypoxia can cause a variety of diseases, including ischemic stroke and neurodegenerative diseases. Within a certain range of partial pressure of oxygen, cells can respond to changes in oxygen. Changes in oxygen concentration beyond a threshold will cause damage or even necrosis of tissues and organs, especially for the central nervous system. Therefore, it is very important to find appropriate measures to alleviate damage. MiRNAs can participate in the regulation of hypoxic responses in various types of cells. MiRNAs are involved in regulating hypoxic responses in many types of tissues by activating the hypoxia-inducible factor (HIF) to affect angiogenesis, glycolysis and other biological processes. By analyzing differentially expressed miRNAs in hypoxia and hypoxia-related studies, as well as the HT22 neuronal cell line under hypoxic stress, we found that the expression of miR-18a was changed in these models. MiR-18a could regulate glucose metabolism in HT22 cells under hypoxic stress by directly regulating the 3'UTR of the Hif1a gene. As a small molecule, miRNAs are easy to be designed into small nucleic acid drugs, so this study can provide a theoretical basis for the research and treatment of nervous system diseases caused by hypoxia.

N-(2-Chloro-phen-yl)-1-phenyl-formamido 3-(2-nitro-phen-yl)propano-ate.

In the title mol-ecule, C(22)H(17)ClN(2)O(5), the nitro-substituted benzene ring makes a dihedral angle of 79.22 (1)° with the benzoyl ring and 53.03 (1)° with the chloro-substituted benzene ring. An intra-molecular C-H⋯O hydrogen bond occurs. The crystal structure features weak C-H⋯Cl and C-H⋯O inter-actions.

N-(4-Methyl-phen-yl)-N-{[(2-nitro-phen-yl)acet-yl]-oxy}benzamide.

In the title mol-ecule, C(22)H(18)N(2)O(5), the nitro-substituted benzene ring makes dihedral angles of 71.56 (1)° with the benzoyl ring and 16.28 (1)° with the methyl-substituted benzene ring. The crystal structure features C-H⋯O inter-actions, which generate chains.

Hypoxia-Induced Downregulation of miR-29 in Renal Tumor Cells Affects Collagen IV Subunit Expression through Multiple Sites.

Multiple tumor exacerbations and treatment procedures, such as extracellular matrix remodeling, metabolic reprogramming, immunological evasion, and resistance to chemotherapy and radiotherapy, are influenced by intratumoral hypoxia. It is becoming increasingly clear how hypoxia interacts with the extracellular matrix and how this affects the growth of cancer. We analyzed the published sequencing results of hypoxia-stressed mouse kidney tumor cells and found that the expression of miR-29b was significantly downregulated. There are several sites that are complementary to the miR-29 seed sequence in the 3' non-coding regions (3'UTRs) of various extracellular matrix-related genes, including collagen IV. We analyzed the sequences of the 3'UTRs of different subunits of collagen IV in different species and constructed the corresponding phylogenetic trees. We found that the 3'UTRs of Col4a1 and Col4a4 may have been subjected to particular evolutionary pressures. By cloning the 3'UTRs of collagen IV subunits into the psiCHECKTM-2 vector, we found that seven of the eight sites in the Col4a3-Col4a6 gene complementary to miR-29 were significantly repressed by miR-29a, b (except for the 7774-7781 of Col4a3 gene). The inhibitory efficiency of miR-29a, b on these seven sites was between 27% and 57%. The research on the regulation of miR-29 and extracellular matrix by hypoxia can provide a theoretical basis for tumor and fibrosis research and treatment.

Expression of NF-κB and PTEN in primary epithelial ovarian carcinoma and the correlation with chemoresistance.

The present study aims to investigate the relationship of NF-κB p65 and PTEN protein with chemotherapy resistance in ovarian cancer by measuring their expression in primary epithelial ovarian cancer, and to explore the correlation of the expression of these two proteins with ovarian carcinoma and their clinical significance. Ovarian cancer patients (n = 161) were divided into two groups: sensitive group (n = 82) and resistant group (n = 79). Expression of NF-κB p65 and PTEN protein in the ovarian cancer tissues was determined using immunohistochemistry to assess the relationship and correlation between the expression levels of these two proteins and chemotherapy resistance of ovarian carcinoma. The Cox model was used to analyze the independent risk factors associated with ovarian cancer prognosis. The expression of NF-κB p65 in the sensitive group (68.29%) was lower than that of the resistant group (94.94%). In contrast, the expression of PTEN protein in the sensitive group (50.00%) was higher than that of the resistant group (17.72%). Expression of NF-κB p65 was negatively correlated with that of PTEN protein in ovarian cancer tissue (rs = -0.246, P = 0.002). Expression of NF-κB p65 or PTEN protein and surgical stage of ovarian cancer were independent risk factors associated with chemoresistance (all P < 0.05). Low expression of PTEN and high expression of NF-κB are significant risk factors for chemotherapy resistance of ovarian cancer patients.

Chemoresistance is associated with Beclin-1 and PTEN expression in epithelial ovarian cancers.

The aim of the present study was to investigate the protein expression of the autophagy-related genes, BECN1 and PTEN, and the association with drug resistance in epithelial ovarian cancers. In total, 40 patients with pathologically diagnosed epithelial ovarian cancer were divided into a chemotherapy-sensitive group (n=20) and a chemotherapy-resistant group (n=20), according to the results of the pre- or post-operative normative chemotherapy and the post-operative follow-up. The protein expression of the phosphatase and tensin homolog (PTEN) and the BECN1 gene product, Beclin-1, was analyzed using immunohistochemistry in the 40 patients with ovarian carcinoma. The positive rate of Beclin-1 expression was significantly lower in the resistant group (35.0%) compared with the sensitive group (50.0%). The positive rate of PTEN expression was also significantly lower in the resistant group (30.0%) compared with the sensitive group (65.0%). Furthermore, the differences in the expression rates were revealed to be significant (P<0.05). The expression of Beclin-1 was identified to be positively correlated with the expression of PTEN (rs=0.816; P<0.0001). The low expression of the Beclin-1 and PTEN proteins in the ovarian cancer tissues was revealed to be closely associated with drug resistance. Therefore, Beclin-1 may interact with PTEN to participate in the mechanism of drug resistance and the changes in macrophage activity observed in cases of drug-resistant ovarian cancer.