Oxyquinoline-Dependent Changes in Claudin-Encoding Genes Contribute to Impairment of the Barrier Function of the Trophoblast Monolayer
BULLETIN OF EXPERIMENTAL BIOLOGY AND MEDICINE
Authors: Knyazev, E. N.; Petrov, V. A.; Gazizov, I. N.; Gerasimenko, T. N.; Tsypina, I. M.; Tonevitsky, A. G.; Sukhikh, G. T.
Abstract
Natural response to hypoxia critically depends on rapid stabilization of hypoxia-inducible factor (HIF). Under normoxic conditions, HIF-prolyl hydroxylases mark alpha-subunits of HIF for degradation, while hypoxia results in stabilization of HIF-alpha. Oxyquinoline derivatives suppress activity of HIF-prolyl hydroxylases leading to HIF activation in the cell. Here we show that 24-h incubation of BeWo b30 choriocarcinoma cells (a model of trophoblast in the placental barrier) with oxyquinoline derivative leads to a decrease in transepithelial electrical resistance (TEER) of the cell monolayer, while the permeability of the monolayer for FITC-dextran (70 kDa) remains unchanged. These findings suggest that the overall barrier function is preserved, while the structure of intercellular tight junctions can undergo minor changes. Using Affymetrix Human Transcriptome Array 2.0, we showed that the treatment with oxyquinoline derivative was followed by a decrease in the expression of claudins 6 and 7 (CLDN6, CLDN7), occludin (OCLN), contact adhesion molecule 3 (JAM3), and angiomotin-like protein 1 (AMOTL1).
The circ-AMOTL1/ENO1 Axis Implicated in the Tumorigenesis of OLP-Associated Oral Squamous Cell Carcinoma
CANCER MANAGEMENT AND RESEARCH
Authors: Liu, Jin; Yang, Qiaozhen; Sun, Hongying; Wang, Xiaxia; Saiyin, Hexige; Zhang, Hui
Abstract
Background: Oral squamous cell carcinoma (OSCC) may develop from a variety of oral potentially malignant disorders, but the mechanism of malignant transformation is still unknown. Among them, oral lichen planus (OLP) has a high prevalence. Previous studies have shown that a-enolase (ENO1) can promote cell proliferation and play an important role in tumorigenesis. In this study, we aim to explore the mechanism of ENO1 regulation in the process of OSCC tumorigenesis from OLP. Methods: ENO1 expression in tissues was determined by real-time quantitative PCR and immunohistochemistry. ENO1 was knocked down in cal-27 to observe the change in cell proliferation. Then, RNA-seq and bioinformatics analyses were conducted between OLP and OSCC samples. The expression of circ-AMOTL1, miRNA-22-3p, and miRNA-1294 was assessed using the real-time quantitative PCR. With knockdown and overexpression of circ-AMOTL1 in vitro, the change of ENO1 in the mRNA level was also assessed. Results: ENO1 was enhanced in the OSCC samples in comparison with OLP. Immunohistochemistry and real-time quantitative PCR results showed that ENO1 was significantly higher in OSCC tissue than in the OLP group, with a statistically significant difference (p<0.05). When ENO1 was knocked down in cal-27, cell proliferation was inhibited (p<0.05). The expression of miR-22-3p and miR-1294 was decreased in OSCC tissues, whereas ENO1 and circ-AMOTL1 increased. In an in vitro study, knockdown of circ-AMOTL1 resulted in a decrease of ENO1, while overexpression of circ-AMOTL1 led to an increase of ENO1 in the mRNA level. Conclusion: We confirmed that ENO1 expression was elevated in OSCC and increased cell proliferation. In an in vitro study, ENO1 expression was promoted by circ-AMOTL1. ENO1 may play a role as a tumor-promoting gene in OSCC through the circ-AMOTL1/miR-22-3p/miR-1294 network. These novel findings may shed further light on the pathogenesis from OLP to OSCC and the potential precursor markers.