Vertebrate Animal Models Unravel Physiological Roles for Zonula Occludens Tight Junction Adaptor Proteins
MOLECULAR STRUCTURE AND FUNCTION OF THE TIGHT JUNCTION: FROM BASIC MECHANISMS TO CLINICAL MANIFESTATIONS
Authors: Hunziker, Walter; Kiener, Tania K.; Xu, Jianliang
Abstract
Tight junctions (TJs) contribute to the maintenance of epithelial cell polarity and endothelial and epithelial barrier functions. Structurally, TJs are composed of integral membrane proteins, which are tethered to the actin cytoskeleton through adaptor or scaffolding proteins. Three related members of the membrane associated guanylate kinase (MAGUK) protein family-ZO-1, ZO-2, and ZO-3-have been extensively studied in cell culture systems, yet their relevance to TJ structure and function have only recently started to be elucidated. Vertebrate animal models-in particular, mouse and zebrafish-have contributed to the unraveling of the physiological importance of these proteins in vivo. Here we discuss recent findings on the importance of ZO-2 in mouse development and the role of ZO-3 in barrier function of the skin of zebrafish embryos.
Long non-coding RNA NEAT1 promotes ovarian cancer cell invasion and migration by interacting with miR-1321 and regulating tight junction protein 3 expression
MOLECULAR MEDICINE REPORTS
Authors: Luo, Min; Zhang, Lei; Yang, Hongying; Luo, Kaili; Qing, Chen
Abstract
Previous studies have reported that long non-coding RNAs (lncRNAs) have a significant role in the metastasis of tumors, including ovarian cancer (OC). The aim of the present study was to demonstrate the function and working mechanism of lncRNA nuclear enriched abundant transcript 1 (NEAT1) in OC. The expressions of NEAT1 in OC were measured by reverse transcription-quantitativePCR (RT-qPCR). The effects of NEAT1 on cell proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) were detected by Cell Counting Kit-8, transwell and wound healing assays, and western blotting. Dual-luciferase reporter assays were performed to confirm the correlated between NEAT and miR-1321, miR-1321 and TJP3. The effect of NEAT1 on miR-1321 and TJP3 was confirmed by RT-qPCR and western blotting. Elevated expression of NEAT1 was observed in OC cell lines, and NEAT1 expression was found to be positively related to the expression of tight junction protein 3 (TJP3), which is important in cancer development. Moreover, the present results indicated that NEAT1 and TJP3 expression levels were negatively correlated with microRNA (miR)-1321 expression in OC. Knockdown of NEAT1 attenuated the migration and invasion of OC cells, as well as increased miR-1321 expression and in turn led to the reduction of TJP3. Thus, the present study demonstrated that NEAT1 regulates TJP3 expression by sponging miR-1321 and enhances the epithelial-mesenchymal transition, invasion and migration of OC cells. Overall, the present study identified the function and mechanism of NEAT1 in OC, suggesting that NEAT1 may be a promising therapeutic target for OC metastasis.