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.
Delineation of the Key Aspects in the Regulation of Epithelial Monolayer Formation
MOLECULAR AND CELLULAR BIOLOGY
Authors: Aschauer, Lydia; Gruber, Leonhard N.; Pfaller, Walter; Limonciel, Alice; Athersuch, Toby J.; Cavill, Rachel; Khan, Abdulhameed; Gstraunthaler, Gerhard; Grillari, Johannes; Grillari, Regina; Hewitt, Philip; Leonard, Martin O.; Wilmes, Anja; Jennings, Paul
Abstract
The formation, maintenance, and repair of epithelial barriers are of critical importance for whole-body homeostasis. However, the molecular events involved in epithelial tissue maturation are not fully established. To this end, we investigated the molecular processes involved in renal epithelial proximal-tubule monolayer maturation utilizing transcriptomic, metabolomic, and functional parameters. We uncovered profound dynamic alterations in transcriptional regulation, energy metabolism, and nutrient utilization over the maturation process. Proliferating cells exhibited high glycolytic rates and high transcript levels for fatty acid synthesis genes (FASN), whereas matured cells had low glycolytic rates, increased oxidative capacity, and preferentially expressed genes for beta oxidation. There were dynamic alterations in the expression and localization of several adherens (CDH1, -4, and -16) and tight junction (TJP3 and CLDN2 and -10) proteins. Genes involved in differentiated proximal-tubule function, cilium biogenesis (BBS1), and transport (ATP1A1 and ATP1B1) exhibited increased expression during epithelial maturation. Using TransAM transcription factor activity assays, we could demonstrate that p53 and FOXO1 were highly active in matured cells, whereas HIF1A and c-MYC were highly active in proliferating cells. The data presented here will be invaluable in the further delineation of the complex dynamic cellular processes involved in epithelial cell regulation.