Yue Zhao1, Kaicheng Xu2, Peng Liu3. 1. Department of Vascular Surgery, China-Japan Union Hospital, Jilin University, Changchun, China. 2. Department of Anesthesiology, China-Japan Union Hospital, Jilin University, Changchun, China. 3. Department of Orthopaedics, China-Japan Union Hospital, Jilin University, Changchun, China.
Abstract
BACKGROUND/AIMS: MicroRNAs (miRNAs) play an essential role in the tumorigenesis of osteosarcoma (OS). However, the effects of miR-1248 on chemo-resistant potential of OS have not been studied. Here, we addressed this question. METHODS: The levels of miR-1248 and apoptotic protein angiotensin II type 1 receptor (AGTR1) in OS specimens were examined by RT-qPCR and Western blotting, respectively. The relationship between miR-1248 and AGTR1 was determined by analysis of Spearman's Rank Correlation Coefficients. The patient survival was determined with Kaplan-Meier curves. Bioinformatics analyses were done to predict microRNAs (miRNAs) that target AGTR1. The functional binding of miRNAs to AGTR1 mRNA was examined by a dual luciferase reporter assay. Cell viability was determined by an CCK-8 assay. Apoptosis was determined by a fluorescence-based apoptosis assay. RESULTS: The levels of miR-1248 were significantly elevated while the levels of AGTR1 were significantly decreased in OS specimens than in paired adjacent normal tissue. The levels of miR-1248 were negatively correlated to the levels of AGTR1. Moreover, the patients with high miR-1248 levels had poorer survival than those with low MiR-1248 levels, and the patients with low AGTR1 levels had poorer survival than those with high AGTR1 levels. MiR-1248 inhibited protein translation of AGTR1, through binding to the 3'-UTR of the AGTR1 mRNA. The AGTR1-mediated cell apoptosis was suppressed by overexpressing miR-1248, and was augmented by depleting miR-1248. CONCLUSION: Increased miR-1248 expression in OS may inhibit AGTR1-mediated cancer cell death in chemotherapy. The outcome of chemotherapy may be improved by the suppression of miR-1248 in OS cells.
BACKGROUND/AIMS: MicroRNAs (miRNAs) play an essential role in the tumorigenesis of osteosarcoma (OS). However, the effects of miR-1248 on chemo-resistant potential of OS have not been studied. Here, we addressed this question. METHODS: The levels of miR-1248 and apoptotic protein angiotensin II type 1 receptor (AGTR1) in OS specimens were examined by RT-qPCR and Western blotting, respectively. The relationship between miR-1248 and AGTR1 was determined by analysis of Spearman's Rank Correlation Coefficients. The patient survival was determined with Kaplan-Meier curves. Bioinformatics analyses were done to predict microRNAs (miRNAs) that target AGTR1. The functional binding of miRNAs to AGTR1 mRNA was examined by a dual luciferase reporter assay. Cell viability was determined by an CCK-8 assay. Apoptosis was determined by a fluorescence-based apoptosis assay. RESULTS: The levels of miR-1248 were significantly elevated while the levels of AGTR1 were significantly decreased in OS specimens than in paired adjacent normal tissue. The levels of miR-1248 were negatively correlated to the levels of AGTR1. Moreover, the patients with high miR-1248 levels had poorer survival than those with low MiR-1248 levels, and the patients with low AGTR1 levels had poorer survival than those with high AGTR1 levels. MiR-1248 inhibited protein translation of AGTR1, through binding to the 3'-UTR of the AGTR1 mRNA. The AGTR1-mediated cell apoptosis was suppressed by overexpressing miR-1248, and was augmented by depleting miR-1248. CONCLUSION: Increased miR-1248 expression in OS may inhibit AGTR1-mediated cancer cell death in chemotherapy. The outcome of chemotherapy may be improved by the suppression of miR-1248 in OS cells.
Authors: G M Viera; K B Salomao; G R de Sousa; M Baroni; L E A Delsin; J A Pezuk; M S Brassesco Journal: Clin Transl Oncol Date: 2019-04-04 Impact factor: 3.405
Authors: Giuseppina Catanzaro; Zein Mersini Besharat; Andrea Carai; Natalie Jäger; Elena Splendiani; Carole Colin; Agnese Po; Martina Chiacchiarini; Anna Citarella; Francesca Gianno; Antonella Cacchione; Evelina Miele; Francesca Diomedi Camassei; Marco Gessi; Luca Massimi; Franco Locatelli; David T W Jones; Dominique Figarella-Branger; Stefan M Pfister; Angela Mastronuzzi; Felice Giangaspero; Elisabetta Ferretti Journal: Biomark Res Date: 2022-06-17