Guo-Hua Gong1,2,3, Feng-Mao An1,2, Yu Wang1,2, Ming Bian1,2, Di Wang1,2, Cheng-Xi Wei4,5. 1. Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao, China. 2. Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, China. 3. First Clinical Medical of Inner Mongolia University for Nationalities, Tongliao, China. 4. Medicinal Chemistry and Pharmacology Institute, Inner Mongolia University for the Nationalities, Tongliao, Chinaweichengxi1226@163.com. 5. Inner Mongolia Key Laboratory of Mongolian Medicine Pharmacology for Cardio-Cerebral Vascular System, Tongliao, Chinaweichengxi1226@163.com.
Abstract
BACKGROUND/AIMS: Temporal lobe epilepsy (TLE) is the most common form of adult localization-related epilepsy that is accompanied by progressive etiopathology and high incidences of drug resistance. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression, however, the expression profile and clinical significance of circRNAs in TLE remains unknown. METHODS: Circular RNA microarray was conducted to identify TLE-related circRNAs. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in TLE in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in TLE cell. RESULTS: 586 differentially expressed circRNAs were identified between TLE and the control tissues. The expression of circRNA-0067835 was significantly down-regulated in tissues and plasma from TLE patients. Lower circRNA-0067835 correlated to increased seizure frequency, HS, and higher Engel's score. Overexpression of circRNA-0067835 observably decreased SH-SY5Y cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay. CONCLUSION: Our experiments showed that circRNA-0067835 regulated refractory epilepsy progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with TLE.
BACKGROUND/AIMS: Temporal lobe epilepsy (TLE) is the most common form of adult localization-related epilepsy that is accompanied by progressive etiopathology and high incidences of drug resistance. Circular RNAs (circRNAs) play important roles in fine-tuning gene expression, however, the expression profile and clinical significance of circRNAs in TLE remains unknown. METHODS: Circular RNA microarray was conducted to identify TLE-related circRNAs. CCK8 assays and flow cytometric assays were conducted to clarify the role of circRNA in TLE in vitro. Bioinformatics analysis and in vitro experiments were conducted to clarify the mechanism of circRNA-mediated gene regulation in TLE cell. RESULTS: 586 differentially expressed circRNAs were identified between TLE and the control tissues. The expression of circRNA-0067835 was significantly down-regulated in tissues and plasma from TLEpatients. Lower circRNA-0067835 correlated to increased seizure frequency, HS, and higher Engel's score. Overexpression of circRNA-0067835 observably decreased SH-SY5Y cell proliferation by causing G1 arrest and promoting apoptosis. Bioinformatics online programs predicted that circRNA-0067835 acted as miR-155 sponge to regulate FOXO3a expression, which was validated using luciferase reporter assay. CONCLUSION: Our experiments showed that circRNA-0067835 regulated refractory epilepsy progression by acting as a sponge of miR-155 to promote FOXO3a expression, indicating that circRNA-0067835 may serve as a potential therapeutic target for patients with TLE.
Authors: Morten T Venø; Cristina R Reschke; Gareth Morris; Niamh M C Connolly; Junyi Su; Yan Yan; Tobias Engel; Eva M Jimenez-Mateos; Lea M Harder; Dennis Pultz; Stefan J Haunsberger; Ajay Pal; Janosch P Heller; Aoife Campbell; Elena Langa; Gary P Brennan; Karen Conboy; Amy Richardson; Braxton A Norwood; Lara S Costard; Valentin Neubert; Federico Del Gallo; Beatrice Salvetti; Vamshidhar R Vangoor; Amaya Sanz-Rodriguez; Juha Muilu; Paolo F Fabene; R Jeroen Pasterkamp; Jochen H M Prehn; Stephanie Schorge; Jens S Andersen; Felix Rosenow; Sebastian Bauer; Jørgen Kjems; David C Henshall Journal: Proc Natl Acad Sci U S A Date: 2020-06-24 Impact factor: 11.205
Authors: Andreia Gomes-Duarte; Sebastian Bauer; Morten T Venø; Braxton A Norwood; David C Henshall; Jørgen Kjems; Felix Rosenow; Vamshidhar R Vangoor; R Jeroen Pasterkamp Journal: Front Genet Date: 2021-01-28 Impact factor: 4.599